SARS-CoV-2 and COVID-19 (29...)

Dit is een voortzetting van het onderwerp SARS-CoV-2 and COVID-19 (28...).

Dit onderwerp werd voortgezet door SARS-CoV-2 and COVID-19 (30...).

DiscussiePro and Con

Sluit je aan bij LibraryThing om te posten.

SARS-CoV-2 and COVID-19 (29...)

1margd
apr 18, 2022, 11:19 am

Prof. Akiko Iwasaki (Yale) @VirusesImmunity | 12:33 PM · Apr 16, 2022:
https://twitter.com/VirusesImmunity/status/1515367851296763911

A Phase 2 clinical trial of oral camostat mesylate during early phase of COVID-19 in outpatients reduced illness course (including fatigue) and prevented loss of smell and taste! Work of fantastic colleagues at @YaleMed .* (1/)

This randomized double-blind placebo-controlled phase 2 trial gave patients (within 3 days of testing PCR+) either oral camostat mesylate or placebo pills, 4x/day for 7 days. Note the lower smell/taste scores (meaning better ability to smell and taste) in camostat group (2/)
Graphs-Smell/taste days after enrollment ( https://twitter.com/VirusesImmunity/status/1515367841498861574/photo/1 )

Camostat mesylate blocks TMPRSS2, which cleaves the spike protein allowing the virus to fuse with the cell and start to replicate. However, there was no differences in detectable viral RNA levels in patients treated with camostat vs. placebo in nasopharyngeal swab or saliva. (3/)
Graphs-viral load/day ( https://twitter.com/VirusesImmunity/status/1515367847110787079/photo/1 )

So how does camostat prevent loss of smell? It is possible that the drug blocks infection of specific types of cells, such as the sustentacular cells (supporting cells of olfactory sensory neurons) which express high levels of ACE2 and TMPRSS2. (4/)
Infographic ( https://twitter.com/VirusesImmunity/status/1515367851296763911/photo/1 )
fr Butowt et al 2021 ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488171/ )

Another possibility is that camostat may have lead to reduced inflammation within the olfactory system, reducing the damage caused by inflammation. Here is a nice write up of how inflammation is linked to loss of smell & #LongCovid 👇🏽 (5/)
Lloyd/Sci Am 2022 ( https://www.scientificamerican.com/article/covid-smell-loss-and-long-covid-linke... )

A nice description of the work by Geoffrey Chupp et al., with interviews with the authors and implications are discussed in this @YaleMedicine
piece here. (6/)
MacMillan 2022 ( https://www.yalemedicine.org/news/prevent-loss-smell-covid )

Lastly, loss of sense of smell & taste after SARS-CoV-2 infection is debilitating. If an early treatment can prevent this from happening, it is encouraging news. We also need a treatment to help those who already have it. (end)
--------------------------------------------------------------------

Geoffrey Chupp et al. 2022. A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste. MedRxiv Jan 31, 2022. doi: https://doi.org/10.1101/2022.01.28.22270035 https://www.medrxiv.org/content/10.1101/2022.01.28.22270035v1

Abstract
...Results Participants receiving camostat had statistically significant lower quantitative symptom scores (FLU-Pro-Plus) at day 6, accelerated overall symptom resolution and notably improved taste/smell, and fatigue beginning at onset of intervention in the camostat mesylate group compared to placebo. Intention-to-treat analysis demonstrated that camostat mesylate was not associated with a reduction in 4-day log10 NP viral load compared to placebo.

Conclusions and relevance The camostat group had more rapid resolution of COVID-19 symptoms and amelioration of the loss of taste and smell. Camostat compared to placebo was not associated with reduction in nasopharyngeal SARS-COV-2 viral load. Additional clinical trials are warranted to validate the role of camostat mesylate on SARS-CoV-2 infection in the treatment of mild COVID-19.

...DISCUSSION
In this randomized, double-blind, placebo-controlled Phase 2 trial, a 7-day course of oral camostat mesylate given early in COVID-19 did not achieve the primary endpoint of reducing upper respiratory SARS-CoV-2 viral load compared to placebo. However, despite a relatively small sample size, we discovered a clinically-relevant effect of camostat on certain prespecified secondary outcomes. Using a high-resolution scoring system, FLU-PRO-Plus, that included
quantification of the perception of smell and taste in addition to standard clinical symptomatology measures of influenza, we found that camostat mesylate accelerated overall COVID-19 symptom resolution and prevented the loss of smell and taste.

...The important patient-focused, patient-reported symptomatic outcomes of camostat mesylate in early COVID-19 point to a need for further clinical trial testing. Important outcomes include determination whether this drug reduces risk for severe disease and hospitalization; synergizes with direct antiviral drugs; might be useful in post-exposure prophylaxis; and might be applicability to modulating symptoms in long COVID-19. The potential importance of an oral treatment for early COVID-19, with an inexpensive, repurposed drug with few side effects, and which reduces the risk of complications cannot be overstated in the context of the ongoing pandemic.

2margd
apr 18, 2022, 11:58 am

Eric Feigl-Ding (epidemiologist) @DrEricDing | 9:12 PM · Apr 15, 2022:
https://twitter.com/DrEricDing/status/1515136001592729601

📉PRECIPITOUS DROP in US life expectancy—a net loss of 2.26 years from 2019 to 2021 due to the pandemic. In contrast, peer countries performed much better—widening the gap in life expectancy between the US and peer countries to more than **5 years**! *
Fig 1 ( https://twitter.com/DrEricDing/status/1515136001592729601/photo/2 )
Fig 2 ( https://twitter.com/DrEricDing/status/1515136001592729601/photo/1 )

2) US life expectancy decreased from 78.86 years in 2019 to 76.99 years in 2020 and 76.60 years in 2021, a net loss of 2.26 years. In contrast, peer countries averaged a smaller decrease in life expectancy between 2019-2020 (0.57 years) and a 0.28-year increase for 2020-2021

3) The decrease in US life expectancy was highly racialized: whereas the largest decreases in 2020 occurred among Hispanic and non-Hispanic Black populations, in 2021 only the non-Hispanic White population experienced a decrease in life expectancy.
Graph-changes in life expectancy by race ( https://twitter.com/DrEricDing/status/1515136435757670402/photo/1 )

---------------------------------------------------------

* Ryan K. Masters et al. 2022. CHANGES IN LIFE EXPECTANCY BETWEEN 2019 AND 2021: UNITED STATES AND 19 PEER COUNTRIES. MedRxiv April 17, 2022. doi: https://doi.org/10.1101/2022.04.05.22273393 https://medrxiv.org/content/10.1101/2022.04.05.22273393v1

This article is a preprint and has not been peer-reviewed what does this mean?. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

ABSTRACT
...RESULTS US life expectancy decreased from 78.86 years in 2019 to 76.99 years in 2020 and 76.60 years in 2021, a net loss of 2.26 years. In contrast, peer countries averaged a smaller decrease in life expectancy between 2019 and 2020 (0.57 years) and a 0.28-year increase between 2020 and 2021, widening the gap in life expectancy between the United States and peer countries to more than five years. The decrease in US life expectancy was highly racialized: whereas the largest decreases in 2020 occurred among Hispanic and non-Hispanic Black populations, in 2021 only the non-Hispanic White population experienced a decrease in life expectancy.

DISCUSSION The US mortality experience during 2020 and 2021 was more severe than in peer countries, deepening a US disadvantage in health and survival that has been building for decades. Over the two-year period between 2019 and 2021, US Hispanic and non-Hispanic Black populations experienced the largest losses in life expectancy, reflecting the legacy of systemic racism and inadequacies in the US handling of the pandemic. Reasons for the crossover in racialized outcomes between 2020 and 2021, in which life expectancy decreased only in the non-Hispanic White population, could have multiple explanations.

3margd
apr 18, 2022, 4:33 pm

The case for testing Pfizer's Paxlovid for treating long COVID
Julie Steenhuysen | April 18, 2022

CHICAGO, April 18 (Reuters) - Reports of two patients who found relief from long COVID after taking Pfizer Inc's (PFE.N) antiviral Paxlovid, including a researcher who tested it on herself, provide intriguing evidence for clinical trials to help those suffering from the debilitating condition, experts and advocates say.

The researcher said her chronic fatigue symptoms, which "felt like a truck hit me," are gone after taking the two-drug oral therapy...

...(Dr. Steven Deeks, a professor of medicine at the University of California, San Francisco (USSF))...has heard of yet another anecdotal case at UCSF in which a long COVID patient's symptoms cleared after taking Paxlovid.

Scientists caution that these cases are "hypothesis-generating only" and not proof that the drug caused relief of lingering symptoms. But they lend support to a leading theory that long COVID may be caused by the virus persisting in parts of the body for months, affecting patients' daily lives long after acute symptoms disappear...

https://www.reuters.com/business/healthcare-pharmaceuticals/case-testing-pfizers...

4margd
Bewerkt: apr 19, 2022, 7:24 am

Mizelle, whose husband worked for Trump Admin and was friends with Stephen Miller, was declared unqualified by the ABA, but nominated by Trump nonetheless--after Election Day?

A federal judge strikes down the mask mandate on planes and public transit.
The move comes less than a week after the Centers for Disease Control and Prevention extended it through May.
Charlie Savage and Heather Murphy | April 18, 2022

WASHINGTON — A federal judge in Florida struck down the federal mask requirement on airplanes, trains, buses and other public transportation on Monday, less than a week after the Centers for Disease Control and Prevention had extended it through May 3.

In a 59-page decision, Judge Kathryn Kimball Mizelle, an appointee of former President Donald J. Trump, voided the mandate — which also applies to airports, train stations, and other transportation hubs — nationwide on several grounds, including ruling that the agency had exceeded its legal authority under the Public Health Services Act of 1944...

...Judge Mizelle had personal ties to the Trump administration...

https://www.nytimes.com/2022/04/18/us/politics/federal-mask-mandate-airplanes.ht...
-----------------------------------------------------------
ETA

Word is Biden Admin will have to fight ruling even though it's mandate had only a couple weeks left. Otherwise precedent may prevent CDC from issuing orders for the next public health emergency... Mizelle clerked for Clarence Thomas...

Laurence Tribe (Harvard Law) tribelaw | 11:41 PM · Apr 18, 2022:
She did it without even an oral argument! No wonder she earned a really rare ABA rating of “unqualified” to be a federal judge. Her opinion is a shambles, filled with unsupported medical claims as though she were an expert in fields about which she knows even less than about law!

5margd
apr 19, 2022, 6:58 am

Omicron lineages & sublineages:

BA.2.12.1 (ne US) has spike mutation L452Q (transmissibility?) on top of BA.2 background (immune escape).

BA.4 and BA.5 (S Africa) share spike mutations L452R (transmissibility in Delta), F486V (additional immune escape?) and reversion Q493R ("not obviously a key antigenic mutation").

"Looking forward, I expect these 452R/Q sublineages to continue to expand. As they do so, they may acquire additional mutations with the "winning" sublineage the one that accumulates the best constellation of mutations. 15/17"

"However, it's also possible for some other mutational constellation to arise (on top of BA.2 or otherwise) and overtake these new 452R/Q lineages. 16/17"

"This sort of accumulation of mutations that drive further host adaptation and antigenic drift is my general expectation for evolution in the coming months. It's possible we may have additional "Omicron-like" events, but my baseline is this steady "flu-like" scenario. 17/17"
--------------------------------------------

Trevor Bedford (scientist, Fred Hutchinson) @trvrb | 4:11 PM · Apr 18, 2022:
https://twitter.com/trvrb/status/1516147488587075584

We're now starting to see the evolution of new potentially impactful sublineages of Omicron with particular focus on mutations at spike residue 452. Here, I'd like to highlight lineages B.2.12.1 in New York, as well as BA.4 and BA.5 in South Africa. 1/17

Stepping back, Omicron emerged as three distinct lineages BA.1, BA.2 and BA.3 and despite the head start of BA.1, we've seen BA.2 overtake BA.1 across the world over the course of January to April. 2/17
https://twitter.com/trvrb/status/1516147494010253318/photo/1

Variant "fitness" will depend on intrinsic transmissibility and escape from existing population immunity. The first tranche of variants (Alpha, Delta, etc...) largely spread due to increased intrinsic transmissibility, while Omicron spread primarily due to immune escape. 3/17

BA.2's advantage over BA.1 appears to be due to intrinsic transmissibility. The antigenically important S1 region of spike is highly similar between BA.1 and BA.2 and we observe similar vaccine effectiveness between BA.1 and BA.2 (figure from @UKHSA https://gov.uk/government/publications/covid-19-vaccine-weekly-surveillance-repo.... 4/17
https://twitter.com/trvrb/status/1516147499890749440/photo/1

With BA.2's global dominance we expect further evolution to occur on top of BA.2. @PangoNetwork
now classifies 21 sublineages of BA.2. However, most of these sublineages are characterized by mutations thought to have little impact (figure from https://nextstrain.org/nextclade/sars-cov-2). 5/17
https://twitter.com/trvrb/status/1516147503686565889/photo/1

Here, the one to watch just based on mutations is BA.2.12.1 which has spike mutations S704L and L452Q on top of BA.2 background. Previously, L452R appeared to have an important role in promoting the spread of Delta and also showed up in Epsilon and Lambda. 6/17

The primary geographic focus for BA.2.12.1 is New York state, which was up to ~18% frequency as of April 1 from ~1% at the beginning of March. Similarly, Massachusetts has increased to 7% frequency as of April 1 from below 1% frequency at the beginning of March. 7/17
https://twitter.com/trvrb/status/1516147508820398080/photo/1

We observe a logistic growth rate of 0.06 per day in NY and 0.11 per day in MA. This is similar in magnitude to the observed advantage of BA.2 over BA.1. 8/17

We have a similar, though somewhat more complex, situation in South Africa with lineages BA.4 and BA.5 which share spike mutations L452R, F486V and reversion Q493R. Figure from @CorneliusRoemer
https://twitter.com/CorneliusRoemer/status/1514255166584893446. 9/17
https://twitter.com/trvrb/status/1516147514327527424/photo/1

It's not entirely clear to me whether BA.4 and BA.5 are sister lineages to BA.2 or sublineages of BA.2, but this distinction shouldn't matter for assessment of impact on viral circulation. 10/17

The primary geographic focus for BA.4 is Gauteng, where as of April 1 it was at ~60% frequency, and the primary focus for BA.5 is KwaZulu-Natal, where as of April 1 it was at ~55% frequency. 11/17
https://twitter.com/trvrb/status/1516147520744787970/photo/1

We observe logistic growth rates of BA.4 in Gauteng of 0.09 per day and of BA.5 in KwaZulu-Natal of 0.11 per day. Again, this is similar in magnitude to the observed advantage of BA.2 over BA.1. 12/17

Based on serological experiments it seems quite likely that 486V would confer some additional immune escape relative to BA.2 (figure from @jbloom_lab https://twitter.com/jbloom_lab/status/1513538000432472069). However, 452R/Q is not obviously a key antigenic mutation. 13/17
https://twitter.com/trvrb/status/1516147526860161025/photo/1

The hypothesis is then that 452R/Q is conferring some additional intrinsic transmission advantage. Distinguishing these scenarios is challenging however and largely relies on assessing neutralization titer in assays with 452R/Q viruses and recent human sera. 14/17

Looking forward, I expect these 452R/Q sublineages to continue to expand. As they do so, they may acquire additional mutations with the "winning" sublineage the one that accumulates the best constellation of mutations. 15/17

However, it's also possible for some other mutational constellation to arise (on top of BA.2 or otherwise) and overtake these new 452R/Q lineages. 16/17
https://twitter.com/trvrb/status/1511871614521995269/photo/1

This sort of accumulation of mutations that drive further host adaptation and antigenic drift is my general expectation for evolution in the coming months. It's possible we may have additional "Omicron-like" events, but my baseline is this steady "flu-like" scenario. 17/17

6margd
Bewerkt: apr 19, 2022, 9:12 am

>4 margd: contd.

A lot of talk about the CDC mask mandate and airplanes.

Interesting that no one is talking about what this means for those who travel on crowded buses, subways, trains that do not have any ventilation/filtration.

- Walid Gellad, MD MPHn @walidgellad | 9:08 PM · Apr 18, 2022
Professor of Medicine, U Pittsburgh. Director, Center for Pharmaceutical Policy & Prescribing
---------------------------------------------------------

This isn’t just about planes. This means a 4 year old kid with cancer who’s parents have no vehicle might be forced to sit next to a floridly sick / coughing covid patient with no mask on a bus, while going to get chemo.

But tell me about the great ventilation systems on those…

- Jerome Adams @JeromeAdamsMD | 3:14 PM · Apr 18, 2022
Father, physician, Purdue Health Equity Director. Former IN Health Commissioner and 20th US Surgeon General
----------------------------------------------------------
ETA

If airlines can ask us not to eat peanuts on board if there is someone with a peanut allergy,
why won’t they ask us to wear a mask if there’s an unvaccinated 4 year old or cancer patient on board?

- Andy Slavitt 💙💛 @ASlavitt8:23 AM · Apr 19, 2022
Former Biden White House Sr Advisor, past head of Medicare/Medicaid for Obama.

7margd
apr 19, 2022, 8:44 am

Eric Topol (Scripps) @EricTopol | 7:47 PM · Apr 18, 2022:
New and reassuring data from a prospective study of nearly 600 people immunocompromised from hematologic cancers: 3 doses of mRNA induces a strong neutralizing antibody response in most, similar to healthy controls
Image ( https://twitter.com/EricTopol/status/1516201774171901954/photo/1 )

Sabine Haggenburg et al. 2022. Three-dose mRNA-1273 vaccination schedule: sufficient antibody response in majority of immunocompromised hematology patients. MedRxiv 18 April 2022. doi: https://doi.org/10.1101/2022.04.08.22273602 https://medrxiv.org/content/10.1101/2022.04.08.22273602v1

This article is a preprint and has not been certified by peer review

Abstract
...Results In immunocompromised hematology patients, a 3rd mRNA-1273 vaccination led to median S1 IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1 IgG concentration after the 3rd vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid malignancies or multiple myeloma, and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1 IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients on or shortly after rituximab therapy, CD19-directed chimeric antigen receptor T cell therapy recipients, and chronic lymphocytic leukemia patients on ibrutinib were less or unresponsive to the 3rd vaccination. In the 27 patients who received cell therapy between the 2nd and 3rd vaccination, S1 antibodies were preserved, but a 3rd mRNA-1273 vaccination did not significantly enhance S1 IgG concentrations except for multiple myeloma patients receiving autologous HCT. A 3rd vaccination significantly improved neutralization capacity per antibody.

Conclusions and Relevance The primary schedule for immunocompromised patients with hematologic malignancies should be supplemented with a delayed 3rd vaccination. B cell lymphoma patients and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.

8margd
apr 19, 2022, 9:08 am

Mum of Cdn comedian, Brittlestar :D

Bette Reynolds @reynolds_bette | 1:06 PM · Apr 16, 2022:
IT'S STILL TOO EARLY
0:25 ( https://twitter.com/reynolds_bette/status/1515376026062401540 )

9margd
apr 19, 2022, 11:09 am

Xue Cao et al. 2022. Accelerated biological aging in COVID-19 patients. Nature Communications volume 13, Article number: 2135 (19 April 2022) https://www.nature.com/articles/s41467-022-29801-8

Abstract
Chronological age is a risk factor for SARS-CoV-2 infection and severe COVID-19...In conclusion, accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19. In addition, the accumulation of epigenetic aging from COVID-19 may contribute to the post-COVID-19 syndrome among survivors.

...Discussion
...In conclusion, our results indicate that accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19. In addition, COVID-19 could exert influence on the epigenetic clock and telomere attrition and accelerate the epigenetic aging, which may contribute to the post-COVID-19 syndrome. However, this influence is reversible in some patients. Together with other laboratory assays and clinical characteristics, it would be helpful to identify the patients with high risk of developing severe COVID-19 and post-COVID-19 syndrome.

10margd
apr 19, 2022, 5:41 pm

Older people who get covid are at increased risk of getting shingles
Linda Searing | 19 April 2022

People 50 and older who have had a mild case of covid-19 are 15 percent more likely to develop shingles (herpes zoster) within six month than are those who have not been infected by the coronavirus, according to research published in the journal Open Forum Infectious Diseases *. The risk, however, was found to be even greater for older people who were hospitalized because of a more severe covid case, making them 21 percent more likely to develop shingles than those who did not have covid. The findings stem from data on roughly 2 million people — nearly 400,000 diagnosed with covid-19 and 1.6 million who had no coronavirus infection...

https://www.washingtonpost.com/health/2022/04/19/shingles-and-covid-over-50/
-------------------------------------------------

* Amit Bhavsar et al. 2022. Increased Risk of Herpes Zoster in Adults 50 Years Old (or older) Diagnosed With COVID-19 in the United States. Open Forum Infectious Diseases, Volume 9, Issue 5, May 2022, ofac118, https://doi.org/10.1093/ofid/ofac118 https://academic.oup.com/ofid/article/9/5/ofac118/6545460

Abstract
...Results
A total of 394 677 individuals 50 years old (and older) with COVID-19 were matched with 1 577 346 individuals without COVID-19. Mean follow-up time after COVID-19 diagnosis and baseline characteristics were balanced between cohorts. Individuals diagnosed with COVID-19 had a 15% higher HZ risk than those without COVID-19 (aIRR, 1.15;...). The increased HZ risk was more pronounced (21%) following COVID-19 hospitalization (aIRR, 1.21;...).

Conclusions
We found that COVID-19 diagnosis in 50-year-olds (and older) was associated with a significantly increased risk of developing HZ, highlighting the relevance of maintaining HZ vaccination.

11margd
Bewerkt: apr 21, 2022, 9:10 am

Prof. Christina Pagel 🇺🇦 (U College London) @chrischirp | 8:24 AM · Apr 20, 2022:

Quick update on Omicron BA.4 variant - it's now about 70% of cases in Gauteng province in S Africa & cases there now climbing.

BA.4 still v low elsewhere, but other Omicron subvariants growing - e.g. B.2.12.1 in New York.

Charts by @Mike_Honey_ & @jason_u_presume
Graph-variant frequency S Africa ( https://twitter.com/chrischirp/status/1516754745402273793/photo/1 )
Image-#cases Gauteng districts ( https://twitter.com/chrischirp/status/1516754745402273793/photo/2 )

12margd
apr 21, 2022, 9:22 am

Eric Topol (Scripps) @EricTopol | 8:11 AM · Apr 21, 2022
The BA.2 wave in the United States is soon morphing to the BA2.12.1 wave, a derivative variant with even more fitness and transmission advantage

Quote Tweet
JWeiland @JPWeiland · Apr 19
New Subvariant B.2.12.1:
68% week/week advantage over BA.2
Significant growth of total numbers, doubling each week. 2.5x doubling speed compared to BA.2

New US projections model:
Graph-BA2, BA2.12.1 case projections for US ( https://twitter.com/JPWeiland/status/1516551779013513220/photo/1 )

2) Zooming in on just BA.2.12.1 (new designation please, BA.6??) we see case estimates doubling each week (CDC data) up to current. This has a more significant chance to break through the shift in seasons to create a real wave than BA.2 could muster.
https://twitter.com/JPWeiland/status/1516552823890227214/photo/1

13margd
apr 22, 2022, 6:51 am

A puzzling phenomenon: Patients report a rebound of COVID-19 symptoms after taking the antiviral Paxlovid
Kay Lazar | Updated April 21, 2022

...Pfizer noted in the documents submitted last fall to federal regulators for its emergency use authorization that “several subjects appeared to have a rebound in SARS-CoV-2 RNA levels around Day 10 or Day 14” but said that “currently there are no clear signals” the virus had developed a resistance to one of Paxlovid’s primary components. The documents said Pfizer would continue analyzing the data.

In a statement to the Globe, the company said, “We continue to monitor data from our ongoing clinical studies and real-world evidence. We have not seen any resistance to Paxlovid, and remain very confident in its clinical effectiveness.”

Dr. Michael Charness, chief of staff at the VA Boston Healthcare System, recently completed an in-depth study of one patient who experienced a rebound after taking Paxlovid.

Charness sequenced three nasal swabs from the patient and tested the patient for a battery of other respiratory illnesses. He concluded that the virus was not resistant to Paxlovid and that the patient had not been infected with any other respiratory viruses or other variants of COVID. Rather, he concluded some patients may need a longer course of treatment for their immune system to mount a robust defense....

https://www.bostonglobe.com/2022/04/21/metro/puzzling-phenomenon-patients-report...

14margd
apr 22, 2022, 8:56 am

Today we sent a letter to FDA with 60+ signatories advocating for FDA guidance in assessing T cell responses in COVID vaccine studies. T cell immunity is likely a major player in protection from disease. We should analyze T cells (with Abs and memory B cells) across studies.
Letter excerpt ( https://twitter.com/EJohnWherry/status/1517123070531497984/photo/1 )

- E. John Wherry (U PA) @EJohnWherry | 8:48 AM · Apr 21, 2022

15margd
apr 22, 2022, 9:22 am

Covid Drugs Save Lives, but Americans Can’t Get Them
Zeynep Tufekci | April 22, 2022

...Paxlovid, an antiviral treatment developed by Pfizer, an American pharmaceutical company, is highly effective for reducing hospitalizations and deaths in high-risk patients, as long as it is started early. This is especially important for elderly or immunocompromised people, since their immune systems are not as robust as others’ against viruses, even when vaccinated. In his State of the Union address, Biden announced a Test to Treat initiative to provide such pills on the spot in pharmacies when someone tests positive.

...A similar situation is underway for Evusheld, a Covid drug approved in December for the millions of immunocompromised people, like transplant patients and those on medications that can suppress the immune system for conditions like rheumatoid arthritis. In trials, the drug reduced symptomatic infections by about 83 percent at six months. This drug provides them with extra protection for six months as a prophylactic. It’s been approved for months, and Biden also mentioned treatments for the immunocompromised in his State of the Union address. The federal government bought 1,700,000 doses, to be distributed free.

...There’s more the federal government can do now, like start a robust physician and patient outreach program and work to clarify and balance the supply of therapeutics for Covid so that millions of immunocompromised people can better protect themselves and high-risk people who get infected can avoid severe disease.

However, states should be aware that this may not be coming and should begin their own programs and maybe even cooperate to build shared infrastructure...

https://www.nytimes.com/2022/04/22/opinion/covid-pandemic-drugs-treatment.html

16margd
Bewerkt: apr 22, 2022, 1:41 pm

Tracy Høeg, MD, PhD @TracyBethHoeg | 9:09 PM · Apr 21, 2022:
MD w/PhD in Epi & Public Health. 🇩🇰 🇺🇸 citizen. Mom of 4. PM&R Sports & Interventional Spine @ NCOA, Research Associate @ucdavis, Epidemiologist @HealthyFla (FL Dept of Health)
🧵 https://twitter.com/TracyBethHoeg/status/1517309675015876608

Massive Nordic study finds risk of post-vaccination myo/pericarditis resulting in hospitalization in males 16-24 of 380/million (1/2600) post pfizer-moderna combination
This is 28x higher than the 13.7/million rate they found post-covid

Myocarditis rates lower in males 16-24 with pfizer alone:
22/million post pfizer dose 1
53/million post pfizer dose 2
29/million post moderna dose 1
138/million post moderna dose 2
All higher than 13.7/million post covid
above are myo(not peri)carditis& hospitalized cases only

220-360/million myopericarditis among boys 12-17 post dose 2 pfizer and
and 65-150/million myopericarditis in men 18-29
(but post covid myo rate based on too low a denominator in this study; not reliable)
https://cdc.gov/mmwr/volumes/7

I hope the Nordic data (& UK data I discussed below) will put to rest the idea that post covid myocarditis is ALWAYS more common than post vax myo in every demographic.
In males 16-24, Nordic data suggest any dose mRNA vax myo is higher post vax

JoHo @JHowardBrainMD | 11:55 AM · Apr 22, 2022
So basically, the Pfizer vaccine, which all kids will get in USA, has a 1 in 19,000 risk of vaccine myocarditis after the second dose. Almost all kids recover after a short time.
But that’s not how you chose to frame it.
Why?

rv @670rv | 12:12 PM · Apr 22, 2022:
Will she care to comment about this:
Transient something against permanent organ damage.
Persisting pulmonary dysfunction in pediatric post-acute Covid-19:
https://medrxiv.org/content/10.1101/2022.02.21.22270909v1.full.pdf
----------------------------------------------------------

Øystein Karlstad et al. 2022. SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents.
JAMA Cardiol. Published online April 20, 2022. doi:10.1001/jamacardio.2022.0583 https://jamanetwork.com/journals/jamacardiology/fullarticle/2791253

Key Points
Question Is SARS-CoV-2 messenger RNA (mRNA) vaccination associated with risk of myocarditis?

Findings In a cohort study of 23.1 million residents across 4 Nordic countries, risk of myocarditis after the first and second doses of SARS-CoV-2 mRNA vaccines was highest in young males aged 16 to 24 years after the second dose. For young males receiving 2 doses of the same vaccine, data were compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after second-dose BNT162b2, and between 9 and 28 per 100 000 vaccinees after second-dose mRNA-1273.

Meaning The risk of myocarditis in this large cohort study was highest in young males after the second SARS-CoV-2 vaccine dose, and this risk should be balanced against the benefits of protecting against severe COVID-19 disease.
------------------------------------------------------------

Ann Marie Navar and Robert O. Bonow. 2022. Communicating the Benefits of Vaccination in Light of Potential Risks (Editor's Note). JAMA Cardiol. Published online April 20, 2022. doi:10.1001/jamacardio.2022.0590 https://jamanetwork.com/journals/jamacardiology/article-abstract/2791257

------------------------------------------------------------

Limor Friedensohn et al.2022. Myocarditis Following a Third BNT162b2 (Pfizer) Vaccination Dose in Military Recruits in Israel (Research Letter). JAMA. Published online March 17, 2022. doi:10.1001/jama.2022.4425 https://jamanetwork.com/journals/jama/fullarticle/2790421

...Discussion
This study found a low risk of myocarditis after a third dose of BNT162b2 in Israeli military recruits. The incidence was lower than observed a week after a second dose of the vaccine in a similar Israeli military population (5.07 per 100 000 vaccines)... However, the myocarditis incidence for 18- to 24-year-old men was higher than observed for a US male population (5.243 per 100 000 vaccines)... The incidence of myocarditis following the second dose of the vaccine varies according to follow-up times in studies... and the definition of myocarditis used. Therefore, comparisons should be made with caution.

...The cause of the lower incidence of myocarditis following a third dose in comparison with the incidence after the second dose requires future research.

17margd
apr 25, 2022, 9:57 am

Colleen Griffith (chem engineer) @Griffith17431 · Apr 23
https://twitter.com/Griffith17431/status/1517948334970966016

SARS-CoV-2 infection increases your risk of fungal infection 🤢
“These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that” 1/3

“impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies”2/3

“to prevent and treat fungal superinfections in COVID-19 patients.”
3/3
-------------------------------------------------------

Beeke Tappe et al. 2022. COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds. MedRxiv 22 April 2022.
doi: https://doi.org/10.1101/2022.04.21.22274082 https://www.medrxiv.org/content/10.1101/2022.04.21.22274082v1

This article is a preprint and has not been certified by peer review

Abstract
Patients suffering from coronavirus disease-2019 (COVID-19) are at high risk for deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM). Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood (WB) stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, WB from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.

...Discussion
...this study provides an inaugural characterization of impaired immune responses to A. fumigatus and R. arrhizus antigens in patients with and after COVID-19 pneumonia, beyond the well-studied adverse impact of GCS. The predicted immune pathways will serve as a hypothesis-generating foundation for detailed follow-up studies of the immune predisposition to secondary mold infections after respiratory viral infections, including COVID-19, influenza, as well as infections due to respiratory syncytial virus, parainfluenza, and adenovirus. If further validated in multi-center studies and/or suitable animal models, the identified pathways can open new avenues for immunotherapeutic strategies to prevent and treat fungal superinfections in patients with post-viral immune impairment.

18margd
Bewerkt: apr 26, 2022, 8:10 am

I recall reading earlier that Puerto Rico was doing better than the 50 states in vaccination rates?
BA.2...

Eric Topol @EricTopol | 10:53 AM · Apr 23, 2022:
The hardest hit region for the US BA.2 wave so far isn't the Northeast. It's Puerto Rico
GRAPHS
https://twitter.com/EricTopol/status/1517879220751327235/photo/1
https://twitter.com/EricTopol/status/1517879220751327235/photo/2
https://twitter.com/EricTopol/status/1517879220751327235/photo/3
https://twitter.com/EricTopol/status/1517879220751327235/photo/4

Eric Topol @EricTopol | 10:08 AM · Apr 25, 2022:
The situation in Puerto Rico is getting worse, now a new case rate 88/100,000, twice as high as any US state, and hospitalizations are in steep ascent
https://nytimes.com/interactive/2021/us/puerto-rico-covid-cases.html
Graphs https://twitter.com/EricTopol/status/1518592709660868608/photo/1

19margd
Bewerkt: apr 26, 2022, 10:09 am

Pre-omicron, "Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss ..., but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes."

Maxime Taquet @MaximeTaquet | 8:55 AM · Apr 22, 2022:
NIHR @OxHealthBRC Senior Research Fellow, ACF @UniofOxford & @OxfordHealthNHS, Researcher at @harvardmed . Interested in digital psychiatry, brain imaging, EHR

Our findings on outcomes of breakthrough #COVID19 infections are out in @BrainBehavImm.* We show obvious protective effect of vaccines on acute severe outcomes (e.g. ICU admission) but also the lack of obvious protection against #LongCovid w/ @qdercon @OxPsychiatry @OxHealthBRC

* MaximeTaquet et al. 2022. Six-month sequelae of post-vaccination SARS-CoV-2 infection: A retrospective cohort study of 10,024 breakthrough infections. Brain, Behavior, and Immunity
Volume 103, July 2022, Pages 154-162. https://doi.org/10.1016/j.bbi.2022.04.013

Text-abstract ( https://twitter.com/MaximeTaquet/status/1517487304436236290/photo/1 )
------------------------------------------------

Pre-omicron complications which respond and don't to vaccination, 1 &2 doses, under/over 60:
https://twitter.com/KunstJonas/status/1517394410719399937/photo/1

20Molly3028
Bewerkt: apr 26, 2022, 9:01 am

https://www.mediaite.com/opinion/jon-karl-hails-fox-news-pandemic-coverage-as-ve...
Jon Karl Hails Fox News Pandemic Coverage as ‘Very Responsible’, Despite Tucker Carlson, Alex Berenson, Etc.

***
But Tucker, the ratings juggernaut at the end of each day, canceled out all of the responsible reporting that MAY have taken place on the network throughout the day.

21margd
apr 26, 2022, 12:09 pm

Eric Topol (Scripps) @EricTopol | 3:47 PM · Apr 22, 2022:
"These findings suggest an unexpected alternative mechanism for #LongCovid. Rather than persistent immune activation, we observed abnormal immune downmodulation, which is normalized by leronlimab (a CCR5 antibody)"
-------------------------------------------------------

Norman B Gaylis et al. 2022. Reduced Cell Surface Levels of C-C Chemokine Receptor 5* and Immunosuppression in Long Coronavirus Disease 2019 Syndrome (Corrected Proof). Clinical Infectious Diseases, ciac226. Published: 22 April 2022. https://doi.org/10.1093/cid/ciac226 https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciac226/65...

Abstract
In an exploratory trial treating “long COVID” with the CCR5*-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab.
Clinical Trials Registration. NCT04678830.

Figure 1 ( https://twitter.com/EricTopol/status/1517590910279700480/photo/1 )

* CCR5 Protein--C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. In humans, the CCR5 gene that encodes the CCR5 protein is located on the short arm at position 21 on chromosome 3. (Wikipedia)

*CCR5 (C-C Motif Chemokine Receptor 5) is a Protein Coding gene. Diseases associated with CCR5 include West Nile Virus and Type 1 Diabetes Mellitus 22. Among its related pathways are Cytokine Signaling in Immune system and CCR5 Pathway in Macrophages. Feb 21, 2022 ( https://www.genecards.org/cgi-bin/carddisp.pl?gene=CCR5 )

22margd
apr 27, 2022, 3:17 pm

>18 margd: contd.

Eric Topol @EricTopol | 10:47 AM · Apr 27, 2022
Why is Puerto Rico at 100 new cases/100K residents, by far the highest for the US, but New York, with dominant B.2.12.1 (and its L452Q mutation), at 33/100K?

Likely contributor:
Seroprevalence Puerto Rico 37% vs NY 62% at end February 2022

Graph-confirmed cases NY & PR, Mar 2020-Apr 2022
https://twitter.com/EricTopol/status/1519327342019026944/photo/1

Nationwide COVID-19 Infection-Induced Antibody Seroprevalence (Commercial laboratories)
https://covid.cdc.gov/covid-data-tracker/#national-lab

23margd
apr 27, 2022, 3:45 pm

Eric Topol @EricTopol | 11:14 AM · Apr 27, 2022
🆕 @NatureMicrobiol
Good to see another #SARSCoV2 main protease (mPro) pill, like Paxlovid, that blocks replication for all variants including Omicron

Bao-Xue Quan et al. 2022. An orally available Mpro inhibitor is effective against wild-type SARS-CoV-2 and variants including Omicron. Nature Microbiology (27 April 2022) https://www.nature.com/articles/s41564-022-01119-7

Abstract
...The main protease (Mpro) of SARS-CoV-2 is an attractive drug target (for an antiviral) because of its central role in viral replication and its conservation among variants. We herein report a series of potent α-ketoamide-containing Mpro inhibitors obtained using the Ugi four-component reaction. The prioritized compound, Y180, showed an IC50* of 8.1 nM against SARS-CoV-2 Mpro and had oral bioavailability of 92.9%, 31.9% and 85.7% in mice, rats and dogs, respectively. Y180 protected against wild-type SARS-CoV-2, B.1.1.7 (Alpha), B.1.617.1 (Kappa) and P.3 (Theta), with EC50 of 11.4, 20.3, 34.4 and 23.7 nM, respectively. Oral treatment with Y180 displayed a remarkable antiviral potency and substantially ameliorated the virus-induced tissue damage in both nasal turbinate and lung of B.1.1.7-infected K18-human ACE2 (K18-hACE2) transgenic mice. Therapeutic treatment with Y180 improved the survival of mice from 0 to 44.4% ... upon B.1.617.1 infection in the lethal infection model. Importantly, Y180 was also highly effective against the B.1.1.529 (Omicron) variant both in vitro and in vivo. Overall, our study provides a promising lead compound for oral drug development against SARS-CoV-2.

* IC50 is a quantitative measure that indicates how much of a particular inhibitory substance (e.g. drug) is needed to inhibit, in vitro, a given biological process or biological component by 50%. The biological component could be an enzyme, cell, cell receptor or microorganism. (Wikipedia)

24margd
apr 28, 2022, 7:32 am

Googled antihistamine / antacid famotidine and found it's still being studied as a therapeutic, giving encouraging results in a phase 2 trial: "Rate of symptom resolution was improved for patients taking famotidine (highly significant). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days ... for famotidine and 11.4 days ... for placebo treated patients... In the absence of strong alternatives, famotidine might be considered as a treatment for symptomatic outpatients with COVID-19."

Dosage effective in study was 80 mg 3X daily; OTC pills are 10 or 20 mg, and while relatively safe, there are some contraindications so one would want to speak to MD.

Christina M Brennan et al. 2022. Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial. BMJ Gut Volume 71, Issue 5 pp 879–888. doi:10.1136/gutjnl-2022-326952 https://gut.bmj.com/content/gutjnl/71/5/879.full.pdf

Abstract
Objective We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19.

Design Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory).

Results Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p

25margd
apr 28, 2022, 8:45 am

#24 in thread 26, 10 Dec 2022. mouthwashes, contd.

Quickly googled to see progress, if any, studying effectiveness of mouthwash against SARS-CoV-19. Six months ago, dental assistant offered me a swish of something (hydrogen peroxide?), which she said was recommended by CDC for use in their practices in these COVID times. The two studies below come via NATURE, which is a highly regarded science journal. Looks like these mouthwashes are effective against the virus
cetylperidinium chloride (Colgate Plax® Fruity Fresh),
chlorhexidine (Oradex)
hexetidine (Bactidol®)
povidone iodine / PVP-I (BETADINE gargle and mouthwash)
----------------------------------------------------------------------

Vunjia Tiong et al. 2021. The effectiveness of various gargle formulations and salt water against SARS-CoV-2. (Nature) Scientific Reports volume 11, Article number: 20502 (2021) https://doi.org/10.1038/s41598-021-99866-w https://www.nature.com/articles/s41598-021-99866-w.pdf

Abstract
The COVID-19 is difficult to contain due to its high transmissibility rate and a long incubation period of 5 to 14 days. Moreover, more than half of the infected patients were young and asymptomatic. Virus transmission through asymptomatic patients is a major challenge to disease containment. Due to limited treatment options, preventive measures play major role in controlling the disease spread. Gargling with antiseptic formulation may have potential role in eliminating the virus in the throat. Four commercially available mouthwash/gargle formulations were tested for virucidal activity against SARS-CoV-2 in both clean (0.3 g/l BSA) and dirty (0.3 g/l BSA + 3 mL/L human erythrocytes) conditions at time points 30 and 60 s. The virus was isolated and propagated in Vero E6 cells. The cytotoxicity of the products to the Vero E6 was evaluated by kill time assay based on the European Standard EN14476:2013/FprA1:2015 protocol. Virus titres were calculated as 50% tissue culture infectious dose (TCID50/mL) using the Spearman-Karber method. A reduction in virus titer of 4 log10 corresponds to an inactivation of ≥ 99.99%. Formulations with cetylperidinium chloride, chlorhexidine and hexitidine achieved > 4 log10 reduction in viral titres when exposed within 30 s under both clean and dirty conditions. Thymol formulations achieved only 0.5 log10 reduction in viral titres. In addition, salt water was not proven effective. Gargle formulations with cetylperidinium chloride (Colgate Plax® Fruity Fresh), chlorhexidine (Oradex) and hexetidine (Bactidol®) have great potential in reducing SAR-CoV-2 at the source of entry into the body, thus minimizing risk of transmission of COVID-19.

...Conclusions
A number of commercially available mouthwash/gargle formulations containing cetylperidinium chloride and hexetidine demonstrated potent and rapid virucidal activity of ≥ 5 log10 reduction of SARS-CoV-2 at 30 s. Chlorhexidine digluconate was slightly less effective,while salt water and thymol did not show any significant reduction in virus titre. This information gives more options for healthcare workers particularly dentists, anaesthetists, maxillofacial surgeons and otorhinolaryngologists to routinely practice pre-procedural gargling with readily available formulations. The practice of using tested mouthwash/gargle products should also be extended to high-risk groups and the general population to minimize the risk of viral transmission particularly from asymptomatic/presymptomatic carriers.
________________________________________________________

Pouya Hassandarvish et al. 2020. In vitro virucidal activity of povidone iodine gargle and mouthwash against SARS-CoV-2: implications for dental practice. Br Dent J. 2020 Dec 10 : 1–4.
doi: 10.1038/s41415-020-2402-0 https://www.nature.com/articles/s41415-020-2402-0

Abstract

Introduction Virus particles in respiratory droplets and aerosols generated during medical/dental procedures are a potential source of SARS-CoV-2 cross infection. In the dental setting, oral decontamination could be an important adjunct to personal protective equipment and is recommended by a number of national COVID-19 guidance documents for dental settings.

Aim To assess the in vitrovirucidal activity of an oral povidone iodine (PVP-I) product against SARS-CoV-2.

Material and methods BETADINE gargle and mouthwash (1% PVP-I) was tested against SARS-CoV-2 virus under both clean and dirty conditions using a suspension assay based on EN14476 methodology. Virucidal activity of the product, undiluted and at 1:2 dilution, was tested at contact times of 15, 30 and 60 seconds. Viral titres were calculated using the Spearman-Kärber method and reported as median tissue culture infectious dose (TCID50/ml).

Results The undiluted product achieved >5 margd: log10 reduction in viral titres compared to the control at 15, 30 and 60 seconds under both clean and dirty conditions. At a twofold dilution (0.5% PVP-I), the test product demonstrated >4 margd: log10 kill at 15 seconds and >5 margd: log10 kill at 30 and 60 seconds in both clean and dirty conditions.

Conclusion PVP-I gargle and mouthwash product, undiluted and at 1:2 dilution, demonstrated potent and rapid virucidal activity (≥4 log10 reduction of viral titre) in 15 seconds against SARS-CoV-2 in vitro. The PVP-I gargle and mouthwash product is widely available and could be readily integrated into infection control measures during dental treatment including pre-procedural oral decontamination.

...Key points
Close contact and potential for aerosol generation increase risk of SARS-CoV-2 exposure during medical and dental procedures.
Pre-procedural mouth rinses are recommended as an additional measure to reduce cross-infection risk in dental settings.
PVP-I (1%) gargle and mouthwash showed 99.99% kill rate of SARS-CoV-2 in vitro within 15 seconds of contact in clean and dirty conditions.
The use of PVP-I-containing pre-procedural mouth rinse to reduce oral viral load could be recommended in addition to other protective measures.

...Conclusion
Dental practice poses a potential risk of COVID-19 cross infection among patients and dental health professionals. In our study, we present direct evidence of potent virucidal activity of PVP-I gargle/mouthwash against SARS-CoV-2 in just 15 seconds in vitro. Specifically, it can potentially be used as a pre-procedural mouthwash as recommended by national dental guidelines. In today's scenario, PVP-I gargle/mouthwash may be an adjunct to PPE to help reduce the risk of COVID-19 cross infection in dental practices.

26margd
apr 28, 2022, 10:44 am

David Fisman (epidemiology, U Toronto) @DFisman | 1:13 AM · Apr 28, 2022:
https://twitter.com/DFisman/status/1519545406778134531
This is really interesting. I was unaware of the post-delta pediatric hepatitis surge in India…the timing relative to MIS-C would suggest a post-infectious phenomenon

Quote Tweet
Chris Turnbull (journalist) @EnemyInAState | 12:03 PM · Apr 14, 2022:
25-tweet thread ( https://twitter.com/EnemyInAState/status/1514635580486860804 )
1/ Covid: Study from India shows 'sudden rise' in children with Hepatitis after 'mild' and asymptomatic infections as UKHSA claims that the sudden rise in Hep in kids in the UK is due to a common cold virus. Kids developed Hep after mild and asymptomatic infections.

Graph-incidence hepatitis & MIS-C, India, Apr-June 2021
https://twitter.com/EnemyInAState/status/1514635580486860804/photo/1

2/ The 'sudden rise' has been reported in the UK of late:
Gov UK news story ( https://twitter.com/EnemyInAState/status/1512488753264492544/photo/1 )

3/ Another study here that demonstrates that Sars 2 causes liver damage in kids and caused a surge of Hep in India during their second wave (Delta).
https://twitter.com/EnemyInAState/status/1514636830062399506/photo/1

4/ The Authors write:
'We observed a sudden rise of features of hepatitis in a group of pediatric patients during the second wave of SARS CoV-2 infections, where “children or adolescents developing sudden onset acute hepatitis with no history of pre-existing...

...25/ +

27margd
apr 29, 2022, 6:30 am

"unvaccinated people contribut(ed) to infections among those who were vaccinated at a rate higher than would have been expected based on contact numbers alone"

David Fisman (epidemiologist, U Toronto) @DFisman | 11:42 AM · Apr 28, 2022:
It’s been an interesting couple of years, but I’ve NEVER experienced the vitriol I’ve received over the past 3 days for stating that simple fact.

David N. Fisman et al. 2022. Impact of population mixing between vaccinated and unvaccinated subpopulations on infectious disease dynamics: implications for SARS-CoV-2 transmission. CMAJ April 25, 2022 194 (16) E573-E580; DOI: https://doi.org/10.1503/cmaj.212105 https://www.cmaj.ca/content/194/16/E573

Abstract
...Results: We found that the risk of infection was markedly higher among unvaccinated people than among vaccinated people under all mixing assumptions. The contact-adjusted contribution of unvaccinated people to infection risk was disproportionate, with unvaccinated people contributing to infections among those who were vaccinated at a rate higher than would have been expected based on contact numbers alone. We found that as like-with-like mixing increased, attack rates among vaccinated people decreased from 15% to 10% (and increased from 62% to 79% among unvaccinated people), but the contact-adjusted contribution to risk among vaccinated people derived from contact with unvaccinated people increased.

Interpretation: Although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to people who are unvaccinated, their choices affect risk of viral infection among those who are vaccinated in a manner that is disproportionate to the portion of unvaccinated people in the population.

...Conclusion
Using simple mathematical modelling, we have shown that, although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to those who are unvaccinated, the choice of some individuals to refuse vaccination is likely to affect the health and safety of vaccinated people in a manner disproportionate to the fraction of unvaccinated people in the population. Risk among unvaccinated people cannot be considered self-regarding, and considerations around equity and justice for people who do choose to be vaccinated, as well as those who choose not to be, need to be considered in the formulation of vaccination policy. It is unlikely that SARS-CoV-2 will be eliminated, and our findings will likely be relevant to future seasonal SARS-CoV-2 epidemics or in the face of emerging variants.

28margd
apr 30, 2022, 8:20 am

Can We Eradicate COVID-19? (4:21)
Dr. Fauci: ‘Are we going to eradicate COVID-19? I say that’s almost impossible.’
Now This News | 6:33 PM · Apr 29, 2022
https://twitter.com/nowthisnews/status/1520169304712527876

29margd
mei 2, 2022, 6:58 am

U of Toronto assoc prof:
Omicron is not mild, young people are not invincible, govt data is not necessarily reliable.

Tara Moriarty (U of TORONTO) @MoriartyLab | 8:44 PM · Apr 30, 2022:
https://twitter.com/MoriartyLab/status/1520564666216468480

38% of all of Canada's reported COVID hospitalizations to date have been in the last 4 months
28% of reported ICU admissions of the entire epidemic in the last 4 months (with more coming from current wave)
23% of total reported epidemic deaths, with more coming from this wave.

Among people 19 and younger,
64% of total epidemic hospitalizations have occurred during the Omicron wave.
55% of ICU admissions
49% of deaths

Among people 20-39,
38% of total epidemic hospitalizations have occurred during the Omicron wave.
24% of ICU admissions
20% of deaths

Among people 40-59,
27% of total epidemic hospitalizations have occurred during the Omicron wave.
24% of ICU admissions
23% of deaths

Among people 60-79,
37% of total epidemic hospitalizations have occurred during the Omicron wave.
29% of ICU admissions
25% of deaths

Among people 80 and older,
44% of total epidemic hospitalizations have occurred during the Omicron wave.
36% of ICU admissions
21% of deaths

...for the "with" vs "of" crowd, here's how many "with" COVID deaths are likely missing from reported data in each province:
CAN 5,734
AB 504
BC 874
MB 174
NB 296
NL 53
NS 103
ON 3,710
PEI 9
SK 29
The provinces with biggest reporting problems currently are BC, NB, ON...

30margd
mei 2, 2022, 3:21 pm

Bin Wang et al. 2022. Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions (Review). (NATURE) Signal Transduction and Targeted Therapy volume 7, Article number: 143 (29 April 2022) https://www.nature.com/articles/s41392-022-00986-0

Abstract
...In the present review, we explore the associations between host microbiota and COVID-19 in terms of their clinical relevance. Microbiota-derived metabolites or components are the main mediators of microbiota-host interactions that influence host immunity. Hence, we discuss the potential mechanisms by which microbiota-derived metabolites or components modulate the host immune responses to SARS-CoV-2 infection. Finally, we review and discuss a variety of possible microbiota-based prophylaxes and therapies for COVID-19 and PACS, including fecal microbiota transplantation (FMT), probiotics, prebiotics, microbiota-derived metabolites, and engineered symbiotic bacteria. This treatment strategy could modulate host microbiota and mitigate virus-induced inflammation.

...CONCLUSIONS AND PERSPECTIVES
...Certain studies proposed that the omicron variant can evade infection- and vaccination-induced antibodies and exacerbate existing public health risks... In contrast, other studies demonstrated comparatively lower hospitalization rates associated with the omicron variant than the wild type SARS-CoV-2... However, the differences among the omicron and wild type strains in terms of their relative impact on host microbiota alterations are unknown. Future investigations might help develop
microbiota-based therapeutics customized for omicron variant infections.

Not only various intrinsic host factors (such as age, sex, genetics, and comorbidities), but also extrinsic factors (such as rural versus urban location, geographical location, season, and toxins) have been shown to influence the composition of the microbiota... Moreover,microbiota composition varies widely among individuals and populations... They also greatly differ in terms of their SARS-CoV-
2 symptoms. Cases may range from asymptomatic to acute pneumonia... However, there is little data available on the associations among microbiota composition and coronavirus susceptibility. Thus, clarification of the relationships between SARS-CoV-2 susceptibility and microbiota composition may facilitate the design and deployment of prophylactic and therapeutic measures against the new SARS-CoV-2 strains. It is clear that microbiota are strongly implicated in host immune responses to various diseases including COVID-19. Nevertheless, it remains to be determined whether microbiota-based therapeutics influence COVID-19 outcome. This research focus should be prioritized as the COVID-19
pandemic continues to be severe in certain parts of the world.

31margd
mei 4, 2022, 8:50 am

Joey Fox, P. Eng, M.A.Sc @joeyfox85 | 8:23 PM · May 3, 2022
HVAC Engineer. Building Automation Systems. #COVIDisAirborne . Ventilation, Filtration, UVGI. If you know how it spreads, you know how to stop it.

How Long to Flush a Space?

You have a bunch of people working in your house. You are super cautious and don't want to take any chances, so you put on your N95, HEPA filters and open windows while they are there. Once they leave, how long do you have to continue this for?

Step 1 - determine how many air changes you need. ASHRAE recommends 3 air changes = 95% reduction in virus particles. If you're more cautious, then go for 5 air changes = 99.3% reduction in virus particles. You can do more, but the benefit is minimal.
https://ashrae.org/technical-resources/reopening-of-schools-and-universities
text excerpt ( https://twitter.com/joeyfox85/status/1521646643065626624/photo/1 )

Step 2 - determine the volume of the place you want to flush. Houses usually have 8' ceilings. You can measure it out.

Step 3 - determine the clean air delivery rate (CADR). For a CR (Corsi Reosenthal) box on low, it's 275 CFM. Blast it on high and you'll get 425 CFM.

For other HEPA filters, get the CADR online or if you have a rated sq ft for it, divide that by 1.55 to get the CADR. For bathroom exhaust fans, assume 1 CFM/sq ft. With 8' ceilings, it's 8 min/ air change.

Windows are tough to calculate:
https://twitter.com/DavidElfstrom/status/1340665816992403458?s=20&t=M9zavzql...

If you open up windows and doors + fans, it could be 1 air change (AC) every few minutes. If you are flushing, using fans (even without filters) around the house helps to mix the air better.

Step 4 - calculate: AC= CADR x time / volume
or
Time (min) = 5 AC x volume/CADR

One more thing you can do - if you have a CO2 sensor, make sure it's calibrated, open up the windows and leave the room. When the CO2 is very close to outdoor air levels, wait a bit and you're good to go.

32margd
Bewerkt: mei 4, 2022, 10:16 am

Another rare virus puzzle: They got sick, got treated, got covid again
Carolyn Y. Johnson | April 27, 2022

...Infectious-disease experts agree that this phenomenon of the virus rebounding after some patients take the drug (Paxlovid) appears to be real but rare. Exactly how often it occurs, why it happens and what — if anything — to do about it remain matters of debate.

What’s clear is that patients should be warned it is possible so they don’t panic — and so that they know to test again if they start feeling ill. More data is needed to understand what is going on. Paxlovid, made by the drug giant Pfizer, remains a useful drug, even though it has sparked a new mystery.

...One of the top worries accompanying antiviral drugs is the threat of resistance, when the virus evolves to evade the treatment...no evidence

...it raises the concern that some people — whether they have taken the drug or not — could be infectious long after they think they are in the clear, and after guidelines suggest they can stop taking precautions.

...If such cases turn out to be exceedingly rare, then these case reports may be a sporadic curiosity — something to warn patients could happen. If more common, it could lead to tweaks in treatment regimens...

https://www.washingtonpost.com/health/2022/04/27/paxlovid-second-case-covid/
-----------------------------------------------------

Excerpt from USFDA analyisi of Pfizer data on Paxlovid:
https://twitter.com/DrEricDing/status/1521723944851714048/photo/1

33margd
mei 4, 2022, 10:24 am

Nose Spray Vaccines Could Quash COVID Virus Variants
Three nasal spritzes, now in advanced trials, could trigger stronger immunity than shots in the arm
Marla Broadfoot | May 3, 2022

...To block infections entirely, scientists want to deliver inoculations to the site where the virus first makes contact: the nose. People could simply spray the vaccines up their nostrils at home, making the preparation much easier to administer. There are eight of these nasal vaccines in clinical development now and three in phase 3 clinical trials, where they are being tested in large groups of people. But making these vaccines has proven to be slow going because of the challenges of creating formulations for this unfamiliar route that are both safe and effective.

What could be most important about nasal vaccines is their ability to awaken a powerful bodily defender known as mucosal immunity, something largely untapped by the standard shots. The mucosal system relies on specialized cells and antibodies within the mucus-rich lining of the nose and other parts of our airways, as well as the gut. These elements move fast and arrive first, stopping the virus, SARS-CoV-2, before it can create a deep infection. “We are dealing with a different threat than we were in 2020,” says Akiko Iwasaki, an immunologist at Yale University. “If we want to contain the spread of the virus, the only way to do that is through mucosal immunity.”

...The more familiar shots in the arm create a type of immune response known as systemic immunity, which produces what are called immunoglobulin G (IgG) antibodies. They circulate throughout the bloodstream and patrol for the virus. Nasal sprays assemble a separate set of antibodies known as immunoglobulin A (IgA). These populate the spongy mucosal tissues of the nose, mouth and throat, where the COVID-causing coronavirus first lands...

https://www.scientificamerican.com/article/nose-spray-vaccines-could-quash-covid...

34margd
mei 4, 2022, 2:56 pm

With usual suspects ruled out, disease detectives try to crack mystery of viral hepatitis cases in kids
Helen Branswell | May 4, 2022

...Though the finding of adenovirus type 41 (Scotland, Alabama) is enticing and seems, as (Markus Buchfellner, a pediatric infectious diseases specialist at Children’s of Alabama) put it, too consistent to be by chance, investigators know they can’t stop searching. Getting too invested in an idea about the possible cause of an outbreak is a rookie mistake. You have to remain open to what the evidence reveals, said (Julia Petras, an EIS (Epidemic Intelligence Service) officer at the CDC).

...Many armchair epidemiologists on Twitter feel Covid infection — current or previous — could explain the hepatitis and seem to feel the idea has gotten short shrift, though that is still very much on the list of working hypotheses listed in the UKHSA report.

...Still another theory is that the public health measures employed over the past couple of years to reduce spread of Covid-19 may have set up some children to have more severe illness when they contracted a bug that might previously have been innocuous. Masking, online schooling, and social distancing have dramatically reduced transmission of viruses that cause colds or influenza.

...Why is adenovirus 41 causing hepatitis when it really hasn’t before?

https://www.statnews.com/2022/05/04/with-usual-suspects-ruled-out-disease-detect...

35margd
mei 5, 2022, 12:17 pm

Israeli researchers warn of new international COVID wave, driven by Delta comeback
Nathan Jeffay | 4 May 2022

Omicron didn’t wipe out the previous variant, which is super-resilient and could reemerge with a vengeance, according to peer-reviewed study based on cutting-edge sewage monitoring...

https://www.timesofisrael.com/israeli-researchers-warn-of-new-international-covi...

----------------------------------------------------------------

KarinYaniva et al. 2022. Managing an evolving pandemic: Cryptic circulation of the Delta variant during the Omicron rise. Science of The Total Environment. Available online 30 April 2022. https://doi.org/10.1016/j.scitotenv.2022.155599 https://www.sciencedirect.com/science/article/pii/S004896972202695X?via%3Dihub

Journal pre-proof

Highlights
• Wastewater-based epidemiology is recommended tool for pandemic containment.
• Development of sensitive RT-qPCR assay for the direct detection of Omicron variant
• Wastewater detection illustrating circulation of Delta variant in parallel to Omicron rise.
• Developed SIR model suggest decrease in Omicron levels while Delta will maintain its circulation.

Abstract
... it can be expected that the Omicron levels will decrease until eliminated, while Delta variant will maintain its cryptic circulation. If this comes to pass, the mentioned cryptic circulation may result in the reemergence of a Delta morbidity wave or in the possible generation of a new threatening variant. In conclusion, the deployment of wastewater-based epidemiology is recommended as a convenient and representative tool for pandemic containment.

36margd
mei 8, 2022, 1:34 pm

Cognitive Impairment From Severe COVID-19 Equivalent to 20 Years of Aging – Losing 10 IQ Points
University of Cambridge | May 8, 2022

...Cognitive impairment as a result of severe COVID-19 is similar to that sustained between 50 and 70 years of age and is the equivalent to losing 10 IQ points, say a team of scientists from the University of Cambridge and Imperial College London.

...The results of the study suggest the effects are still detectable more than six months after the acute illness, and that any recovery is at best gradual.

“Cognitive impairment is common to a wide range of neurological disorders, but the patterns we saw – the cognitive ‘fingerprint’ of COVID-19 – was distinct from all of these.” — David Menon

....recovered patients reporting symptoms including fatigue, “brain fog,” difficulty recalling words, sleep disturbances, anxiety, and even post-traumatic stress disorder (PTSD) months after infection. In the United Kingdom, a research study found that one in every seven people surveyed reported having symptoms such as cognitive difficulties 12 weeks after a positive COVID-19 test.

...While even mild cases can lead to persistent cognitive symptoms, between a third and three-quarters of hospitalized patients report still suffering cognitive symptoms three to six months later...

https://scitechdaily.com/cognitive-impairment-from-severe-covid-19-equivalent-to...
_____________________________________________________

Adam Hampshire et al. 2022. Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort. (Lancet) eClinicalMedicine. Volume 47, 101417, May 01, 2022
DOI: 10.1016/j.eclinm.2022.101417 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00147-X/fullt...

37margd
mei 10, 2022, 5:58 pm

Gabriel Hébert-Mysterious™ 😎 (Breaking News Specialist) @Gab_H_R | 6:35 AM · May 10, 2022:

Well well well 🫠
Pediatric Acute Liver Failure Due to Type 2 Autoimmune Hepatitis Associated With SARS-CoV-2 Infection 👀
Age of patient: 3
Mysteriously published in April 2022...

Osborn, Julie MD et al. 2022. Pediatric Acute Liver Failure Due to Type 2 Autoimmune Hepatitis Associated With SARS-CoV-2 Infection: A Case Report. J of Pediatric Gastroenterology and Nutrition
(JPGN) Reports: May 2022 - Volume 3 - Issue 2 - p e204. doi: 10.1097/PG9.0000000000000204 https://journals.lww.com/jpgnr/fulltext/2022/05000/pediatric_acute_liver_failure...

Abstract
Although elevated liver enzymes are common in hospitalized children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, pediatric acute liver failure is an uncommon manifestation of COVID-19 disease. We describe the case of a 3-year-old previously healthy female who developed acute liver failure secondary to type 2 autoimmune hepatitis preceded by mild infection with SARS-CoV-2. Testing for viral hepatitis was negative, and the patient did not meet diagnostic criteria for multisystem inflammatory disease in children (MIS-C). A liver biopsy showed acute submassive hepatocyte necrosis with brisk CD3+ T lymphocyte infiltration and no evidence of fibrosis or chronic liver disease. Treatment with high-dose methylprednisolone resulted in rapid normalization of alanine aminotransferase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), and ammonia levels, and liver transplantation was avoided. This case highlights a possible association between SARS-CoV-2 infection and subsequent development of autoimmune liver disease presenting with acute liver failure.
________________________________________________

Lauren Pelley (CBC News) @LaurenPelley | 10:15 AM · May 10, 2022:
https://twitter.com/LaurenPelley/status/1524030311117508608

NEW: WHO says there are now 348 probable cases of acute hepatitis in children being investigated, with cases being reported in five different regions.
---------------------------------------------------------------------

Unexplained hepatitis cases in kids rise to 348 in 20 nations
Lisa Schnirring | News Editor | CIDRAP News | May 10, 2022
https://www.cidrap.umn.edu/news-perspective/2022/05/unexplained-hepatitis-cases-...

38margd
mei 11, 2022, 8:48 am

>37 margd: Uh oh?

David Fisman (U Toronto epidemiologist) @DFisman | 5:19 PM · May 10, 2022:

Anecdotally (reliable source) I’m hearing that some of the children with mystery hepatitis are now developing mystery aplastic anemia.

If you think liver transplants are no big deal, wait til you find out about the minor procedure called “bone marrow transplant”

39margd
mei 12, 2022, 9:02 am

>37 margd: contd.

I had difficulty registering to read (free). Will try again later:

Japanese researcher suggests ties between omicron variant and severe hepatitis in children
Tomoko Otake | 12 May 2022
https://www.japantimes.co.jp/news/2022/05/12/national/science-health/japanese-re...

40margd
mei 12, 2022, 1:38 pm

President Biden addressed the nation from the digital Global COVID-19 Summit, as America officially surpassed 1M deaths from the virus

Biden's Remarks on 1 Million Deaths From COVID-19 in the U.S.
President Biden addressed the nation from the digital Global COVID-19 Summit, as America officially surpassed 1M deaths from the virus

0:38 ( https://twitter.com/nowthisnews/status/1524799816248614919 )

- NowThis @nowthisnews | 1:13 PM · May 12, 2022

41margd
mei 14, 2022, 7:47 am

Petter Brodin (Prof Ped Immun, Imperial College) @BrodinPetter | 6:46 PM · May 13, 2022
Acute hepatitis in kids. We urge colleagues with access to samples (blood/liver tissue) to consider SARS-CoV-2 superantigen-mediated disease, potentiated by a second virus (AdV) 🧵1/

...6/ We should urgently investigate SARS-CoV-2 superantigen mediated disease, potentiated by an intestinal virus (AdV or other) as a possible mechanism of hepatitis. If confirmed, immunomodulatory treatments could be given and hopefully help.

( contd. https://twitter.com/BrodinPetter/status/1525246188404060161)
---------------------------------------------------------------------------------

Petter Brodin and Moshe Arditi. 2022. Severe acute hepatitis in children: investigate SARS-CoV-2 superantigens (Correspondence). The Lancet: Gastroenterology and Hepatology. Published:May 13, 2022DOI:https://doi.org/10.1016/S2468-1253(22)00166-2 https://thelancet.com/journals/langas/onlinefirsthttps://www.thelancet.com/journ...

Recently, there have been reports of children with a severe acute form of hepatitis in the UK, Europe, the USA, Israel, and Japan.1 Most patients present with gastrointestinal symptoms and then progress to jaundice and, in some cases, acute liver failure. So far, no common environmental exposures have been found, and an infectious agent remains the most plausible cause. Hepatitis viruses A, B, C, D, and E have not been found in these patients, but 72% of children with severe acute hepatitis in the UK who were tested for an adenovirus had an adenovirus detected, and out of 18 subtyped cases in the UK, all were identified as adenovirus 41F.1, 2 This is not an uncommon subtype, and it predominantly affects young children and immunocompromised patients. However, to our knowledge, adenovirus 41F has not previously been reported to cause severe acute hepatitis.

SARS-CoV-2 has been identified in 18% of reported cases in the UK and 11 (11%) of 97 cases in England with available data tested SARS-CoV-2 positive on admission; a further three cases had tested positive within the 8 weeks prior to admission.2 Ongoing serological testing is likely to yield greater numbers of children with severe acute hepatitis and previous or current SARS-CoV-2 infection. Eleven of 12 of the Israeli patients were reported to have had COVID-19 in recent months,3 and most reported cases of hepatitis were in patients too young to be eligible for COVID-19 vaccinations. SARS-CoV-2 infection can result in viral reservoir formation.4 SARS-CoV-2 viral persistence in the gastrointestinal tract can lead to repeated release of viral proteins across the intestinal epithelium, giving rise to immune activation.5 Such repeated immune activation might be mediated by a superantigen motif within the SARS-CoV-2 spike protein that bears resemblance to Staphylococcal enterotoxin B,6 triggering broad and non-specific T-cell activation. This superantigen-mediated immune-cell activation has been proposed as a causal mechanism of multisystem inflammatory syndrome in children.4 , 7

Acute hepatitis has been reported in children with multisystem inflammatory syndrome, but co-infection of other viruses was not investigated.8 We hypothesise that the recently reported cases of severe acute hepatitis in children could be a consequence of adenovirus infection with intestinal trophism in children previously infected by SARS-CoV-2 and carrying viral reservoirs (appendix). In mice, adenovirus infection sensitises to subsequent Staphylococcal-enterotoxin-B-mediated toxic shock, leading to liver failure and death.9 This outcome was explained by adenovirus-induced type-1 immune skewing, which, upon subsequent Staphylococcal enterotoxin B administration, led to excessive IFN-γ production and IFN-γ-mediated apoptosis of hepatocytes.9 Translated to the current situation, we suggest that children with acute hepatitis be investigated for SARS-CoV-2 persistence in stool, T-cell receptor skewing, and IFN-γ upregulation, because this could provide evidence of a SARS-CoV-2 superantigen mechanism in an adenovirus-41F-sensitised host. If evidence of superantigen-mediated immune activation is found, immunomodulatory therapies should be considered in children with severe acute hepatitis.

42margd
mei 16, 2022, 6:33 am

Greg Dore @GregDore2 | 4:02 AM · May 15, 2022:
Kirby Institute, UNSW Sydney: epidemiologist & infectious diseases physician; hepatitis C; hepatitis B; Covid; health & human rights for people who use drugs

Australia has had 340K reported Covid cases in children less than 10 yrs, but as yet no “outbreak” of severe acute hepatitis. That doesn’t mean no potential link to Covid. But, if linked it means either it’s incredibly rare or the co-infecting or facilitating agent hasn’t been here.

43margd
mei 16, 2022, 3:39 pm

Isabella Eckerle @EckerleIsabella | 5:23 AM · May 16, 2022:
Prof at Geneva Centre for Emerging Viral Diseases - Virologist, MD, DTM&H, mom - interests: emerging viruses, tropical medicine, bats & birds. Views are my own.

Hear, hear…#SARSCoV2 #COVID19 #children - maybe not the best idea to let children get infected with a new virus? Elevated liver enzymes and bilirubin’s following SARS-CoV-2 infection in children under 10 | medRxiv
------------------------------------------------------------------

Ellen K. Kendall et al. 2022. Elevated liver enzymes and bilirubin following SARS-CoV-2 infection in children under 10. MedRxiv 14 May 2022. doi: https://doi.org/10.1101/2022.05.10.22274866 https://www.medrxiv.org/content/10.1101/2022.05.10.22274866v1

This article is a preprint and has not been certified by peer review

Abstract
Recently, the Centers for Diseases and Control released a nationwide health alert about an increase in hepatitis cases of unknown origin in children, raising concern about potential sequelae of COVID-19 infection. In this study, we test whether there was increased risk of elevated serum liver enzymes and bilirubin following COVID-19 infection in children. We performed a retrospective cohort study on a nation-wide database of patient electronic health records (EHRs) in the US. The study population comprise 796,369 children between the ages of 1-10 years including 245,675 who had contracted COVID-19 during March 11, 2020 - March 11, 2022 and 550,694 who contracted non-COVID other respiratory infection (ORI) during the same timeframe.

Compared to children infected with other respiratory infections, children infected with COVID-19 infection were at significantly increased risk for elevated (liver enzymes) AST or ALT (hazard ratio or HR: 2.52,...) and total bilirubin (HR: 3.35). These results suggest acute and long-term hepatic sequelae of COVID-19 in pediatric patients. Further investigation is needed to clarify if post-COVID-19 related hepatic injury described in this study is related to the current increase in pediatric hepatitis cases of unknown origin.

44margd
mei 18, 2022, 6:27 am

Back of the envelope 17-post analysis "Comparing Masks and Ventilation/Filtration 🧵"

Joey Fox, P. Eng, M.A.Sc @joeyfox85 | 7:16 PM · May 17, 2022:
HVAC Engineer. Building Automation Systems. #COVIDisAirborne . Ventilation, Filtration, UVGI. If you know how it spreads, you know how to stop it.

Comparing Masks and Ventilation/Filtration (17-post)🧵
https://twitter.com/joeyfox85/status/1526703242578739200

What's more effective - a CR box in the classroom or everyone wearing a cloth mask? Here's how they can be compared. 1/17...

...To compare in a classroom setting:
- CR (Corsi Rosenthal) Box (275 CFM (cubic-feet-per-minute airflow)) is better than a surgical mask (250)
- Great ventilation 750 CFM (that's 6 ACH) + CR box is equal to 2-way surgical masking
- Upper room UV which is equivalent to 1600 CFM is better than a non-fit-tested respirator
10/17

There were a bunch of assumptions here and it's not a 100% fair comparison. For example, I used a poor (but common) ventilation of 250 CFM. If you have a room that is at modern standards, a surgical mask will provide the equivalent of an extra 400 CFM. (That's a lot)
11/17

Conversely, if you are in a really poorly ventilated room with 100 CFM (still common), a surgical mask will provide only an extra 100 CFM, like a medium size HEPA filter. A cloth mask will give you 33 CFM - barely anything. 2-way (universal) cloth masking is 78 CFM. Still minimal.
12/17

This all assumes consistent and proper masking.
Some important takeaways:
If you are indoors, there is no better option to protect against infection than a proper fitting respirator.
But respirators don't remove the virus, they only reduce the concentration you inhale.
13/17

Masks are the best tool against short range transmission. Initially when you breathe out, respiratory aerosols are more concentrated. Ventilation can help in that situation, but is less effective. Masks stop short range transmission.
14/17

For masks in schools - if kids are wearing cloth masks in a poorly ventilated room and not wearing them properly, a CR box or HEPA filter would be much more effective.
15/17

It shows the importance of air quality and how that amplifies the effectiveness of masks. It also shows why if there is masking, it should be respirators and not cloth masks.
This isn't one or the other, you can do both. But this is a rough comparison between them.
16/17

IMHO: This demonstrates that there is low benefit for mask mandates in poorly ventilated schools where cloth masks are allowed. Especially if not worn properly.
If you want an effective way to reduce transmission, you need respirators with good air quality.
17/17

(Q&A. Discussion)

45margd
mei 18, 2022, 6:33 am

Joey Fox, P. Eng, M.A.Sc @joeyfox85 | 8:09 PM · Feb 28, 2022:
HVAC Engineer. Building Automation Systems. #COVIDisAirborne . Ventilation, Filtration, UVGI. If you know how it spreads, you know how to stop it.

Intro to ultraviolet light against COVID (20-post) 🧵
https://twitter.com/joeyfox85/status/1498465352266752001

Ultraviolet light has many different applications. Here are 6 that have been used for COVID:

1. In-duct
2. Stand-alone
3. Upper Room
4. Far UV
5. Surface Sterilization
6. Photocatalytic Oxidation

TL;DR - See tweet 16 👇
1/20

...
1. In-duct or standalone - might work, but filtration is less expensive
2. Upper Room - amazing technology that requires more use
3. Far UV - great, but not widespread yet
4. Surface Sterilization - not helpful for COVID
5. UV PCO - Electronic air cleaner-Avoid
16/20

46margd
mei 18, 2022, 6:47 am

Biden administration makes 8 more free Covid tests available to US households as it calls on Congress to pass additional funding
Betsy Klein | May 17, 2022

...The Biden administration is opening CovidTests.gov for a third round of orders while reiterating its calls on Congress to act on additional Covid response funding.

US households are now able to order "an additional eight free at-home tests at COVIDTests.gov—bringing the total number of free tests available to each household since the start of the program to 16," the White House said in a fact sheet on Tuesday. The tests were first made available on Monday...

https://www.cnn.com/2022/05/17/politics/home-covid-tests/index.html

47margd
Bewerkt: mei 18, 2022, 7:28 am

Min Kyung Jung et al. 2022. BNT162b2*-induced memory T cells respond to the Omicron variant with preserved polyfunctionality. Nature Microbiology (16 May 2022) https://www.nature.com/articles/s41564-022-01123-x

Abstract
...Vaccine-induced memory T cells exhibited substantial responses to the Omicron spike protein, with no difference between healthcare workers with two versus three vaccine doses. In individuals with prior infection, two-dose vaccination robustly boosted memory T cells that responded to the Omicron spike protein and the SARS-CoV-2 wild-type (lineage B) spike protein. Importantly, polyfunctionality was preserved in vaccine-induced memory T cells responding to the Omicron spike protein. The present findings indicate that BNT162b2*-induced memory T cells substantially respond to the Omicron variant with preserved polyfunctionality.

* BioNTech, Pfizer vaccine

48margd
mei 18, 2022, 9:50 am

Eric Topol (Scripps) @EricTopol | 12:38 PM · May 4, 2022
A side benefit of the use of masks is reduction in dose of the virus exposed https://royalsocietypublishing.org/doi/10.1098/rsif.2021.0781
text-abstract ( https://twitter.com/EricTopol/status/1521891909412671488/photo/1 )

This was initially pointed out by Kimberly Prather and colleagues in a classic Science Magazine perspective early in the pandemic: https://science.org/doi/epdf/10.1126/science.abc6197
infographic-masks & exposure ( https://twitter.com/EricTopol/status/1521891909412671488/photo/1 )

49margd
Bewerkt: mei 19, 2022, 9:58 am

Michael Mina (frmr Harvard MD-scientist) @michaelmina_lab | 11:09 PM · May 17, 2022:

MANY clinicians have been so inundated about Paxlovid drug interactions that they simply don’t prescribe this life saving drug
But is the concern overblown?
Only 2 drugs (in a list of 100 most used) identified w such bad interactions that Paxlovid shouldnt be prescribed at all

Management of Drug Interactions With Nirmatrelvir/Ritonavir (Paxlovid®): Resource for Clinicians
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-ma...

The link from @IDSAInfo is a terrific resource for doctors, and other healthcare professionals to use when considering prescribing Paxlovid, including how to manage the dosing.
Highly recommend

Management of Drug Interactions With Nirmatrelvir/Ritonavir (Paxlovid®): Resource for Clinicians (4p)
IDSA COVID-19 TREATMENT AND MANAGEMENT GUIDELINE PANEL ON BEHALF OF
THE INFECTIOUS DISEASES SOCIETY OF AMERICA | May 6, 2022
https://idsociety.org/practice-guideline/covid-19-guideline-treatment-and-manage...

To clarify the note above *Only two drugs identified among a list of the 100 most used drugs*
There are many ppl who are on other drugs that will exclude Paxlovid
But the vast majority of people who can benefit from Paxlovid will not be disqualified for interactions
--------------------------------------------------------------------------------

Conan MacDougall (USCF prof) @ConanMacDougall | 11:17 PM · May 17, 2022
...Many of the patients who would benefit most from Paxlovid - eg transplant, chemotherapy patients - likely to be on drugs with significant interactions...

Michael Mina @michaelmina_lab | 11:37 PM · May 17, 2022
Agree.
Of the Majority of patients taking the majority of drugs, those on an entirely contraindicated drug are few and far between.
This isn’t to diminish the importance of serious drug interactions, but to help raise awareness that most ppl would not overtly be disqualified

Conan MacDougall @ConanMacDougall | 11:51 PM · May 17, 2022:
Absolutely & thanks for highlighting this great resource. If significant interactions identified, reach out for help as these interactions are complex!
Use of contraindicated drug to rescue from toxicity resulting from combining another drug with Paxlovid:

Dusten T. Rose et al. 2022. Supratherapeutic tacrolimus concentrations with nirmatrelvir/ritonavir in solid organ transplant recipients requiring hospitalization: A case series using rifampin for reversal. Open Forum Infectious Diseases, ofac238, Published: 13 May 2022. https://doi.org/10.1093/ofid/ofac238 https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac238/6585265

Accepted manuscript

Abstract
Nirmatrelvir/ritonavir was recently granted emergency use authorization for mild-moderate coronavirus disease 2019. Drug-drug interactions between ritonavir and tacrolimus are under-appreciated by non-transplant providers. We describe two solid organ transplant recipients prescribed nirmatrelvir/ritonavir for outpatient use that developed tacrolimus toxicity requiring hospitalization and were managed with rifampin for toxicity reversal.
------------------------------------------------------------------------

Michael Mina @michaelmina_lab | 11:56 PM · May 17, 2022:
Conan - Do any pharmacy societies have good overviews for physicians on Paxlovid prescriptions?
(On average, I trust pharmacists more than the physicians when it comes to expertise around interactions - it is sort of their specialty after all!)

Conan MacDougall @ConanMacDougall | 12:15 AM · May 18, 2022
Nothing as comprehensive as the IDSA guidelines that I know of. Luckily both IDSA & NIH guidelines have great ID pharmacists on their panels to provide that expertise. Also Liverpool drug interaction checker* is a great free resource. Cross-checking multiple sources helps!

Joseph Vassalotti, MD @Joe_Vassalotti · May 18
The IDSA resource is great, but does not include tacrolimus.
Ontario COVID-19 Science Advisory Table and University of Waterloo School of Pharmacy is another resource recommended in the NIH guidelines:
https://covid19-sciencetable.ca/sciencebrief/nirmatrelvir-ritonavir-paxlovid-wha...

*Rachel Ann Bender Ignacio, MD MPH (U Washington) @Drbenderignacio | 11:54 PM · May 17, 2022:
New favorite phone app from Liverpool https://covid19-druginteractions.org
Clinicians can download the phone app. I find more helpful as interactive and easy to use while calling a patient back

50margd
mei 20, 2022, 7:52 am

Shelly Miller, PhD @ShellyMBoulder | 2:18 AM · May 20, 2022:
Environmental engineering professor (U Colorado Boulder)

Our new paper investigates using modeling tools different mitigation strategies for a large office building. Should you increase your ventilation rate to 100%OA (Outside Air)? or use germicidal UV? Next paper will look at strategies for schools, retail and hotels.
------------------------------------------------------------------------

Shujie Yana Liangzhu et al. 2021. Evaluating SARS‐CoV‐2 airborne quanta transmission and exposure risk in a mechanically ventilated multizone office building. Building and Environment Volume 219, 1 July 2022, 109184 https://doi.org/10.1016/j.buildenv.2022.109184 https://www.sciencedirect.com/science/article/pii/S0360132322004206

Highlights
• A new method was developed for simulating SARS-CoV-2 airborne quanta transmission in multizone buildings using CONTAM.
• Whole-building exposure risk was modeled for a large office building , considering dynamic zone pressures and ambient conditions.
• System level mitigation was more effective to reduce overall building risk when the location of the infected individual was unknown.
• In-room mitigation reduced local transmission risk more effectively when the individual was in the same zone.

Abstract
The world has faced tremendous challenges during the COVID-19 pandemic since 2020, and effective clean air strategies that mitigate infectious risks indoors have become more essential. In this study, a novel approach based on the Wells-Riley model applied to a multizone building was proposed to simulate exposure to infectious doses in terms of “quanta”. This modeling approach quantifies the relative benefits of different risk mitigation strategies so that their effectiveness could be compared. A case study for the US Department of Energy large office prototype building was conducted to illustrate the approach. The infectious risk propagation from the infection source throughout the building was evaluated. Different mitigation strategies were implemented, including increasing outdoor air ventilation rates and adding air-cleaning devices such as Minimum Efficiency Reporting Value (MERV) filters and portable air cleaners (PACs) with HEPA filters in-room/in-duct germicidal ultraviolet (GUV) lights, layering with wearing masks. Results showed that to keep the risk of the infection propagating low the best strategy without universal masking was the operation of in-room GUV or a large industrial-sized PAC; whereas with masking all strategies were acceptable. This study contributes to a better understanding of the airborne transmission risks in multizone, mechanically ventilated buildings and how to reduce infection risk from a public health perspective of different mitigation strategies.

51margd
Bewerkt: mei 20, 2022, 8:37 am

President Biden @POTUS | 7:55 PM · May 19, 2022:
United States government official
The CDC just approved COVID-19 boosters for everyone five years and older. That means if you or your 5+ child were fully vaccinated in December or earlier, you should go get your first booster shot today.
----------------------------------------------------------

Ashish K. Jha, MD, MPH @AshishKJha46 | 9:41 PM · May 19, 2022:
White House COVID-19 Response Coordinator, physician, researcher...

Thrilled to see CDC's clear support for booster for 5-11 year-olds
Independent advisors reviewed the data, voted 11-1 in favor of supporting kids getting the booster
I have a 10-year-old so what do I plan to do?
Follow the evidence and get him boosted
Lets talk why

First, kids are way better off vaccinated than not
What? May be you've heard COVID "no big deal" for kids?
Obviously kids are lower risk than the elderly
But that's the wrong comparison
Kids are lower risk than elderly for pretty much everything
So the right question?

The right question is
How does COVID compare to other risks kids face?
And the 2nd right question is
How do the benefits of vaccines compare to the risks of vaccines?
Here, the answer are pretty clear
So first, here's some data on vaccine preventable diseases in kids
Table ( https://twitter.com/AshishKJha46/status/1527464456212697097/photo/1 )

Right, COVID is a lot more dangerous to kids than many other childhood illnesses for which we rightly vaccinate our kids
And the benefits of vaccinations for COVID?
They dramatically lower than risk of hospitalizations and deaths for children
But that's not all

Vaccines dramatically lower risk of Multisystem Inflammatory Syndrome in Children
And the risks of these vaccines in 5-11 years are trivial
Way less than risks from the complications of COVId
So what about a 3rd dose?
Evidence for Omicron is clear: a 3rd dose helps. A lot.

So if you have a 5-11 year-old at home
And that kiddo got their last dose 5 months ago or more
Its time for a 3rd dose
Infections are high
A 3rd dose provides real additional protection
That's why I'm getting my 10-year-old a boost
Thrilled to see CDC decision tonight
End

52margd
mei 20, 2022, 8:38 am

Michael Mina @michaelmina_lab | 10:18 PM · May 19, 2022:
(MD-scientist, frmr Harvard prof)

FYI: Many rapid tests have longer expiration dates than what’s on the box As they are on shelves longer, @US_FDA extends expiry They often last ~24 months and FDA is updating accordingly. Check the last column of the list for your test here.

https://fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/home-ot...

53margd
mei 20, 2022, 9:01 am

Eric Topol (Scripps) @EricTopol | 7:48 PM · May 17, 2022:
The "Delta" (L452R) mutation found in both the BA.2.12.1 and BA.4/BA.5 variants is key to both immune escape and enhanced cell fusion (not present in BA.1 or BA.2). And people with prior Delta infections have better neutralization to these variants
Table-mutations in variants ( https://twitter.com/EricTopol/status/1526711220429914113/photo/1 )
----------------------------------------------------

Panke Qu et al. 2022. Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants. BioRxiv 17 May 2022.
doi: https://doi.org/10.1101/2022.05.16.492158 https://biorxiv.org/content/10.1101/2022.05.16.492158v1

This article is a preprint and has not been certified by peer review

Summary
The rising case numbers of the SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 subvariants has generated serious concern about the course of the pandemic. Here we examine the neutralization resistance, infectivity, processing, and fusogenicity of spike from the BA.4/5 and BA.2.12.1 SARS-CoV-2 variants compared with other Omicron subvariants and Delta. Critically, we found that the new Omicron subvariants BA.4/5 and BA.2.12.1 were more resistant to neutralization by mRNA-vaccinated and boosted health care worker sera and Omicron-BA.1-wave patient sera than were the BA.1 and BA.2 variants. Interestingly, Delta-wave patient sera neutralized more efficiently against not only Delta but also BA.4/5 and BA.2.12.1 variants that also contain substitutions at position L452, similar to Delta. The BA.4/5 and BA.2.12.1 variants also exhibited higher fusogenicity, and increased spike processing, dependent on the L452 substitution. These results highlight the key role of the L452R and L452Q mutations in BA.4/5 and BA.2.12.1 subvariants.

54margd
mei 20, 2022, 9:19 am

Jan Choutka...& Akiko Iwasaki. 2022. Unexplained post-acute infection syndromes (Review). Nature Medicine volume 28, pages 911–923 (18 May 2022) https://www.nature.com/articles/s41591-022-01810-6

Abstract
SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine. The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis. In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses.

55margd
mei 20, 2022, 9:55 am

The Covid Capitulation
As the virus accelerates its evolution, humans retrogress
Eric Topol | 15 May 2022

...The real number of cases is likely at least 500,000 per day, far greater than any of the US prior waves except Omicron.

...Meanwhile, the CDC propagates delusional thinking that community levels are very low

...As of last week, 43% of new cases were attributable to BA.2.12.1...BA.2.12.1 is out-competing BA.2 with its 25% higher transmission rate, which foretells its further rise to dominance across the US in the days and weeks ahead.

...Why is the transition to BA.2.12.1 important?
...we have a highly unfavorable picture of:
(1) accelerated evolution of the virus;
(2) increased immune escape of new variants;
(2) progressively higher transmissibility and infectiousness;
(4) substantially less protection from transmission by vaccines and boosters;
(5) some reduction on vaccine/booster protection against hospitalization and death;
(6) high vulnerability from infection-acquired immunity only; and
(7) likelihood of more noxious new variants in the months ahead

...A Delusional Congress
...Congress should immediately allocate for an Operation Warp Speed (OWS)-like initiative to bring nasal vaccines over the goal line.

...From Zero Covid to Zero Covid Deaths...
...the pandemic is far from over. Our Covid vaccines and medications are an order of magnitude more effective than what we have for influenza, but even our current level of deaths (we have already had over 175,000 Covid deaths in 2022), no less what may be in store, is still more than 10-fold in excess of seasonal flu (about 30,000 per year). That is totally unacceptable, nearly totally preventable loss of lives at scale....

https://erictopol.substack.com/p/the-covid-capitulation

56margd
mei 21, 2022, 10:03 am

"...a highly contagious (although relatively milder) SARS-CoV-2 variant can quickly confer substantial excess mortality, even in a highly vaccinated and increasingly immune population..."

Jeremy Samuel Faust et al. 2022. Excess Mortality in Massachusetts During the Delta and Omicron Waves of COVID-19 (Research Letter). JAMA. Published online May 20, 2022. doi:10.1001/jama.2022.8045 https://jamanetwork.com/journals/jama/article-abstract/2792738

...Discussion
More all-cause excess mortality occurred in Massachusetts during the first 8 weeks of the Omicron period than during the entire 23-week Delta period. Although numerically there were more excess deaths in older age groups, there was excess mortality in all adult age groups, as recorded in earlier waves, including in younger age groups... Moreover, the ratio of observed to expected all-cause deaths was similar in all age groups, and increased during the Omicron period compared with the Delta period.

Others have reported that the Omicron variant may cause milder COVID-19. If true, increased all-cause excess mortality observed during the Omicron wave in Massachusetts may reflect a higher mortality product (ie, a moderately lower infection fatality rate multiplied by far higher infection rate).

This observational study was limited by use of preliminary data, although mortality reporting for the study period in Massachusetts is more than 99% complete. Also, during the early Omicron period, a small number of deaths may have been caused by Delta infections that occurred several weeks earlier. Nevertheless, the present findings indicate that a highly contagious (although relatively milder) SARS-CoV-2 variant can quickly confer substantial excess mortality, even in a highly vaccinated and increasingly immune population.

57margd
mei 21, 2022, 10:23 am

Manoj Sivan et al. 2022. Are vaccines a potential treatment for long covid? ( Editorial ) BMJ 2022;377:o988 (Published 18 May 2022) doi: https://doi.org/10.1136/bmj.o988 https://www.bmj.com/content/377/bmj.o988

Benefits are possible, but we need more evidence and a mechanism of action
-------------------------------------------------------------

Daniel Ayoubkhani et al. 2022. Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study. BMJ 2022;377:e069676 (Published 18 May 2022) doi: https://doi.org/10.1136/bmj-2021-069676 https://www.bmj.com/content/377/bmj-2021-069676

Abstract
...Conclusions The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.

58margd
Bewerkt: mei 21, 2022, 10:43 am

Michael Lin, MD PhD 🧬 (Stanford) @michaelzlin | 7:56 PM · May 17, 2022:
WHO is convincing me to be more enthusiastic about 4th doses.
Today they reviewed studies showing dose 4 gives 60yo and older a 60% more protection from severe disease over dose 3, or an increase in absolute VE (vaccine effectiveness) from 82% to 92%.
That's a meaningful improvement.
------------------------------------------------

Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19
WHO | 17 May 2022

https://www.who.int/news/item/17-05-2022-interim-statement-on-the-use-of-additio...

59margd
mei 22, 2022, 4:34 am

Dr. Lisa Iannattone @lisa_iannattone | 9:51 PM · May 20, 2022:
Prof dermatology, U Montreal
“Reinfections are rare” 🚩
33.5% of daily infections in Quebec are reinfections.
And 40% of those had already had covid between Dec ‘21 and April ‘22.

So we have 4700 to 7700 reinfections a day, of which 1900 to 3000 *a day* already had covid b/w Dec 21 and April 22.
Rare 🚩🙃

Quote Tweet
CIRANO @CIRANOMTL | 5:00 AM · May 20, 2022:
Baisse de l’incidence des cas de COVID-19 au Québec pour cette 18e et dernière semaine de collecte (12 au 17 mai) selon l’étude #CIRANO. Entre 14 000 et 23 000 cas par jour
( Google translate: Decrease in the incidence of COVID-19 cases in Quebec for this 18th and last week of collection (May 12 to 17) according to the study #CIRANO . Between 14,000 and 23,000 cases per day )

Graph incidence over time Quebec ( https://twitter.com/CIRANOMTL/status/1527575050630701056/photo/1 )

Étude exploratoire pour évaluer l'incidence de la COVID-19 au Québec - Mise à jour avec les données de la semaine du 12 au 17 mai 2022
(Google translate: Exploratory study to assess the incidence of COVID-19 in Quebec - Updated with data for the week of May 12 to 17, 2022)
20 mai 2022
https://cirano.qc.ca/fr/actualites/1081

60margd
mei 23, 2022, 7:56 am

Pfizer covid shot 80 percent effective in young kids, early data shows
Carolyn Y. Johnson | May 23, 2022

Pfizer and its German partner, BioNTech, said Monday that an early analysis showed their three-dose coronavirus vaccine regimen triggered a strong immune response in young children, proving 80 percent effective at preventing symptomatic infections in children 6 months to 4 years old.

The results, along with other recent developments, signal that the long and frustrating wait for a vaccine for the youngest children, the last group to lack access, could be over within weeks...

https://www.washingtonpost.com/health/2022/05/23/children-coronavirus-vaccine-pf...

61margd
mei 24, 2022, 4:51 pm

Joey Fox, P. Eng, M.A.Sc@joeyfox85 | 4:56 PM · May 23, 2022:
HVAC Engineer. Building Automation Systems. #COVIDisAirborne . Ventilation, Filtration, UVGI. If you know how it spreads, you know how to stop it. (Toronto)
With links at https://twitter.com/joeyfox85/status/1528842332451360768

The best and worst engineering methods to stop COVID Not all methods are created equal. I'm ranking all the engineering methods to stop COVID based on how effective they are. We'll start with the worst things you can do... 1/21

1. The worst thing you can do: Fogging/Spraying Disinfectant. DO NOT DO THIS! The chemicals you spray in the air land on surfaces and are supposed to disinfect them. It's really bad for you and doesn't stop the spread of COVID. Just don't. 2/21

2. Next worst thing is electronic air cleaning. There's poor evidence it's effective in a real world setting and it can create harmful byproducts. Dry hydrogen peroxide, photocatalytic oxidation, ionization, plasma, hydroxyl, ozone... Stay away. 3/21

3. Frequent filter changes. This is something that costs money and effort, but actually makes filters less effective. ASHRAE recommends against it. Nevertheless, everyone is doing it. You can stop. 4/21

4. Surface cleaning - this includes shining UV light in the room when it's unoccupied and anything a cleaning company will do. COVID is airborne. Clean the air, not surfaces. 5/21

5. Flushing buildings at night. This doesn't hurt, but doesn't help and wastes a lot of energy. It should also be stopped. 6/21

Most places have 1-2 air changes/hour (ACH). Modern minimums are 3-4 ACH. Good air quality is 4-6+ ACH. Filtration and UV use equivalent ACH (eACH). Same effect for COVID. Now the 11 best ways to clean the air and prevent the spread of COVID (IMO). 7/21

11. Flushing rooms between occupancies. If a room will be reoccupied within the next couple of hours, leave the HVAC running. This can help a little. It's not one of the more effective measures, but should still be done. 8/21

10. In duct UV - this can add 1-3 eACH. UV lights are placed either by the coil or in the supply duct of the air handling unit to inactivate virus particles supplied to the space. 9/21
9. Increasing outdoor air % - this can add 0.5-5 ACH. It's more difficult supplying higher amounts of outdoor air in cold weather. It uses up energy to heat up or cool down the extra air. Still a helpful tool. https://twitter.com/joeyfox85/status/1527118643749965827?s=20&t=twzLDcdPpS5Z... 10/21

8. Upgrade the filter in the air handling unit to MERV-13. This adds 2.5-3 eACH and doesn't use up much more energy. You need to be careful not to affect the heating and cooling, but it's usually not a concern. 11/21

The three previous air cleaning methods - in-duct UV, increasing outdoor air % and MERV-13 filters all clean recirculated air. They all take place in the air handling unit and not in the space. I refer to them here as "out of room mitigation" 12/21

They are less effective: - they don't work together. It cleans the same air, so there are diminishing returns. - if the return air comes from a large area, there's a low amount of virus because of dilution. Onto the most effective methods: 13/21

7. Humidification. It's difficult to estimate an equivalent ACH for humidity control. It makes the viruses inactivate faster, deposit faster on surfaces (out of the air) and improves your own immune system. Unfortunately, it's rarely used. 14/21

6. Stand-alone UV air purification. This can add 2-3 eACH per unit. It's UV in a box with a fan. Many of these come with photocatalytic oxidation (bad) or a HEPA filter - which makes them redundant. Once you filter it out, it's gone. 15/21

5. Stand-alone HEPA filter or Corsi Rosenthal Box. This can add 2-3 eACH per unit. The cheapest consistent way to improve air quality. 16/21

4. Open windows. Also open the door and use a fan to push air from the window and out the door. It will be a lot of flow. The main problem is it can't be done when it's cold outside. It's difficult to calculate the exact flow from windows. 17/21

3. Ventilation Improvements. Good ventilation can provide between 3-6 ACH. All the previously mentioned strategies are inferior to having a building with good ventilation. I can't overstate the importance of investing in upgrading ventilation. 18/21
2. Upper Room UVGI ( Upper-Room Ultraviolet Germicidal Irradiation) - the real deal. It can add 12-24 eACH. It reduced measles outbreaks by 75%. If we want to go all out on mitigating airborne spread, this technology is needed. https://time.com/6143799/covid-19-indoor-air-cleaning/ 19/21

1. Far UV - I've seen estimates between 10-300+ eACH. This technology isn't widespread yet and still expensive, but it could be a game changer moving forward. 20/21

Vaccines protect you from severe disease. Rapid tests reduce your exposure to infected and highly infectious people. Wear a respirator indoors. Spend more time outdoors. Besides that, DO EVERYTHING! 21/21

Additional Resources:...

62margd
mei 25, 2022, 1:30 pm

Vaccines may not prevent many symptoms of long covid, study suggests
Ariana Eunjung Cha | May 25, 2022 a

Veterans Affairs analyzed records from nearly 34,000 people in U.S. who experienced breakthrough infections

A large U.S. study looking at whether vaccination protects against long covid showed the shots have only a slight protective effect: Being vaccinated appeared to reduce the risk of lung and blood clot disorders, but did little to protect against most other symptoms.

The new paper, published Wednesday in Nature Medicine, is part of a series of studies by the Department of Veterans Affairs on the impact of the coronavirus, and was based on 33,940 people who experienced breakthrough infections after vaccination...

https://www.washingtonpost.com/health/2022/05/25/long-covid-vaccines-slight-prot...
----------------------------------------------------------------

Ziyad Al-Aly et al. 2022. Long COVID after breakthrough SARS-CoV-2 infection. Nature Medicine (25 May 2022) https://www.nature.com/articles/s41591-022-01840-0

Abstract
The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75...) and incident post-acute sequelae (HR = 1.50...), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders. The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66...) and incident post-acute sequelae (HR = 0.85...). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.

...Discussion
...In sum, our findings provide evidence of increased risk of death and post-acute sequelae in people with BTI compared to controls with no evidence of SARS-CoV-2 infection; the risks were reduced in comparative analyses involving BTI versus SARS-CoV-2 infection without prior vaccination. Our results show that SARS-CoV-2 vaccination before infection only partially reduced the risk of death and post-acute sequelae. Measures for the prevention of breakthrough infections are needed to most optimally reduce the risk of the long-term health consequences of SARS-CoV-2 infection...

63margd
mei 25, 2022, 1:44 pm

People who rebound with COVID-19 after Paxlovid may be highly contagious, new studies suggest
The findings come as federal regulators issue warning about Paxlovid rebound
Kay Lazar | May 24, 2022

Federal health regulators on Tuesday issued a warning that COVID-19 patients who have taken the antiviral treatment Paxlovid may experience a rebound and test positive again two to eight days after initial recovery.

The warning comes more than a month after droves of patients began swapping accounts on social media of COVID rebounds after taking Paxlovid.

The alert from the Centers for Disease Control and Prevention said it continues to recommend Paxlovid for patients at high risk for serious complications from infection. It also said that people with a recurrence of COVID-19 symptoms, or a new positive test after having tested negative, should isolate again for at least five days. It added that people should wear a mask for a total of 10 days after rebound symptoms start...

The CDC warning comes as two small but provocative new studies from different teams of researchers in Boston and New York suggest such relapses may not be that unusual. The scientists also found that, in some rebound patients, viral levels were likely high enough to be contagious...

https://www.bostonglobe.com/2022/05/24/metro/people-who-rebound-with-covid-19-af...
----------------------------------------------------------------------

COVID-19 Rebound After Paxlovid Treatment
CDC HEALTH ADVISORY | May 24, 2022, 9:00 AM ET
CDCHAN-0467 (4 p)

...Recommendations for the Public
• You may be experiencing COVID-19 rebound if you have been diagnosed in the past 2 weeks
and have recovered from COVID-19 and then experience recurrent COVID-19 symptoms or
develop newly positive test results after recovery.
• If you experience COVID-19 rebound, you should follow CDC’s isolation guidance. Isolate again
and restart the recommended 5-day isolation period at the time of recurrence of symptoms or a
new positive COVID-19 test result. You can end re-isolation after 5 days if you are fever-free for
24 hours without the use of fever-reducing medication and your symptoms are improving. You
should also wear a mask for 10 days after rebound.
• Contact a healthcare provider if your COVID-19 rebound symptoms persist or worsen.
• Consult with your healthcare provider if you have additional questions about your treatment.
• You are encouraged to report a possible case of COVID-19 rebound after Paxlovid treatment to
Pfizer using the following online tool: Pfizer Safety Reporting...

https://emergency.cdc.gov/han/2022/pdf/CDC_HAN_467.pdf
-----------------------------------------------------------------------------

Michael Charness et al. 2022. Rapid Relapse of Symptomatic Omicron SARS-CoV-2 Infection Following Early Suppression with Nirmatrelvir/Ritonavir (Case report) Research Square https://doi.org/10.21203/rs.3.rs-1588371/v3 https://www.researchsquare.com/article/rs-1588371/v3

Preprint

64margd
Bewerkt: mei 27, 2022, 7:45 am

We have a virus ripping through this country at an infectious rate bordering on measles that is giving 1 in 5 people a new health condition - and we have zero mitigation efforts in place.

It sounds so crazy to say that out loud.

I'm not pro "lock-downs", but it's incredibly eerie that China has made the decision that protecting their population from infection **far outweighs** any short-term economic hit from that decision.

It makes you wonder what they are seeing in their #LongCovid data.

In addition, how many premature heart attacks, strokes, and early on-set dementia are we going to see in 5-10-20 years from this? It's going to be absolutely devastating. #LongCovid

- charlos @loscharlos | 4:19 PM · May 26, 2022
https://twitter.com/loscharlos/status/1529920059530850305

65margd
mei 27, 2022, 8:52 am

Uh oh?
BA.4/BA.5: restored fusogenicity (delta) + immune evasiveness (omicron)?
Buckle your facemasks?

Dr. Lisa Iannattone @lisa_iannattone | 9:47 PM · May 26, 2022:
Assistant Professor of Dermatology @med_umontreal . Adjunct Clinical Professor @McGillMed . Former Harvard derm fellow. Focus: complex medical dermatology.
https://twitter.com/lisa_iannattone/status/1530002665815539715

The new BA.4/BA.5 data is bad. No one outside of Twitter is going to say it out loud. And even here on Twitter, the Science Twitter Panic Police™️ will be along shortly to scold those of us that dare tweet on early data that isn’t good news.
▶️Wear your masks.
▶️Weigh your risks.

---------------------------------------------------------------------------

Quote Tweet
The Sato Lab (Kei Sato) @SystemsVirology | 6:30 PM · May 26, 2022:
Division of Systems Virology, Institute of Medical Science, University of Tokyo, Japan. G2P-Japan Consortium主宰.
https://twitter.com/SystemsVirology/status/1529953265017757696

BREAKING🔔 The 10th preprint* from G2P-Japan🇯🇵 is out at @biorxivpreprint . #Omicron BA.4 & BA.5 variants seem to be more contagious and pathogenic than BA.2 variant. Please RT. 1/7...

▶️ Altogether, our multiscale investigations suggest that the risk of BA.4/5 for global health can be potentially higher than that of BA.2. 7/7

* Izumi Kimura et al. 2022. Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5. biorxiv.org 26 May 2022. doi: https://doi.org/10.1101/2022.05.26.493539 https://www.biorxiv.org/content/10.1101/2022.05.26.493539v1

Pre-print. Not yet peer-reviewed.

Abstract
After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2.


66margd
jun 1, 2022, 10:30 am

‘It hugs your soul!’ 10 dishes to get you fighting fit after an illness,
from ramen noodles to spicy tom yum soup
Leah Harper | Fri 25 Mar 2022

Whether you’re getting over Covid, or just a nasty cold, these comforting recipes from top chefs will lift your spirits

Roast chicken with lentils and kale
Fish curry with maize
Ramen noodles
Ginseng chicken soup
Tinned tomatoes on toast with grated cheese
Paya
Thai tom yum soup
Beans on toast with pesto and parmesan
Kadhi
Stir-fried greens

https://www.theguardian.com/lifeandstyle/2022/mar/25/it-hugs-your-soul-10-dishes...

67margd
Bewerkt: jun 2, 2022, 9:13 am

During the Omicron Wave, Death Rates Soared for Older People
Benjamin Mueller and Eleanor Lutz | May 31, 2022

Last year, people 65 and older died from Covid at lower rates than in previous waves. But with Omicron and waning immunity, death rates rose again.

...For older people...: So many of the most fragile Americans were killed by Covid over the winter that the virus now has fewer targets in that age group.

...As of mid-May, more than one-quarter of Americans 65 and older had not had their most recent vaccine dose within a year. And more than half of people in that age group had not been given a shot in the last six months.

The Omicron variant was better than previous versions of the virus at evading those already weakening immune defenses, reducing the effectiveness of vaccines against infection and more serious illness. That was especially true for older people, whose immune systems respond less aggressively to vaccines in the first place...

https://www.nytimes.com/2022/05/31/health/omicron-deaths-age-65-elderly.html

68margd
jun 5, 2022, 6:48 pm

COVID vaccines do not impact fertility or pregnancy outcomes, study shows
Bill Hathaway | May 24, 2022
https://news.yale.edu/2022/05/24/covid-vaccines-do-not-impact-fertility-or-pregn...

Alice Lu-Culligan...Akiko Iwasaki. 2022. No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination. PLOS Biology: May 24, 2022.
https://doi.org/10.1371/journal.pbio.3001506 https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001506

Abstract
The impact of Coronavirus Disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated 2 of the most widely propagated claims to determine (1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities; and (2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from these murine pregnancies vaccinated prior to the formation of the definitive placenta exhibit high circulating levels of anti-spike and anti-receptor-binding domain (anti-RBD) antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) consistent with maternal antibody status, indicating transplacental transfer in the later stages of pregnancy after early immunization. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.

69margd
Bewerkt: jun 6, 2022, 7:32 am

Michael Saag. 2022. Wonder of wonders, miracle of miracles: the unprecedented speed of COVID-19 science (Editorial). Physiology. 01 Jun 2022 https://doi.org/10.1152/physrev.00010.2022 https://journals.physiology.org/doi/full/10.1152/physrev.00010.2022

1. INTRODUCTION
2. A TALE OF TWO EPIDEMICS (HIV v COVID)
3. HOW DID THIS HAPPEN?
4. FOR SARS-COV-2, THE PAST IS PROLOGUE

...the activities of many COVID-19 activists have undermined scientific discovery, sewn doubt regarding the veracity of the scientific method, and created confusion among the public through the release and promotion of misinformation, disinformation, and outright falsehoods on social media outlets and talk radio. Unlike the AIDS activists who celebrated the science and pushed the field forward, many of these COVID-19 activists promote therapies that have minimal or no efficacy, especially when compared to monoclonal antibodies, nirmatrelvir/ritonavir, and molnupiravir, and espouse antivaccination rhetoric on social media .... This has contributed to 35% to 40% of the population in the United States choosing not to be vaccinated. Unvaccinated persons make up more than 80% of hospitalized patients and result in more than a 20-fold increase in death... Since the widespread release of vaccination, most of the deaths due to COVID-19 are preventable... An outcome that is antithetical to the efforts of activists in the AIDS era.

The most pernicious and destructive activity, however, is the “assassination of the Trusted Voice.” Throughout the COVID-19 crisis public health leaders, who normally are sought to provide guidance to the public regarding the best ways forward during Public Health emergencies in order to minimize sickness, death, and the impact on the healthcare delivery system, are maligned via social media and attacked personally, often in the form of serious threats on their lives and the well-being of members of their family... The societal cost of these activities are difficult to calculate precisely, but are enormous.

As the COVID-19 pandemic transforms into an endemic state, an analysis of the role COVID-19 activists have played in creating harm should be performed. Simultaneously, efforts should be directed at rehabilitating Public Health in providing guidance to the population during future crises.

In the meantime, the science that began decades ago in the battle against HIV and other viral diseases and formed the platform upon which the remarkable success of the development of COVID-19 prevention, vaccines, and therapeutics should be celebrated. Communication of this story to the public can be a catalyst for the reestablishment of trust in our Public Health System and its leaders.

___________________________________________

Yoni Maisel @Primary_Immune:
Vaccines, sequencing, data science, epidemiology, drug discovery, clinical trials - all at new speed.
Not mentioned, so I will mention it - the explosion of PREPRINTS in the early dissemination of life-saving data and research findings.

Prof. Akiko Iwasaki @VirusesImmunity
Absolutely! Thank you for spreading this important message, Yoni! @biorxivpreprint @medrxivpreprint have played a key role in disseminating critical & timely information during the pandemic and have changed the way we communicate scientific data.

70margd
jun 7, 2022, 7:19 am

How long covid could change the way we think about disability
Frances Stead Sellers | June 6, 2022

...The coronavirus pandemic has created a mass-disabling event that experts liken to HIV, polio or World War II, with millions suffering the long-term effects of infection with the virus. Many have found their lives dramatically changed and are grappling with what it means to be disabled.

...As many as 61 million, or 1 in 4, U.S. adults live with some form of disability, according to the Centers for Disease Control and Prevention. Those numbers are being bolstered by between 7 million and 23 million long-haulers — including 1 million who can no longer work — according to recent government estimates. Think tanks and others expect the numbers to rise as covid settles in as an endemic disease...

https://www.washingtonpost.com/health/2022/06/06/long-covid-disability-advocacy/

71margd
jun 7, 2022, 4:23 pm

Pfizer’s COVID Vaccine Protection Against Omicron Fades After a Few Weeks: Study
Jack Phillips | May 16, 2022
https://www.theepochtimes.com/pfizers-covid-vaccine-protection-against-omicron-f...
------------------------------------------------------------

Ria Lassaunière et al. 2022. Neutralizing Antibodies Against the SARS-CoV-2 Omicron Variant (BA.1) 1 to 18 Weeks After the Second and Third Doses of the BNT162b2 mRNA Vaccine ( Research Letter).
JAMA Netw Open. 13 May 2022;5(5):e2212073. doi:10.1001/jamanetworkopen.2022.12073

...Discussion
SARS-CoV-2 neutralizing antibodies are correlated with protection against infection and disease...Our study found a rapid decline in Omicron-specific serum neutralizing antibody titers only a few weeks after the second and third doses of BNT162b2. A limitation of our study is that its cross-sectional design precludes evaluation of antibody decrease rates on an individual level. Nevertheless, the observed decrease in population neutralizing antibody titers corresponds to the decrease in vaccine efficacy against polymerase chain reaction–confirmed Omicron infection in Denmark and symptomatic Omicron infection in the United Kingdom... Taken together, vaccine-induced protective antibody responses following a second and third dose of BNT162b2 are transient and additional booster doses may be necessary, particularly in older people; however, conserved T-cell immunity and nonneutralizing antibodies may still provide protection against hospitalization and death.

72margd
jun 7, 2022, 5:20 pm

Babies Exposed to COVID in the Womb Show Neurodevelopmental Changes
Featured Neuroscience · June 6, 2022

Summary: Babies whose mothers contracted COVID-19 while pregnant had greater difficulties relaxing and adapting their bodies while being held than those whose mothers did not contract covid. Additionally, babies born to infected mothers had greater difficulty in controlling their head and shoulder movements. Findings suggest prenatal COVID-19 infection may impact motor function development in babies.

Source: European Psychiatric Association

https://neurosciencenews.com/covid-motor-development-20763/

73margd
jun 8, 2022, 11:14 am

Justin J. Frere et al. 2022. SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations post recovery. Science Translational Medicine, 7 Jun 2022. DOI: 10.1126/scitranslmed.abq3059 https://www.science.org/doi/10.1126/scitranslmed.abq3059

Abstract
The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely impacted the olfactory bulb (OB) and epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month post viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

74margd
Bewerkt: jun 9, 2022, 9:18 am

Joey Fox, P. Eng, M.A.Sc @joeyfox85 | 6:51 PM · Jun 8, 2022:
HVAC Engineer. Building Automation Systems. #COVIDisAirborne . Ventilation, Filtration, UVGI. If you know how it spreads, you know how to stop it. (Toronto)
🧵 https://twitter.com/joeyfox85/status/1534669593268166657

Reducing COVID risk in a hotel (apartments too)

The three things you should do are:
1. Verify the building ventilation is working
2. Clean the air in your suite
3. Possibly block the airflow through the door (see below) 1/8

Verify the ventilation is working

The standard way ventilation systems work in hotels and apartment buildings is outdoor air is supplied to the hallway, flows under the door and is exhausted through the washroom. Here's how to check the ventilation: 2/8
https://twitter.com/joeyfox85/status/1534669626558369793/photo/1

1. Use a CO2 monitor. If it's high, you know something is wrong.
2. Go into the hallway and ensure air is being supplied. You can hold the CO2 monitor to the supply air and measure the CO2 being supplied. It should be around 420 ppm (100% outdoor air) 3/8
3. Hold a tissue to the exhaust grille in the washroom and ensure that air is being exhausted.
4. Check to make sure air is flowing under the door.

There might be units in the room for heating and cooling, but they only recirculate air. No ventilation. 4/8

If there are issues with any of this, notify the front desk.

Clean the air in the suite

Open windows and run a HEPA filter. It's best to place it near the door so you are filtering the air that is entering from the hallway. 5/8

If the windows don't open and the system is working properly, it will be detrimental to block the door. Air is exhausted through the washroom and has to be replenished from somewhere. 6/8

If it doesn't come through the door, it could leak in through the walls of a different suite. So here's the rule:
- If the windows aren't open and the system is working (airflow through the door and up the exhaust) then do not block the door. 7/8
- If you have the windows open or the system isn't working (no air going through the exhaust), then block the door.

If you are blocking the airflow through the door, use painters tape around the door cracks to stop the airflow. 8/8
--------------------------------------------------------------

Steven Mathern @StevenMathern
i wish i understood these instructions; ventilation experts assume i am not ignorant ;)

Joey Fox, P. Eng, M.A.Sc @joeyfox85
Step 1: go into the hallway and find a diffuser. Sometimes it's on the wall and sometimes on the ceiling. Is air coming out? Feel it with your hand.
https://twitter.com/joeyfox85/status/1534692974029852673/photo/1

Step 2: There should be a return grille in the bathroom. Hold up a tissue, does it get sucked in?
https://twitter.com/joeyfox85/status/1534693201788944384/photo/1

Step 3: Put a tissue by the bottom of the door, does the air come in from the hallway?

If the systems are working and you cannot open your windows, then do not block the door with tape.
If you can open the hotel windows or the systems aren't working properly, then you can block the door with tape.

(In comments, someone recommended painters' tape.)

75margd
jun 9, 2022, 10:14 am

Eric Topol @EricTopol | 7:01 AM · Jun 8, 2022
An Omicron (BA.1) specific booster hits immunologic and safety endpoints in a Phase 2/3 trial compared with ancestral strain booster, expected to be available in late summer/fall; @moderna_tx
release, attached

Highlighted text, Moderna release ( https://twitter.com/EricTopol/status/1534490672744394752/photo/1 )

76margd
jun 9, 2022, 10:54 am

Anneli Uusküla et al. 2022. Long-term mortality following SARS-CoV-2 infection: A national cohort study from Estonia. The Lancet April 28, 2022 DOI:https://doi.org/10.1016/j.lanepe.2022.100394 https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(22)00087-4/fullt...

SUMMARY
...Findings
People infected with SARS-COV-2 had more than three times the risk of dying over the following year compared with those who remained uninfected (aHR 3·1...). Short-term mortality (up to 5 weeks post-infection) was significantly higher among COVID-19 group (1623·0/10 000) than in the reference group (118/10 000). For COVID-19 cases aged 60 years or older, increased mortality persisted until the end of the first year after infection, and was related to increased risk for cardiovascular (aHR 2·1...), cancer (aHR 1·5...), respiratory system diseases (aHR 1·9...), and other causes of death (aHR 1·8...).

Interpretation
Increased risk of death from SARS-CoV-2 is not limited to the acute illness: SARS-CoV-2 infection carries a substantially increased mortality in the following 12 months. This excess death mainly occurs in older people and is driven by broad array of causes of death...

77margd
jun 11, 2022, 8:35 am

We Need to Improve Indoor Air Quality: Here’s How and Why
Tanya Lewis | June 8, 2022

Upgrading buildings’ ventilation, filtration and other factors would not only decrease COVID transmission but also improve health and cognitive performance in general...

https://www.scientificamerican.com/article/we-need-to-improve-indoor-air-quality...

https://www.scientificamerican.com/article/we-need-to-improve-indoor-air-quality...

78margd
jun 11, 2022, 8:57 am

Aerosol particles emitted increase 132X during physical education in school, dance events during weddings, high-intensity gym classes such as spinning. Hockey?

Benedikt Mutsch et al. 2022. Aerosol particle emission increases exponentially above moderate exercise intensity resulting in superemission during maximal exercise. PNAS May 23, 2022
119 (22) e2202521119 https://doi.org/10.1073/pnas.2202521119 https://www.pnas.org/doi/full/10.1073/pnas.2202521119

Significance
Airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other pathogens is probably increased during indoor exercise, but data on the emission of aerosol particles by an exercising individual are lacking. Here, we report that aerosol particle emission increases on average 132-fold from 580 ± 489 particles/min at rest to 76,200 ± 48,000 particles/min during maximal exercise. Aerosol particle emission increases moderately up to an exercise intensity of ≈2 W/kg and exponentially at higher exercise intensities. These data not only explain SARS-CoV-2 transmissions during indoor group exercise but also can be used to design better targeted mitigation measures for physical activity indoors such as physical education in school, dance events during weddings, or high-intensity gym classes such as spinning.

Abstract
Many airborne pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are transmitted indoors via aerosol particles. During exercise, pulmonary ventilation can increase over 10-fold, and therefore, exercisers will exhale a greater volume of aerosol-containing air. However, we currently do not know how exercise affects the concentration of aerosol particles in exhaled air and the overall emission of aerosol particles. Consequently, we developed a method to measure in parallel the concentration of aerosol particles in expired air, pulmonary ventilation, and aerosol particle emission at rest and during a graded exercise test to exhaustion. We used this method to test eight women and eight men in a descriptive study. We found that the aerosol particle concentration in expired air increased significantly from 56 ± 53 particles/liter at rest to 633 ± 422 particles/liter at maximal intensity. Aerosol particle emission per subject increased significantly by a factor of 132 from 580 ± 489 particles/min at rest to a super emission of 76,200 ± 48,000 particles/min during maximal exercise. There were no sex differences in aerosol particle emission, but endurance-training subjects emitted significantly more aerosol particles during maximal exercise than untrained subjects. Overall, aerosol particle emission increased moderately up to an exercise intensity of ∼2 W/kg and exponentially thereafter. Together, these data might partly explain superspreader events especially during high-intensity group exercise indoors and suggest that strong infection prevention measures are needed especially during exercise at an intensity that exceeds ∼2 W/kg. Investigations of influencing factors like airway and whole-body hydration status during exercise on aerosol particle generation are needed.

79margd
Bewerkt: jun 11, 2022, 10:08 am

>72 margd: contd. In utero COVID exposure and neurodevelopmental disorders

Vaccines were available much later for pregnant women, so won't know for a while yet if babies exposed to vaccine in pregnancy will show neurodevelopmental disorders in the first year of life?

Shematologist, MD @acweyand | 8:46 PM · Jun 9, 2022:
Pediatric hematologist oncologist
https://twitter.com/acweyand/status/1535060704629235717

Infants exposed in utero to #COVID19 almost 2x more likely to have developmental disorders with greatest effect seen with 3rd trimester exposure.
--------------------------------------------------------------

Andrea G. Edlow et al. 2022. Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy. JAMA Netw Open. 9 June 2022;5(6):e2215787. doi:10.1001/jamanetworkopen.2022.15787 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793178

Key Points
Question Is COVID-19 exposure in utero associated with increased risk for neurodevelopmental disorders in the first year of life?

Findings In this cohort study of 7772 infants delivered during the COVID-19 pandemic, those born to the 222 mothers with a positive SARS-CoV-2 polymerase chain reaction test during pregnancy were more likely to receive a neurodevelopmental diagnosis in the first 12 months after delivery, even after accounting for preterm delivery.

Meaning These preliminary findings suggest that COVID-19 exposure may be associated with neurodevelopmental changes and highlight the need for prospective investigation of outcomes in children exposed to COVID-19 in utero.

Abstract
Importance Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring.

Objective To evaluate whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth.

Design, Setting, and Participants This retrospective cohort study examined live offspring of all mothers who delivered between March and September 2020 at any of 6 Massachusetts hospitals across 2 health systems. Statistical analysis was performed from October to December 2021.

Exposures Maternal SARS-CoV-2 infection confirmed by a polymerase chain reaction test during pregnancy.

Main Outcomes and Measures Neurodevelopmental disorders determined from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes over the first 12 months of life; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record.

Results The cohort included 7772 live births (7466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean (SD) maternal age of 32.9 (5.0) years; offspring were 9.9% Asian (772), 8.4% Black (656), and 69.0% White (5363); 15.1% (1134) were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers: 14.4% (32) vs 8.7% (654) .... Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses in unadjusted models (odds ratio (OR), 2.17 ...) as well as those adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR, 1.86 ...). Third-trimester infection was associated with effects of larger magnitude (adjusted OR, 2.34....

Conclusions and Relevance This cohort study of SARS-CoV-2 exposure in utero found preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring. Prospective studies with longer follow-up duration will be required to exclude confounding and confirm these associations.

...Table 2 (Frequency of Individual Developmental Disorder ICD-10-CM Codes in Cases and Controls) lists the most commonly observed neurodevelopmental diagnoses by case or control status, including
specific developmental disorder of motor function...,
expressive language disorder ..., and
developmental disorder of speech and language, unspecified ...

80margd
jun 11, 2022, 11:04 am

MICE: "While intramuscular vaccination prevented morbidity and cleared SARS-CoV-2 from the respiratory tract within several days after challenge, intranasal vaccination was more effective as neither infectious virus nor viral messenger (m)RNAs were detected in the nasal turbinates or lungs as early as 2 d after challenge, indicating prevention or rapid elimination of SARS-CoV-2 infection. Additionally, we determined that neutralizing antibody persisted for more than 6 mo and that serum induced to the Wuhan S protein neutralized pseudoviruses expressing the S proteins of variants, although with less potency, particularly for Beta and Omicron."

Eric Topol (Scripps) @EricTopol | 4:33 PM · Jun 9, 2022:
Enough with the mice. We need this for people

Performed better than intramuscular shots @PNASNews
Text highlighted ( https://twitter.com/EricTopol/status/1534997125930418177/photo/1 )
--------------------------------------------------------------

Jeffrey L. Americo et al. 2022. Intranasal inoculation of an MVA-based vaccine induces IgA and protects the respiratory tract of hACE2 mice from SARS-CoV-2 infection. PNAS June 9, 2022
119 (24) e2202069119 https://doi.org/10.1073/pnas.2202069119 https://pnas.org/doi/10.1073/pnas.2202069119

81margd
jun 12, 2022, 1:14 pm

"...two distinct patterns of potentially long COVID-19 liver manifestations in children (recovered from COVID-19 and later present(ing) with liver injury ) with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies..."

Cooper, Shiri et al. 2022. Long COVID-19 Liver Manifestation in Children (Rapid Communication). Pediatric Gastroenterology and Nutrition: June 10, 2022 - Volume - Issue - 10.1097/MPG.0000000000003521 doi: 10.1097/MPG.0000000000003521 https://journals.lww.com/jpgn/abstract/9900/long_covid_19_liver_manifestation_in...

Abstract
Objectives:
SARS CoV-2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury.

Methods:
This is a retrospective case-series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome.

Results:
We report five pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, two aged 8 years and one aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All three were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all five patients, extensive etiology workup for infectious and metabolic etiologies were negative.

Conclusions:
We report two distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.

82margd
jun 12, 2022, 2:43 pm

>81 margd: contd.

Dr Zoë Hyde @DrZoeHyde | 7:29 AM · Jun 12, 2022·
Epidemiologist & biostatistician. @RealOzSAGE scientific advisory group member.
https://twitter.com/DrZoeHyde/status/1535947425294483456

A study of the hepatitis cases seen in Israel reveals they were likely a delayed consequence of COVID-19.

The average delay was 74 days (range 21-130). This is almost certainly why we’ve mostly seen negative COVID-19 PCR tests in affected kids.

No adenovirus found in liver.🧵

The authors describe 5 children with hepatitis.

Four children previously had mild COVID-19, for which they tested positive by PCR at that time.

One child had a positive antibody test for SARS-CoV-2 during the hepatitis investigation, indicating previous asymptomatic COVID-19.

3-month-old infant: COVID-19 in Feb 2021, hospitalised with liver failure 21 days later.

5-month-old infant: liver failure in May 2021, antibody positive for COVID-19.

8-year-old boy: COVID-19 in Dec 2020, hospitalised for hepatitis 130 days later.

8-year-old boy: COVID-19 in Jan 2021, hospitalised for hepatitis 94 days later.

13-year-old boy: COVID-19 in Sep 2021, causing hepatitis that apparently resolved 39 days after COVID-19 diagnosis, then hospitalised for hepatitis again 53 days after COVID-19 diagnosis.

The authors looked for adenovirus, but didn’t find it in the children’s livers.

The authors write: “the adenovirus stain was negative in all, and the histologic features were not suggestive of adenovirus hepatitis.”

The authors go on to say: “three patients had adenovirus PCR performed from whole blood, and in one, it was positive. However, as the liver histology was not suggestive of adenovirus infection, we did not consider it as the culprit for the hepatitis.”

The authors think: “the mechanism of liver manifestation is either a post-infectious immune reaction similar to MIS-C, or an immune dysregulation causing priming to other infectious agent such as adenovirus by a prior infection with SARS-CoV-2”

Link to study: >81 margd:

83margd
jun 13, 2022, 5:51 am

>79 margd: Editorial on Edlow et al. (2022) below. :

Torri D. Metz. 2022. Is It Exposure to the Pandemic or to Maternal SARS-CoV-2 Infection That Is Adversely Affecting Early Childhood Neurodevelopment? JAMA Netw Open. 2022;5(6):e2215793. doi:10.1001/jamanetworkopen.2022.15793 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793181

Edlow and colleagues...associated exposure to SARS-CoV-2 in utero and neurodevelopmental disorders within the first 12 months of life...it was estimated to be approximately 3% in the unexposed group and 6% in the exposed group within the first 12 months.

...many questions remain. Essentially all of what we know now about the effects of in utero exposure to maternal SARS-CoV-2 infection is from children who were exposed to the early and Alpha variants of SARS-CoV-2 as those are the only children now old enough to undergo rigorous neurodevelopmental assessments. Knowledge about the effects of other variants is lacking. We know that the Delta variant substantially damaged the placenta4 and was associated with a much higher risk of stillbirth compared with other variants...

...we also have no data on whether prior vaccination will have a protective effect against adverse neurodevelopmental outcomes for the offspring of mothers with SARS-CoV-2 beyond the direct benefit of persistent antibodies in the cord blood and through infancy...

...these preliminary findings generate numerous additional research questions to explore.
Are there genetic predispositions to adverse outcomes?
Will we observe differential effects by SARS-CoV-2 variant, by severity of infection, and by trimester of infection?
Is it the virus itself or all of the societal changes that occurred during this period including differences in how those changes were experienced among those with and without SARS-CoV-2?

...how do we intervene to help mitigate the adverse effects of the pandemic on young children?...

84margd
jun 13, 2022, 7:59 am

EUA amendment request for Pfizer-BioNTech COVID-19 Vaccine
for use in children 6 months through 4 years of age
FDA Briefing Document (66p)
June 15, 2022 Vaccines and Related Biological Products Advisory Committee Meeting

Executive Summary is on p 5. NYT: "three doses of the Pfizer-BioNTech coronavirus vaccine appeared to be effective in preventing Covid illness in children under 5, judging by the level of virus-blocking antibodies the shots induced." https://www.nytimes.com/2022/06/12/us/politics/pfizer-covid-vaccine-under-5.html

https://www.fda.gov/media/159195/download

85margd
jun 20, 2022, 3:06 pm

Nigeria:

NowThis @nowthisnews | 1:03 PM · Jun 19, 2022:

‘If you start blaming Africans for not taking the vaccines, you’re just basically misunderstanding … what the situation is’ — Edwin Ikhuoria, Africa executive director at ONE, breaks down how a broken system fueled COVID-19 vaccine hesitancy across the continent

How COVID-19 Vaccine Hesitancy in Africa Is Linked to Lack of Access
Edwin Ikhuoria, Africa executive director at ONE, breaks down how a broken system fueled COVID-19 vaccine hesitancy across the continent
4:43 ( https://twitter.com/nowthisnews/status/1538568038722805760 )

86margd
jun 20, 2022, 4:17 pm

Abraar Karan @AbraarKaran | 7:50 PM · Jun 18, 2022:

Covid is both a clinical and public health problem
Clinically we have made incredible advances to reduce mortality— vaccines, antivirals, monoclonals, steroids etc
The same cannot be said on the public health front to prevent transmission
These are two different problems.

2/ These problems continue to be conflated, including by our government and public health leaders. Reducing mortality against the current variants that we are dealing with is not enough; we must reduce transmission such that we are protected against all future threats as well.

3/ Just finished reading this great interview from my friend @DhruvKhullar
in NewYorker w @ashishkjha

“We Have to Get Out of This Phase”: Ashish Jha on the Future of the Pandemic
President Biden’s COVID czar talks about his public-health philosophy, his Twitter threads, his unlikely path to the White House, and where we go from here.
Dhruv Khullar | June 18, 2022

...(Jha) ...In the future, we have to have enough vaccine-production capability around the world. So whenever we get a pathogen we can make so many doses so fast that this issue of who gets it first, who gets it second, becomes a non-issue. Before this pandemic, there wasn’t really a single good vaccine-manufacturing site on the continent of Africa. We’re beginning to make some changes there, but that needs to change faster. It’s also a reminder that it’s not just about having enough vaccines or therapeutics. It’s about figuring out how to help countries deploy them.

...We’re two years into this pandemic, and think about what science has already delivered: lots of effective treatments, multiple powerful vaccines that continue to prevent serious illness. In the coming years, we will have vaccines that are more durable, that prevent transmission, that need to be taken infrequently. We’re going to get more therapeutics. Our ability to manage this virus is going to get better and better. The real question in my mind is: What can we do to speed up that process? The hard part is turning all the great science into products that reach people in a timely and equitable way. That’s the job ahead.

https://www.newyorker.com/news/the-new-yorker-interview/we-have-to-get-out-of-th...

87margd
jun 22, 2022, 8:08 am

Darn...

Tara Moriarty (U Toronto) @MoriartyLab | 2:20 AM · Jun 21, 2022:
The 1st version of this study ended with Delta. This (Al-Aly 2022) includes Omicron. The dataset is massive and results are compelling. Each successive infection increases risk of death and serious complications, in unvaccinated AND vaccinated individuals. Avoid infection/reinfection. Now.
-------------------------------------------------------

A reinfection red flag
Why a new report is so troubling
Eric Topol | 21 June 2021

...comparison of people with reinfections vs those with only 1 infection.* Note the doubling of all-cause mortality, cardiovascular, and lung adverse outcomes, 3-fold risk of hospitalization, and impact on other health domains...

Next is the durability of these adverse outcomes for this same comparison (reinfections vs 1 infection) in 30-day increments, indicating that much of the hit was up front, but persistent increased risk was evident for most endpoints throughout the 6 months follow-up...

Finally, there is the “dose-response” effect of multiple reinfections. By that I mean with additional episodes of Covid, for every outcome there was a stepwise increased risk, both relative... and absolute ...

...reinfection was quite rare before the Omicron wave hit, at 1% or less through the Delta variant wave

The new Omicron subvariants portend much more reinfections...Today’s CDC update of genomics shows we have 35% of new cases accounted by the BA.4/5 variants, which have the most immune-evasiveness of any variant since the pandemic began, and 56% by BA.2.12.1....

...besides vulnerability to reinfections, the Omicron BA.1 specific vaccines, due to become available this Fall, may not provide enhanced protection as anticipated. BA.4/5 are too different from BA.1 with respect to how our immune system sees them.

What should we do about this?
...gear up with N95/KN95 masks,
distancing when possible,
attention to ventilation,
air filtration, and
all of the non-pharmacologic measures that we have at our disposal to limit infections and reinfections.

Booster shots can help, especially when more than 4 months have elapsed from primary vaccination or a third shot. Children of all ages will benefit from vaccination, including the new approval for age 5 years (& under), even if they have had Omicron infections with BA.1, owing to the narrow and often insufficient immune response that may not protect from BA.4/5 and subsequent variants.

Beyond that is my #1 frustration ...(Researchers:) go after pan-β-coronavirus and nasal vaccines with the same aggressive (OWS) template...

https://erictopol.substack.com/p/a-reinfection-red-flag
-------------------------------------------------------------

Ziyad Al-Aly et al. 2022. Outcomes of SARS-CoV-2 Reinfection.
Research Square: Versions 1, 17 June 2022. https://doi.org/10.21203/rs.3.rs-1749502/v1 https://www.researchsquare.com/article/rs-1749502/v1

Preprint. Not yet peer-reviewed.

ABSTRACT
First infection with SARS-CoV-2 is associated with increased risk of acute and post-acute death and sequelae in the pulmonary and extrapulmonary organ systems. However, whether reinfection adds to the risk incurred after the first infection is not clear. Here we use the national health care databases of the US Department of Veterans Affairs to build a cohort of people with first infection (n = 257,427), reinfection (2 or more infections, n = 38,926), and a non-infected control group (n = 5,396,855) to estimate risks and 6-month burdens of all-cause mortality, hospitalization, and a set of pre-specified incident outcomes. We show that compared to people with first infection, reinfection contributes additional risks of all-cause mortality, hospitalization, and adverse health outcomes in the pulmonary and several extrapulmonary organ systems (cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders); the risks were evident in those who were unvaccinated, had 1 shot, or 2 or more shots prior to the second infection; the risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and most were still evident at 6 months after reinfection. Compared to non-infected controls, assessment of the cumulative risks of repeated infection showed that the risk and burden increased in a graded fashion according to the number of infections. The constellation of findings show that reinfection adds non-trivial risks of all-cause mortality, hospitalization, and adverse health outcomes in the acute and post-acute phase of the reinfection. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.

88margd
jun 22, 2022, 9:01 am

>87 margd: a bit more encouraging...

Eric Topol @EricTopol | 7:00 AM · Jun 22, 2022
Some good news about the Omicron BA.1-specific (bivalent w/ ancestral) booster vaccine @moderna_tx today:

induced a 5.4-fold increase in neutralizing antibodies vs BA.4/5 (albeit 3-fold lower than vs. BA.1)

Why is this important?
erictopol.substack.com
A reinfection red flag
Why a new report is so troubling
-----------------------------------------------------------------

It will be a while before scientists SEE the data, much less review it... Already Twitter is noting no comparison with 4th shot, but a little encouraging news is always welcome!

Moderna Announces Omicron-Containing Bivalent Booster Candidate mRNA-1273.214 Demonstrates Superior Antibody Response Against Omicron
Moderna Investor Press Release June, 08, 2022

https://investors.modernatx.com/news/news-details/2022/Moderna-Announces-Omicron...

89margd
jun 23, 2022, 5:53 am

"Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination...Hospitalization rates among babies (six months and younger) were six times as high during the Omicron surge compared to the Delta peak."

Vaxx in pregnancy protects newborns thru 6 months. For Omicron, "Effectiveness was 69% ... when maternal vaccination occurred after 20 weeks of pregnancy and 38% ... during the first 20 weeks of pregnancy..." But delaying vaxx to 20wks, while better protecting newborns, leaves newly pregnant moms susceptible to severe COVID...

Newborns' Protection With Moms' COVID Vax Dips During Omicron
— Effectiveness against infant hospitalization declined from 80% during Delta to 38% in Omicron era
by Amanda D'Ambrosio, Enterprise & Investigative Writer, MedPage Today June 22, 2022

..."The finding that the risk of hospitalization, and in particular, hospitalization in an ICU, was reduced among infants whose mothers had been fully vaccinated during pregnancy provides evidence of additional benefits of maternal vaccination beyond those previously reported for the mother," Patel and colleagues stated.

But maternal vaccination was associated with lower protection against COVID-related infant hospitalization during the Omicron period (38%...) compared with when Delta was the predominant strain (80%...).

This "moderate" reduced risk of infant hospitalization during the Omicron period is still meaningful for an age group not likely to get access to a licensed vaccine in the foreseeable future, Patel's group noted.

COVID-19 had serious adverse outcomes for infants under 6 months, particularly during the Omicron wave. Hospitalization rates among babies in this age group were six times as high during the Omicron surge compared to the Delta peak. Additionally, COVID was the primary reason for hospitalization among 85% of babies in this age group...

...Compared to case infants whose mothers had not been fully vaccinated, those whose mothers were vaccinated had a lower incidence of ICU admission, critical COVID-19, mechanical ventilation, and vasoactive infusions...

https://www.medpagetoday.com/obgyn/pregnancy/99379
---------------------------------------------------------------------

Natasha B. Halasa et al. 2022. Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants. NEJM22 June 2022. DOI: 10.1056/NEJMoa2204399

Abstract
Background.
Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants...

Results
A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 (12%) received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant’s mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% ... overall, 80% ...during the delta period, and 38% ... during the omicron period. Effectiveness was 69% ... when maternal vaccination occurred after 20 weeks of pregnancy and 38% ... during the first 20 weeks of pregnancy...
------------------------------------------------------------------

Sonja A. Rasmussen and Denise J. Jamieson 2022. COVID-19 Vaccination during Pregnancy -- Two for the Price of One (Editorial). NEJM June 22, 2022. DOI: 10.1056/NEJMe2206730 https://www.nejm.org/doi/full/10.1056/NEJMe2206730

...The results of the study by Halasa et al. provide compelling evidence that maternal vaccination is effective in reducing the risk of Covid-19–related hospitalization in infants younger than 6 months of age, a finding that further supports recommendations for Covid-19 vaccination during pregnancy. Such infants have a higher risk of severe illness and hospitalization than older children and cannot be vaccinated now or in the near future. Because vaccines are less likely to be effective in infants younger than 6 months of age,1 the recently completed clinical trials of Covid-19 vaccines in young children have excluded that age group.

This study also raises the question of the appropriate timing of Covid-19 vaccination during pregnancy. Determining the appropriate timing is difficult because the benefits of maximizing infant protection must be balanced against the maternal risks of delaying vaccination, given the increased risk of severe Covid-19 during pregnancy. Further study is needed to assess whether an additional booster dose given in later pregnancy would increase infant protection...

90margd
jun 23, 2022, 6:04 am

Eric Topol @EricTopol | 10:42 PM · Jun 22, 2022:
New @NEJM
No wonder why Omicron subvariants BA.2.12.1 and BA.4/5 are causing a lot of infections and reinfections in people who've have been vaccinated or had BA.1 or BA.2 infections, respectively.
A few added mutations in the spike sequence (BA.4/5) are leading to even more immune evasiveness and a new Covid wave in many places around the world

Nicole P. Hachmann et al. 2022. Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5 (Correspondence). NEJM June 22, 2022 DOI: 10.1056/NEJMc2206576 http://nejm.org/doi/full/10.10

...These data show that the BA.2.12.1, BA.4, and BA.5 subvariants substantially escape neutralizing antibodies induced by both vaccination and infection. Moreover, neutralizing antibody titers against the BA.4 or BA.5 subvariant and (to a lesser extent) against the BA.2.12.1 subvariant were lower than titers against the BA.1 and BA.2 subvariants, which suggests that the SARS-CoV-2 omicron variant has continued to evolve with increasing neutralization escape. These findings provide immunologic context for the current surges caused by the BA.2.12.1, BA.4, and BA.5 subvariants in populations with high frequencies of vaccination and BA.1 or BA.2 infection.

Fig. 1. Omicron Subvariant Mutations and Neutralizing Antibody Responses.
( https://twitter.com/EricTopol/status/1539714845175476224/photo/1 )

91margd
Bewerkt: jun 25, 2022, 7:55 am

Zain Chagla (McMaster U) @zchagla | 7:13 PM · Jun 24, 2022:
Interesting data on myo/pericarditis in Ontario after mRNA vaccines
-- Highest in 18-24 year old males
-- Higher with moderna than pfizer
-- Risk is markedly reduced with longer dosing intervals
Graph ( https://twitter.com/zchagla/status/1540473165285056512/photo/1 )
Table ( https://twitter.com/zchagla/status/1540473165285056512/photo/2 )
-----------------------------------------------------------

Sarah A. Buchan et al. 2022. Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada. JAMA Netw Open. 24 June 2022;5(6):e2218505. Doi:10.1001/jamanetworkopen.2022.18505 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793551?resultClick...

Conclusions
Although myocarditis or pericarditis following receipt of mRNA vaccines is rare, the findings of this study suggest that modifying mRNA COVID-19 vaccination programs to incorporate age-based product considerations and longer interdose intervals may reduce the risk of these events. Confirmation of these findings and further exploration of the association of heterologous mRNA vaccine schedules and interdose intervals with the risk of myocarditis or pericarditis are needed.
--------------------------------------------------------------

Eric S. Weintraub et al. 2022. Myocarditis or Pericarditis Following mRNA COVID-19 Vaccination.
JAMA Netw Open. 24 June 2022;5(6):e2218512. doi:10.1001/jamanetworkopen.2022.18512 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793555

...reported rates of myocarditis or pericarditis were higher after vaccination with mRNA-1273 compared with BNT162b2 and that for both vaccines, the rate was higher following dose 2 of the primary 2-dose series when the interdose interval (the timing between dose 1 and dose 2) was 30 days or less.

...Reported rates of myocarditis or pericarditis were higher following dose 2

...reported rates for myocarditis and pericarditis among male individuals were higher than those among female individuals for all but 1 age group (25 to 39 years).

... lowest rates occurring among individuals with interdose intervals of 56 days or more

Another new contribution of the study by Buchan and colleagues is the finding that a heterologous second dose with mRNA-1273 (ie, BNT162b2 for dose 1 followed by mRNA-1273 for dose 2) was associated with higher reported rates of myocarditis or pericarditis than was a homologous second does with mRNA-1273 (ie, mRNA-1273 for both dose 1 and dose 2).

92margd
jun 25, 2022, 9:00 am

Eric Topol @EricTopol | 3:10 PM · Jun 23, 2022:
Just out @ScienceMagazine
"Our findings highlight the urgent need to find next-generation COVID-19 vaccines and broad-spectrum therapeutics, as well as to tighten non-pharmaceutical measures to reduce acute and chronic disease burden..."

Shuofeng Yuan et al. 2022. Pathogenicity, transmissibility, and fitness of SARS-CoV-2 Omicron in Syrian hamsters (Report). Science 23 Jun 2022. DOI: 10.1126/science.abn8939 https://www.science.org/doi/10.1126/science.abn8939

...In summary, the present study shows that despite comparatively lower pathogenicity than Delta, Omicron undoubtedly still causes obvious disease in infected hosts. Taking into consideration of Omicron’s high transmissibility, our findings highlight the urgent need to find next-generation COVID-19 vaccines and broad-spectrum therapeutics, as well as to tighten non-pharmaceutical measures to reduce acute and chronic disease burden (long COVID) on the public and healthcare facilities.

93margd
Bewerkt: jun 25, 2022, 9:30 am

Florian Krammer (Icahn Mt Sinai) @florian_krammer | 12:27 PM · Jun 23, 2022:
Important for the MS community:

Ilana Katz Sand...Florian Krammeret al. 2022. Evaluation of immunological responses to third COVID-19 vaccine among people treated with sphingosine receptor-1 modulators and anti-CD20 therapy. MedRxiv 14 June 2022. doi: https://doi.org/10.1101/2022.06.10.22276253 https://www.medrxiv.org/content/10.1101/2022.06.10.22276253v1

ABSTRACT
...Conclusions and Relevance: Participants on immunomodulators had impaired antibody neutralization capacity, particularly to BA.1, even after a third vaccine. T cell responses were not affected by anti-CD20 therapies*, but were nearly abrogated by S1PR modulators.** These results have clinical implications warranting further study.

...Discussion...Future directions include assessing durability of vaccine responses over time, studying the impact of natural infection with new variants, and most importantly, correlation with
clinical outcomes. For those on S1PR modulators, future studies could consider brief cessation of therapy to aim for an improved response to additional injection, weighing potential benefits and risks of such a strategy.

* B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity. (Wikipedia). The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several autoimmune diseases. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688039/

** Sphingosine-1-phosphate receptor modulators are a class of drugs used as immunomodulators, most notably in cases of multiple sclerosis. These drugs have the ability to modulate the G-protein coupled S1P receptors. Wikipedia

94margd
jun 25, 2022, 11:36 am

>88 margd: contd.

Eric Topol @EricTopol | 10:34 AM · Jun 25, 2022:
Important to note that both Moderna and Pfizer/BioNTech Omicron (BA-1) booster shots had 3-fold lower neutralizing antibody response to BA.4/5 than to BA.1
(Pfizer data just put out this morning)
Text ( https://twitter.com/EricTopol/status/1540704984081174530/photo/1 )

95margd
jun 25, 2022, 1:22 pm

Dr. Tom Frieden @DrTomFrieden | 1:10 PM · Jun 25, 2022:
Frmr CDC director

Almost 20 million more people globally are alive today because they got vaccinated against Covid, according to a new study—in just the first year vaccines were available!

Covid has been a formidable threat, but vaccines have saved an astounding number of lives and could have saved even more lives had access been more equitable globally and vaccination programs more able to reach all.
------------------------------------------------------------------

COVID-19 Cumulative Infection Collaborators. 2022. Estimating global, regional, and national daily and cumulative infections with SARS-CoV-2 through Nov 14, 2021: a statistical analysis. The Lancet Volume 399, ISSUE 10344, P2351-2380, June 25, 2022. DOI:https://doi.org/10.1016/S0140-6736(22)00484-6 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00484-6/fullt...

SUMMARY
...Findings
Global daily SARS-CoV-2 infections fluctuated between 3 million and 17 million new infections per day between April, 2020, and October, 2021, peaking in mid-April, 2021, primarily as a result of surges in India. Between the start of the pandemic and Nov 14, 2021, there were an estimated 3·80 billion (95% uncertainty interval 3·44–4·08) total SARS-CoV-2 infections and reinfections combined, and an estimated 3·39 billion (3·08–3·63) individuals, or 43·9% (39·9–46·9) of the global population, had been infected one or more times. 1·34 billion (1·20–1·49) of these infections occurred in south Asia, the highest among the seven super-regions, although the sub-Saharan Africa super-region had the highest infection rate (79·3 per 100 population ...). The high-income super-region had the fewest infections (239 million ...), and southeast Asia, east Asia, and Oceania had the lowest infection rate (13·0 per 100 population ...). The cumulative proportion of the population ever infected varied greatly between countries and territories, with rates higher than 70% in 40 countries and lower than 20% in 39 countries. There was no discernible relationship between R(effective) and total immunity, and even at total immunity levels of 80%, we observed no indication of an abrupt drop in R(effective), indicating that there is not a clear herd immunity threshold observed in the data.

Interpretation
COVID-19 has already had a staggering impact on the world up to the beginning of the omicron (B.1.1.529) wave, with over 40% of the global population infected at least once by Nov 14, 2021. The vast differences in cumulative proportion of the population infected across locations could help policy makers identify the transmission-prevention strategies that have been most effective, as well as the populations at greatest risk for future infection. This information might also be useful for targeted transmission-prevention interventions, including vaccine prioritisation. Our statistical approach to estimating SARS-CoV-2 infection allows estimates to be updated and disseminated rapidly on the basis of newly available data, which has and will be crucially important for timely COVID-19 research, science, and policy responses.

96margd
jun 27, 2022, 7:49 am

Eric Topol (Scripps) @EricTopol | 10:41 AM · Jun 26, 2022:
...simple graph...from @TheEconomist...saving ~20 million lives in the first year of Covid vaccinations

https://twitter.com/EricTopol/status/1541069239607361538/photo/1

https://economist.com/graphic-detail/2022/06/24/how-many-lives-have-been-saved-b...

97margd
jun 27, 2022, 8:45 am

John Burn-Murdoch (Financial Times) @jburnmurdoch | 12:35 PM · Jun 26, 2022:
NEW: unfortunately it’s time for another international Covid update, as the BA.5 Omicron lineage (and BA.4 to a lesser extent) sends not only cases but also hospitalisations climbing around the world, from South Africa, to Portugal, the UK, Israel and now the US

Graphs-hospitalisations by country
https://twitter.com/jburnmurdoch/status/1541097827954311168/photo/1

98margd
Bewerkt: jun 27, 2022, 9:05 am

Dr Satoshi Akima FRACP 『秋間聰』@ToshiAkima:
Nephrology & Internal Medicine. Immunothrombosis incl DIC. ISTH Member.

People who tested COVID positive had a
3.5 times increased risk of being diagnosed with Alzheimer's disease,
2.6 times with Parkinson's disease,
2.7 times with ischaemic stroke and a
4.8 times increased with intracerebral haemorrhage.

COVID-19 positive patients at higher risk of developing neurodegenerative disorders, new study shows
The European Academy of Neurology | June 24, 2022

...study presented today at the 8th European Academy of Neurology (EAN) Congress..., which analyzed the health records of over half of the Danish population, found that those who had tested positive for COVID-19 were at an increased risk of Alzheimer's disease, Parkinson's disease, and ischemic stroke.

...The increased risk of most neurological diseases was, however, no higher in COVID-19 positive patients than in people who had been diagnosed with influenza or other respiratory illnesses. COVID-19 patients did have a 1.7 times increased risk of ischaemic stroke in comparison to influenza and bacterial pneumonia inpatients over 80 years of age.

The frequency of other neurodegenerative illnesses such as multiple sclerosis, myasthenia gravis, Guillain-Barré syndrome and narcolepsy did not increase after COVID-19, influenza, or pneumonia...

More information: Frequency of neurological diseases after COVID-19, influenza A/B and bacterial pneumonia, presented at the EAN Congress 2022. (margd: no preprint or publication yet, apparently.)

https://medicalxpress.com/news/2022-06-covid-positive-patients-higher-neurodegen...

99margd
jun 27, 2022, 9:50 am

WHO African Region @WHOAFRO | 5:24 AM · Jun 26, 2022
#Africa 🌍 has received around 824M #COVID19 vaccines,
with more than 60% of these doses delivered via #COVAX while
~ 33% procured by countries through bilateral deals and donations 💉

100margd
jun 27, 2022, 10:22 am

Science Magazine @ScienceMagazine | 4:40 PM · Jun 25, 2022:
A new @ScienceTM study investigating the mysterious causes of #LongCOVID reports that the #SARSCoV2 virus can provoke persistent inflammation in the nervous system and olfactory tissues in hamsters and patient samples.

Justin J. Frere et al. 2022. SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations post recovery. Science Translational Medicine 7 Jun 2022. First Release. DOI: 10.1126/scitranslmed.abq3059 https://fcld.ly/t2ob5l2 https://www.science.org/doi/10.1126/scitranslmed.abq3059

Abstract
The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely impacted the olfactory bulb (OB) and epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month post viral clearance. These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

101margd
jun 27, 2022, 10:33 am

>88 margd: contd.

Spyros Chalkias et al. 2022. A Bivalent Omicron-containing Booster Vaccine Against Covid-19. MedRxiv 19 June, 2022. doi: https://doi.org/10.1101/2022.06.24.22276703 https://www.medrxiv.org/content/10.1101/2022.06.24.22276703v1

This article is a preprint and has not been certified by peer review

Abstract
Background Updated vaccination strategies against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern are needed. Interim results of the safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster candidate are presented.

Methods In this ongoing, phase 2/3 trial, the 50-μg bivalent vaccine mRNA-1273.214 (25-μg each ancestral Wuhan-Hu-1 and omicron B.1.1.529 spike SARS-CoV-2 mRNAs) was compared to the authorized 50-μg mRNA-1273 booster in adults who previously received 2-dose primary series of 100-μg mRNA-1273 and a first booster dose of 50-μg mRNA-1273 at least 3 months prior. Primary objectives were safety and reactogenicity, and immunogenicity of 50-μg mRNA-1273.214 compared with 50-μg mRNA-1273. Immunogenicity data 28 days after the booster dose are presented.

Results Four hundred thirty-seven and 377 participants received 50-μg of mRNA-1273.214, or mRNA-1273, respectively. Median time between first and second booster doses of mRNA-1273.214 and mRNA-1273 were similar (136 and 134 days, respectively). In participants with no prior SARS-CoV-2 infection, observed omicron neutralizing antibody geometric mean titers (GMTs ...) after the mRNA-1273.214 and mRNA-1273 booster doses, were 2372.4 ... and 1473.5 ... respectively and the model-based GMT ratio ... was 1.75 ... All pre-specified non-inferiority (ancestral SARS-CoV-2 with D614G mutation (D614G) GMT ratio; ancestral SARS-CoV-2 (D614G) and omicron seroresponse rates difference) and superiority primary objectives (omicron GMT ratio) for mRNA-1273.214 compared to mRNA-1273 were met. Additionally, mRNA-1273.214 50-μg induced a potent neutralizing antibody response against omicron subvariants BA.4/BA.5 and higher binding antibody responses against alpha, beta, gamma, delta and omicron variants. Safety and reactogenicity profiles were similar and well-tolerated for both vaccines groups.

Conclusion The bivalent vaccine mRNA-1273.214 50-μg was well-tolerated and elicited a superior neutralizing antibody response against omicron, compared to mRNA-1273 50-μg, and a non-inferior neutralizing antibody response against the ancestral SARS-CoV-2 (D614G), 28 days after immunization, creating a new tool as we respond to emerging SARS-CoV-2 variants.

102margd
jul 1, 2022, 8:59 am

Jerome Adams (frmr Surgeon General) @JeromeAdamsMD | 3:29 PM · Jun 29, 2022:

In a briefing to congress Tuesday FL Surgeon General Joseph Ladapo confirmed the decision to block county health departments from obtaining the COVID-19 vaccines for young children may prevent an estimated 30,000 disadvantaged kids from accessing vaccines.

miamiherald.com

103aspirit
jul 1, 2022, 10:06 am

>102 margd: and reminder: Florida is one of the states that refused to expand Medicaid using federal funds (90% of the costs). Many of the parents and guardians of the young kids whose healthcare is primarily through county health departments likely aren't covered when they themselves are sick-- for example, when their toddler shares the coronavrius picked up outside the home.

104margd
jul 1, 2022, 10:51 am

>103 aspirit: DeSanitize FL--but don't send him to DC, pls!
_________________________________________

COVID-19 may cause severe bone loss in arms, legs and spine
John Elder | June 26, 2022

...Researchers in the Department of Orthopaedic Surgery (Indiana University School of Medicine) discovered that mouse models infected with the coronavirus lost about 25 per cent of their bone mass within two weeks of becoming infected.

They also found mouse models suffered a 63 per cent increase in osteoclasts, the cells that cause bone to break down and be reabsorbed.

These changes “were observed even in mice with mild and asymptomatic infections”...

https://thenewdaily.com.au/life/wellbeing/2022/06/26/bone-loss-covid-19/
----------------------------------------------------------

Olatundun D.Awosanyaa et al. 2022. Osteoclast-mediated bone loss observed in a COVID-19 mouse model. Bone Volume 154, January 2022, 116227. https://doi.org/10.1016/j.bone.2021.116227
https://www.sciencedirect.com/science/article/pii/S8756328221003938

Highlights
• Mice surviving SARS-CoV-2 infection exhibit bone loss 12–14 days post-infection.
• Mice surviving SARS-CoV-2 infection exhibit increases in TRAP+ osteoclasts.
• Bone loss and elevated osteoclasts are seen in mice with no clinical signs of illness.

Abstract
The consequences of SARS-CoV-2 infection on the musculoskeletal system represent a dangerous knowledge gap. Aging patients are at added risk for SARS-CoV-2 infection; therefore, a greater understanding of the resulting musculoskeletal sequelae of SARS-CoV-2 infection may help guide clinical strategies. This study examined fundamental bone parameters among mice treated with escalating viral loads. ...While more studies are needed to investigate the long-term consequences of SARS-CoV-2 infection on skeletal health, this study demonstrates a significant reduction in several bone parameters and corresponding robust increases in osteoclast (responsible for aged bone resorption) number observed within 2 weeks post-infection in surviving asymptomatic and moderately affected mice.

105margd
jul 1, 2022, 11:07 am

Antonio Caramia @Antonio_Caramia | 3:39 AM · Jul 1, 2022:
Ingegnere gestionale, Consulente di direzione, ICT Manager, Responsabile Organizzazione e Sistemi Informativi

Just to say...
For 35 days in a row China recorded
0⃣ ZERO #COVID19 deaths ‼️
👉They test people every 48-72 hours!

Graph confirmed cases (https://twitter.com/Antonio_Caramia/status/1542774957306007553/photo/1 )
Chris Turnbull and 4 others

106margd
jul 1, 2022, 5:21 pm

The BA.5 story
The takeover by this Omicron sub-variant is not pretty
Eric Topol | Jun 27, 2022

The Biology of BA.5
Current status around the world

The ways we can defend against it
Obviously, the non-pharmacologic mitigating measures that include high-quality make (N95/KN95), physical distancing, ventilation and air filtration would help, but pandemic fatigue has led to very low level of adoption. Boosters would help, and it is noteworthy that for people age 50+ there is a substantial (14-fold) reduction for mortality as recently documented by the CDC for a 4th shot (previously published by the Israel investigators in multiple observational studies). That is 99% reduction in mortality for 4-shots vs 86% for 3 shots. But only 1 in 4 Americans age 50+ have had a fourth shot!...

https://erictopol.substack.com/p/the-ba5-story

107margd
jul 3, 2022, 12:14 pm

"similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID."

Anthony Fernández-Castañeda...Akiko Iwasaki... 2022. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. CELL June 12, 2022. DOI:https://doi.org/10.1016/j.cell.2022.06.008 https://www.cell.com/cell/fulltext/S0092-8674(22)00713-9#.YsGSXg1ire4.twitter

Highlights
• Respiratory COVID induces CSF cytokine elevation and microglial reactivity
• CCL11 activates hippocampal microglia and impairs neurogenesis
• Respiratory COVID causes persistent loss of oligodendrocytes and myelinated axons
• Respiratory influenza causes similar but less persistent cellular dysregulation

Summary
COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

Graphical abstract (See online.)

108margd
jul 3, 2022, 1:21 pm

Dr Greg Kelly @drgregkelly | 10:24 AM · Jul 2, 2022
Pediatrician / ICU specialist / BMedSc inf disease / MBA. How stuff works &how it fails. Affiliations @pedsintensiva @UQMedicine (Queensland U) @realOzSAGE

This* should be a proper “oops” moment in our #COVID19 response, and quite possibly an “oh shit” one
Here is real world data confirming earlier predictions that the time between covid waves would progressively decrease
Why is this so concerning?
🧵 https://twitter.com/drgregkelly/status/1543239238107660290

...“Oh shit” moment is this:
#COVID19 rampant for 2.5 years & shot off countless evolutionary branches in myriad directions
More & more variants that less & less relate to ones we have protection against due to prev infections, vax or antivirals
Each wave worsens as more mutation...
-----------------------------------------------------------------
* Quote Tweet
Diego Bassani, PhD @DGBassani | 5:59 PM · Jul 1, 2022
🇨🇦 Senior Scientist/Epidemiologist @SickKidsNews @SickKidsGlobal
Assoc. Prof @UofTMedicine @UofT_DLSPH. 🇧🇷 Alumnus @ufrgsnoticias @UFPel

Nicer plots of the terrible situation we've put ourselves into.
First a bird's eye view of how the frequency of substitution is increasing in Canada.
This is empirical data showing variant substitution. It was a drawing back in April, see quoted tweet.
https://twitter.com/DGBassani/status/1512896331878121473?s=20&t=cCdoMfZM6TeY...
Graph variant substitution Canada 2020-2022 ( https://twitter.com/DGBassani/status/1542991378073935877/photo/1 )

109margd
jul 3, 2022, 1:48 pm

>107 margd: Yay?

Eric Topol @EricTopol | 7:28 PM · Jul 2, 2022:
Small study of health care workers suggests possibility that there may be increased protection from #LongCovid with increased doses of vaccine https://ja.ma/3ul2jCZ ⁦@JAMANetworkOpen

Table 2--association of patient characteristics and lond COVID
https://twitter.com/EricTopol/status/1543376082337820674/photo/1

110margd
jul 3, 2022, 4:21 pm

:)

Benjamin Mazer @BenMazer | 1:06 PM · Jul 3, 2022:
Surgical pathologist specializing in diseases of the gastrointestinal tract and liver. Also a writer on the evidence-based medicine beat.

Many people seem to have missed that the Kaiser/Pfizer folks updated their Lancet Resp Med paper that purported to show waning of the third vaccine dose against severe disease with further data showing NO MAJOR WANING in immunocompetent recipients.

Sara Y Tartof et al. 2022. Immunocompromise and durability of BNT162b2 vaccine against severe outcomes due to omicron and delta variants (Correspondence). The Lancet: Volume 10, ISSUE 7, e61-e62, July 01, 2022. DOI:https://doi.org/10.1016/S2213-2600(22)00170-9 https://thelancet.com/journals/lanres/article/PIIS2213-2600(22)00170-9/fulltext

111margd
Bewerkt: jul 8, 2022, 7:46 am

Linsey Marr @linseymarr | 10:53 AM · Jul 7, 2022:
Engineering professor @virginia_tech with expertise in airborne transmission of viruses, air quality, nanotechnology.
(Discussion at https://twitter.com/linseymarr/status/1545058494449012743)

Preprint on ventilation intervention in schools in Italy now at https://arxiv.org/abs/2207.02678. Relative risk of infection⬇️ with⬆️in ventilation: 10-14 L/s per person reduced likelihood of infection 80% compared to natural ventilation only.
----------------------------------------------

Luca Ricolfi et al. 2022. Increasing ventilation reduces SARS-CoV-2 airborne transmission in schools: a retrospective cohort study in Italy's Marche region. Cornell U, arxiv. Submitted on 5 Jul 2022. https://arxiv.org/abs/2207.02678

Preprint. Not yet peer-reviewed.

Background: While increasing the ventilation rate is an important measure to remove inhalable virus-laden respiratory particles and lower the risk of infection, direct validation in schools with population-based studies is far from definitive.

Methods: We investigated the strength of association between ventilation and SARS-CoV-2 transmission reported among the students of Italy's Marche region in more than 10,000 classrooms, of which 316 were equipped with mechanical ventilation. We used ordinary and logistic regression models to explore the relative risk associated with the exposure of students in classrooms.

Findings: For classrooms equipped with mechanical ventilation systems, the relative risk of infection decreased with the increase in ventilation: ventilation ranging from 10 to 14 L s-1 student-1 reduced the likelihood of infection for students by 80% compared with a classroom with only natural ventilation. From the regression analysis, as confirmed by the predictive theoretical approach, we obtained a relative risk reduction in the range 12%-15% for each additional unit of ventilation rate per person.

Interpretation: We need high ventilation rates (more than 10 L s−1 student−1) to protect students in classrooms from airborne transmission; this is higher than the rate needed to ensure indoor air quality. The excellent agreement between the results from the retrospective cohort study and the outcomes of the predictive theoretical approach makes it possible to assess the risk of airborne transmission for any indoor environment.

112margd
jul 8, 2022, 8:01 am

The most transmissible coronavirus subvariant yet, BA.5, is threatening a new wave of infections in the U.S., even among those who recovered from the virus fairly recently. The risk from Covid is increasing in much of the country, according to the CDC.

What the BA.5 Subvariant Could Mean for the United States
Lauren Leatherby | July 7, 2022
https://www.nytimes.com/interactive/2022/07/07/us/ba5-covid-omicron-subvariant.h...

113margd
jul 8, 2022, 8:38 am

"brass instruments, on average, producing 191% ... more aerosol (emissions) than woodwinds"

John Volckens et al. 2022. Aerosol emissions from wind instruments: effects of performer age, sex, sound pressure level, and bell covers. Nature, Scientific Reports volume 12, Article number: 11303 (4 July 2022)

Abstract
Aerosol emissions from wind instruments are a suspected route of transmission for airborne infectious diseases, such as SARS-CoV-2. We evaluated aerosol number emissions (from 0.25 to 35.15 μm) from 81 volunteer performers of both sexes and varied age (12 to 63 years) while playing wind instruments (bassoon, clarinet, flute, French horn, oboe, piccolo, saxophone, trombone, trumpet, and tuba) or singing. Measured emissions spanned more than two orders of magnitude, ranging in rate from less than 8 to 1,815 particles s−1, with brass instruments, on average, producing 191% ... more aerosol than woodwinds. Being male was associated with a 70% increase in emissions (vs. female...). Each 1 dBA increase in sound pressure level was associated with a 28% increase ... in emissions from brass instruments; sound pressure level was not associated with woodwind emissions. Age was not a significant predictor of emissions. The use of bell covers reduced aerosol emissions from three brass instruments tested (trombone, tuba, and trumpet), with average reductions ranging from 53 to 73%, but not for the two woodwind instruments tested (oboe and clarinet). Results from this work can facilitate infectious disease risk management for the performing arts.

114margd
jul 8, 2022, 9:03 am

Edward Nirenberg 🇺🇦 @ENirenberg
Today on really cool vaccine things, I want to talk about this paper:
https://sciencedirect.com/science/article/pii/S2666379122002294 *

IMO it's a paper you should be very excited about because it offers a proof of concept for next-generation vaccines that could elicit robust mucosal immunity.proof of concept for next-generation vaccines (prevent infection, not just serious disease)...
--------------------------------------------------------------

Ebony N.Gary et al. 2022. Parenteral mucosal chemokine adjuvant enhances synDNA vaccine-mediated peripheral and mucosal responses to SARS-CoV-2 and provides heterologous protection in vivo. Cell Reports Medicine. Journal Pre-proof available online 28 June 2022. https://doi.org/10.1016/j.xcrm.2022.100693 https://www.sciencedirect.com/science/article/pii/S2666379122002294

Highlights
• Mucosal chemokine CCL27 (CTACK) enhances SARS-CoV-2 DNA vaccine-induced responses.
• CTACK co-delivery supports 100% protection SARS-CoV-2 VOC challenge.
• Enhanced mucosal immunity may support broad protection from SARS-CoV-2 variants.

Graphical Abstract ( https://twitter.com/ENirenberg/status/1545101551085277187/photo/1 )

115margd
jul 8, 2022, 9:37 am

Bob Wachter @Bob_Wachter | 10:15 PM · Jul 3, 2022:
Chair, UCSF Dept of Medicine.
https://twitter.com/Bob_Wachter/status/1543780629015236608

...It seems clear that BA.5 will lead to an ongoing plateau, if not a moderate surge, lasting through summer & into fall. Beyond that, much depends on whether a new variant emerges to supplant it. Given the pattern of the past year, it would be foolish to bet against that.(24/25)

I wish I had a happier analysis of our current Covid state. But BA.5 is yet another Covid curveball to be dealt with, and it's not great news.
(And I wish that BA.5 was the only bad news in the U.S. these days.)
Despite all of it, I hope you have a happy & healthy 4th! (25/end)

116margd
jul 8, 2022, 9:53 am

A handful of emergency departments are cutting hours and even closing in Ontario...

Tara Moriarty @MoriartyLab _| 9:24 AM · Jul 6, 2022:
Assoc Prof @UofTDentistry @UofTMedicine. Bloodborne infections, Lyme disease, misinformation.
In Quebec, 6,700 healthcare workers are now out sick with COVID, 1,000 more than last week, and nearly double COVID absences a month ago.

Alain Vadeboncoeur @Vadeboncoeur_Al · Jul 6
"Au début du mois de juin, la province enregistrait 3670 absences liées à la COVID-19 chez les travailleurs de la santé, environ la moitié de ce qui est recensé actuellement." Le réseau de la santé durement touché https://lapresse.ca/covid-19/2022-07-06/hausse-des-cas-de-covid-19/le-reseau-de-...
via @lp_lapresse

117margd
jul 8, 2022, 10:47 am

U.S. pharmacists receive permission from the F.D.A. to prescribe Pfizer’s Covid pills.
Rebecca Robbins | July 6, 2022

...the F.D.A. said that Covid patients seeking a prescription for (Paxlovid) pills from a pharmacist should bring records of their recent blood tests and a list of the other medications they take. The pharmacist should then review the records for potential kidney or liver problems or problematic interactions between Paxlovid and the patient’s other drugs, the agency said. A component of Pfizer’s treatment can interfere with certain medications, including common ones for cholesterol and cardiovascular issues, potentially causing serious side effects.

The agency said that pharmacists should refer patients to other prescribers if the records and information about other medications was not available...

https://www.nytimes.com/2022/07/06/business/fda-paxlovid-prescriptions-pharmacie...

118margd
Bewerkt: jul 8, 2022, 11:55 am

Here’s what we know about COVID-19’s impact on the brain (7:37)
Apr 15, 2022

When COVID-19 first emerged, many researchers were focused on its impact on the lungs. But others, including Avindra Nath, Clinical Director of the National Institute of Neurological Disorders and Stroke, suspected COVID could also have a profound impact on the brain. Brain autopsy data from those who have died of COVID-19 have confirmed these early suspicions, revealing damaged blood vessels and inflammatory cells. Less is known about the direct impact on the brains of people with persisting symptoms weeks after an initial infection, a condition known as Long COVID. What at first seemed like a laundry list of neurological symptoms has now been focused into major categories, says Serena Spudich, a neurologist at Yale University. Watch to learn how researchers and doctors have been teasing apart how COVID impacts the brain, and testing treatments to alleviate symptoms.

https://www.youtube.com/watch?v=7RjItCm_YpU
________________________________________

Myoung Hwa Lee et al. 2022. Neurovascular injury with complement activation and inflammation in COVID-19. Brain, awac151, 15 July 2022. https://doi.org/10.1093/brain/awac151

Abstract
The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms.

In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry.

All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed.

All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia.

Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.

119margd
jul 8, 2022, 12:56 pm

Florian Krammer @florian_krammer | 8:33 AM · Jul 5, 2022:
Nice preprint by @DorotheeLaer and her colleagues in Innsbruck about mutations that confer resistance to paxlovid.

Quote Tweet
Björn Meyer @_b_meyer | 1:57 AM · Jul 5, 2022:
SARS-CoV-2 3CLpro mutations confer resistance to Paxlovid (nirmatrelvir/ritonavir) in a VSV-based, non-gain-of-function system https://biorxiv.org/content/10.1101/2022.07.02.495455v1
Show this thread ( https://twitter.com/_b_meyer/status/1544198864261062670 )
--------------------------------------------------------------

Emmanuel Heilmann etal. 2022. SARS-CoV-2 3CLpro mutations confer resistance to Paxlovid (nirmatrelvir/ritonavir) in a VSV-based, non-gain-of-function system. BioRxiv 4 July 2022.
doi: https://doi.org/10.1101/2022.07.02.495455

This article is a preprint and has not been certified by peer review

One-Sentence Summary
Mutations of the main protease of SARS-CoV-2 result in resistance against licensed drugs such as Paxlovid (nirmatrelvir / ritonavir).

120margd
jul 8, 2022, 1:11 pm

Scott Gottlieb, MD (frmr FDA commisioner)@ScottGottliebMD | 1:13 AM · Jul 5, 2022:
Elegant scientific work providing more support for view that chronic SARS-CoV-2 infection of immunocompromised individuals could lead to the emergence of genetically divergent lineages. Has implications for how we should identify and address chronic infection in such individuals.

Quote Tweet
Chrispin Chaguza @ChrispinChaguza · Jul 3
https://twitter.com/ChrispinChaguza/status/1543730086658056192

🧵for our latest preprint on the intrahost evolution of SARS-CoV-2 virus in an immunocompromised individual (60s) with a history of cancer chronically infected for at least 471 days (ongoing) with consistently replicating viruses at a high viral load. 1/n...

Chrispin Chaguza et al. 2022. Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection. MedRxiv 2 July 2022 doi: https://doi.org/10.1101/2022.06.29.22276868 https://medrxiv.org/content/10.1101/2022.06.29.22276868v1

This article is a preprint and has not been peer-reviewed

Summary
The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral loads. During the infection, we found an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution led to the emergence and persistence of at least three genetically distinct genotypes suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, using unique molecular indexes for accurate intrahost viral sequencing, we tracked the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, ultimately providing opportunity for the emergence of genetically divergent and potentially highly transmissible variants as seen with Delta and Omicron.

121margd
Bewerkt: jul 10, 2022, 9:18 am

Researchers found a 5-fold increase in risk of deep vein thrombosis, a 33-fold increase in risk of pulmonary embolism, and an almost twofold increase in risk of bleeding in the 30 days after infection. Risks were highest in patients with more severe covid-19 and during the first pandemic wave compared with the second and third waves, which the researchers say could be explained by improvements in treatment and vaccine coverage in older patients after the first wave.

Roland Baker 2.0 RolandBakerIII | 2:06 PM · Jul 9, 2022:
Molecular Genetics, U.C. Berkeley Alumnus Private sector
https://twitter.com/RolandBakerIII/status/1545831688260882433

(1/n) BMJ: Study finds risk of serious blood clots up to six months after covid-19: A study from Sweden published by The BMJ today finds an increased risk of deep vein thrombosis (a blood clot in the leg) up to three months after covid-19 infection...

(2/n) pulmonary embolism (a blood clot in the lung) up to six months, and a bleeding event up to two months. The findings also show a higher risk of events in patients with underlying conditions (comorbidities), patients with more severe covid-19, and during the first pandemic

(3/n) wave compared with the second and third waves. The researchers say these results support measures to prevent thrombotic events (thromboprophylaxis), especially for high risk patients, and strengthen the importance of vaccination against covid-19.

(4/n) Using national registries in Sweden, they identified more than 1 million people with confirmed SARSCoV-2 infection between 1 February 2020 - 25 May 2021, matched by age, sex & county of residence to more than 4 million people who had not had a positive SARS-CoV-2 test result.

(7/n) The results show that compared with the control period, risks were significantly increased 90 days after covid-19 for deep vein thrombosis, 180 days for pulmonary embolism, and 60 days for bleeding.

(8/n) After taking account of a range of potentially influential factors, the researchers found a 5-fold increase in risk of deep vein thrombosis, a 33-fold increase in risk of pulmonary embolism, and an almost twofold increase in risk of bleeding in the 30 days after infection.

(9/n) In absolute terms, this means that a first deep vein thrombosis occurred in 401 patients with covid-19 (absolute risk 0.04%) and 267 control patients (absolute risk 0.01%).

(10/n) A first pulmonary embolism event occurred in 1,761 patients with covid-19 (absolute risk 0.17%) and 171 control (absolute risk 0.004%), and a first bleeding event occurred in 1,002 patients with covid-19 (absolute risk 0.10%) and 1,292 controls (absolute risk 0.04%).

(11/n) Risks were highest in patients with more severe covid-19 and during the first pandemic wave compared with the second and third waves, which the researchers say could be explained by improvements in treatment and vaccine coverage in older patients after the first wave.

“Our findings arguably support thromboprophylaxis to avoid thrombotic events, especially for high risk patients, and strengthen the importance of vaccination against covid-19,” they conclude.

A 33-fold increase in risk of pulmonary embolism.
Is that a lot?...
--------------------------------------------------------

Ioannis Katsoularis et al. 2022. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ 06 April 2022; 377:e069590 doi: https://doi.org/10.1136/bmj-2021-069590 https://bmj.com/company/newsroom/study-finds-increased-risk-of-serious-blood-clo...
---------------------------------------------------------

Methods of DVT prophylaxis include general measures: the use of aspirin, mechanical prevention with graduated compression stockings, and intermittent pneumatic compression devices.

Preventing deep vein thrombosis in hospital inpatients - PMC - NCBI
https://www.ncbi.nlm.nih.gov › articles › PMC1925160
----------------------------------------------------------

Preventing DVT
Get up and walk around every 1 to 2 hours.
Exercise your legs while you're sitting by: Raising and lowering your heels while keeping your toes on the floor. Raising and lowering your toes while keeping your heels on the floor. Tightening and releasing your leg muscles.
Wear loose-fitting clothes.

What is Venous Thromboembolism? | CDC
https://www.cdc.gov › ncbddd › dvt › facts

122margd
Bewerkt: jul 12, 2022, 10:51 am

2 to 3 doses of vaccine ⬇️ #LongCOVID by 75% to 85%

WesElyMD @WesElyMD | 6:53 PM Jul 11, 2022
ICU Doctor @ Vanderbilt & VA. Our @CIBScenter studies COVID19 & Long Covid, Delirium, Dementia, PTSD, ICU Recovery, & End-of-Life.

COVID Vaccine reduces Long COVID

JAMA data in 2.5k people shows (vs 0 vaccine doses & adjusting for pt differences) 2 to 3 doses of vaccine ⬇️ #LongCOVID by 75% to 85% 👊

B5 #Omicron is SUPER contagious & lessening LC risk is a great incentive to #Vaxx

Table ( https://twitter.com/WesElyMD/status/1546628748950343682/photo/1 )
Highlighted text ( https://twitter.com/WesElyMD/status/1546628748950343682/photo/2 )
Highlighted text ( https://twitter.com/WesElyMD/status/1546628748950343682/photo/3 )

------------------------------------------------

Elena Azzolini et al. 2022. Association Between BNT162b2 Vaccination and Long COVID After Infections Not Requiring Hospitalization in Health Care Workers (Research Letter). JAMA. Published online July 1, 2022. doi:10.1001/jama.2022.11691 https://bit.ly/3NIlGfL

...Methods...
wave 1, February-September 2020 (wild-type variant);
wave 2, October 2020-July 2021 (Alpha); and
wave 3, August 2021-March 2022 (Delta and Omicron)...

Results
Of 2560 participants, 739 individuals (29%) had COVID-19 (89 asymptomatic), of whom 229 (31.0%...) had long COVID (Table 1)...

The number of vaccine doses was associated with lower long COVID prevalence:
41.8% ... in unvaccinated patients,
30.0% ... with 1 dose,
17.4% ... with 2 doses, and
16.0% ... with 3 doses.
Older age, higher body mass index, allergies, and obstructive lung disease were associated with long COVID.

Discussion
In this longitudinal observational study conducted among health care workers with SARS-CoV-2 infections not requiring hospitalization, 2 or 3 doses of vaccine, compared with no vaccination, were associated with lower long COVID prevalence...
_____________________________________________

Matthew J. @infinitywaltz · 15h
That's a lot more optimistic news than some of the studies showing 10-15 percent reduction (admittedly in an already extremely high-risk population).

WesElyMD @WesElyMD · 15h
Yes and I don’t know if these large numbers will hold up, but on the whole I think the message is in favor of vaccination both to reduce hospitalization and reduce long Covid risk.

1232wonderY
jul 12, 2022, 2:11 pm

I haven’t been following closely. Is there data that suggests which US vaccine booster (Pfizer or Moderna) is more effective against the newest Covid variations?

124margd
Bewerkt: jul 13, 2022, 11:49 am

Sounds like both Pfizer and Moderna are working on bivalent boosters for fall.

Moderna is telling investors (i.e., not peer-reviewed, not even a preprint, but hopefully a good sign):

Moderna Announces Bivalent Booster mRNA-1273.214 Demonstrates Potent Neutralizing Antibody Response Against Omicron Subvariants BA.4 And BA.5
June, 22, 2022

...today announced new clinical data on its bivalent (Omicron) COVID booster candidate, mRNA-1273.214. One month after administration in previously vaccinated and boosted participants, a 50 µg booster dose of mRNA-1273.214 elicited potent neutralizing antibody responses against the Omicron subvariants BA.4 and BA.5 in all participants regardless of prior infection. Based on this and prior data, the Company is working to complete regulatory submissions in the coming weeks requesting to update the composition of the booster vaccine to mRNA-1273.214...

https://investors.modernatx.com/news/news-details/2022/Moderna-Announces-Bivalen...

125John5918
Bewerkt: jul 13, 2022, 9:24 am

I'm currently recovering from COVID which I caught last month, probably on a trip to England. They should issue international health advisories about travelling to these dangerous European countries - much safer to stay at home in Africa!

I'm triple-vaccinated so I didn't get any of the really dangerous COVID symptoms, but it was still pretty nasty - streaming nose, painful hacking cough, bouts of fever, restless nights, general weariness. Like a bad 'flu, but I mean a really bad one.

Two thing struck me. The first was how laid back the doctor was when I tested positive here in Kenya. He gave me a palliative for the cough, told me to eat fruit and drink a lot of water, and to come back in three days if I wasn't feeling any better. Friends in UK and Germany tell me that it's much the same there - take paracetamol, rest, and drink a lot of fluids. The second was to compare getting COVID now, fully vaccinated, with the poor souls who got it two years ago when there were no vaccinations, or even worse, the people who for whatever misguided reasons refused vaccination and consequently died. What a waste of human life.

Still quite weary at times, but people I know who've had it recently say it can take weeks to get back to normal, so I can't complain.

126margd
jul 13, 2022, 11:05 am

>125 John5918: Rest. Pace yourself.

(I saw a preprint that suggested Long Covid more likely if you don't. Will post if I find it.)

127margd
jul 13, 2022, 11:54 am

>124 margd:

Moderna to make two different omicron boosters: one for US, another for UK, EU
Moderna says its BA.1-targeting vaccine boosts protection against BA.4/5.
Beth Mole - 7/11/2022

The type of COVID-19 booster dose you get later this year could depend on where you live.

Vaccine-maker Moderna is working up two omicron-targeting boosters for different countries. If the company's plans pan out, it will mark the first time that COVID-19 vaccines would target different versions of the pandemic coronavirus in different places. Until now, all vaccines, including boosters, have targeted the ancestral strain of SARS-CoV-2, first identified in Wuhan, China.

Both of Moderna's next-gen booster candidates are bivalent vaccines, which target both the ancestral virus and some version of omicron. One booster option targets BA.1—the version of omicron that first burst out of South Africa last November, causing a towering wave of infection in the US in January 2022. That BA.1-based next-gen booster could be available in the EU, UK, Australia, and elsewhere later this month or early August. (Moderna says its BA.1-targeting vaccine boosts protection against BA.4/5.) Moderna's other booster option targets BA.4/5 and is intended for use in the US. However, it likely won't be ready until early to mid-fall.

The US split follows guidance from the US Food and Drug Administration, which late last month specifically advised vaccine makers to develop bivalent vaccines that target BA.4/5. The regulator based its recommendation on feedback from a committee of expert advisers. The committee voted 19 to 2 in support of updating fall boosters to target some version of omicron, with advisers informally expressing consensus that the boosters should be bivalent and target BA.4/5.

BA.4 and BA.5, which share the same spike protein mutations, are gaining dominance worldwide. In the US, BA.5 is now accounting for an estimated 54 percent of infections, according to the Centers for Disease Control and Prevention. With BA.1 no longer circulating in the US, advisers felt a BA.4/5-targeting vaccine would offer the best boost of protection for the fall...

https://arstechnica.com/science/2022/07/moderna-to-make-two-different-omicron-bo...

128margd
jul 26, 2022, 11:56 am

Roger Chou et al. 2022. Update Alert 8: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings (Letter). Annals of Internal Medicine, 26 July 2022. https://doi.org/10.7326/L22-0272

129margd
jul 26, 2022, 12:41 pm

Eric Topol and Akiko Iwasaki. 2022. Operation Nasal Vaccine--Lightning Speed to Counter COVID-19. Science Immunology, 21 July 2022. DOI:10.1126/sciimmunol.add9947

130margd
jul 29, 2022, 10:06 am

Could Genetics Be the Key to Never Getting the Coronavirus?
Scientists have known for decades that some people can be resistant to HIV infection (malaria, etc.). Why not the coronavirus, too?
Katherine J. Wu | July 25, 2022

...With COVID-19, too, researchers have started to home in on some trends. Casanova, at Rockefeller, is one of several scientists who has led efforts unveiling the importance of an alarm-like immune molecule called interferon in early control of infection. People who rapidly pump out gobs of the protein in the hours after infection often fare just fine against the virus. But those whose interferon responses are weak or laggy are more prone to getting seriously sick; the same goes for people whose bodies manufacture maladaptive antibodies that attack interferon as it passes messages between cells. Other factors could toggle the risk of severe disease up or down as well: cells’ ability to sense the virus early on; the amount of coordination between different branches of defense; the brakes the immune system puts on itself, so it does not put the host’s own tissues at risk. Casanova and his colleagues are also on the hunt for mutations that might alter people’s risk of developing long COVID and other coronaviral consequences. None of these searches will be easy. But they should be at least simpler than the one for resistance to infection, Casanova told me, because the outcomes they’re measuring—serious and chronic forms of disease—are that much more straightforward to detect...

https://www.theatlantic.com/health/archive/2022/07/why-some-people-never-get-cov...

131margd
jul 29, 2022, 1:22 pm

"conducting a rapid antigen test immediately before departure reduces post-arrival transmission between 37.4%... and 46.7% ..."

Testing people hours before an event can reduce COVID-19 transmission: study
https://www.ctvnews.ca/health/testing-people-hours-before-an-event-can-reduce-co...

Chad R. Wells et al. 2022. Testing for COVID-19 is Much More Effective When Performed Immediately Prior to Social Mixing. Int J Public Health, 27 July 2022. https://doi.org/10.3389/ijph.2022.1604659
https://www.ssph-journal.org/articles/10.3389/ijph.2022.1604659/full

Abstract
...Results: Depending on the rapid antigen test used, conducting a rapid antigen test immediately before departure reduces post-arrival transmission between 37.4%... and 46.7% ... , compared to a 31.1% ... reduction using an RT-PCR 12 h before arrival. Performance of each rapid antigen test differed by diagnostic sensitivity over the course of disease. However, these differences were smaller than those engendered by testing too early.

Conclusion: Testing closer to arrival—ideally on the day of arrival—is more effective at reducing post-arrival transmission than testing earlier. Rapid antigen tests perform the best in this application due to their short turnaround time.

132margd
jul 29, 2022, 2:11 pm

Elementary school project:

Learning about Air Purification during a Global Pandemic
David McFall, Principal Pierre Elliott Trudeau Elementary School, Gatineau, Quebec | February 24, 2022

https://petes.westernquebec.ca/learning-about-air-purification-during-a-global-p...

133margd
aug 5, 2022, 11:10 am

Eric Topol (Scripps MD-scienist) @EricTopol | 6:30 PM · Aug 4, 2022:
New @TheLancet--The first prospective study of #LongCovid with symptoms documented before Covid and w/age and sex-matched controls

1 in 8 people (12.7%) developed Long Covid after #SARSCoV2 infections
Highlighted abstract ( https://twitter.com/EricTopol/status/1555320217827307520/photo/1 )
-----------------------------------------------------------

Aranka V Ballering et al. 2022. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. The Lancet, Volume 400, ISSUE 10350, P452-461, August 06, 2022. DOI:https://doi.org/10.1016/S0140-6736(22)01214-4 https://thelancet.com/journals/lancet/article/PIIS0140-6736(22)01214-4/fulltext

Summary
...COVID-19 diagnoses (due to SARS-CoV-2 alpha (B.1.1.7) variant or previous variants)

Findings
76 422 participants (mean age 53·7 years ..., 46 329 (60·8%) were female) completed a total of 883 973 questionnaires. Of these, 4231 (5·5%) participants had COVID-19 and were matched to 8462 controls. Persistent symptoms in COVID-19-positive participants at 90–150 days after COVID-19 compared with before COVID-19 and compared with matched controls included chest pain, difficulties with breathing, pain when breathing, painful muscles, ageusia or anosmia, tingling extremities, lump in throat, feeling hot and cold alternately, heavy arms or legs, and general tiredness. In 12·7% of patients, these symptoms could be attributed to COVID-19...

134margd
Bewerkt: aug 10, 2022, 8:25 am

Long Covid: A parallel pandemic (19:41)
Hunni Media for Knowable Magazine | 08.08.2022

VIDEO: Tens of millions of people are living with long Covid. Yale immunologist Akiko Iwasaki explains the current state of play in the search for causes of, and treatments for, this potentially debilitating illness.

https://knowablemagazine.org/article/health-disease/2022/long-covid-parallel-pan...

135margd
aug 10, 2022, 10:17 am

Marie Snyder @MarieSnyder27 | 9:03 AM · Aug 8, 2022:
(Retired teacher) I write, paint, build stuff, and read on politics, philosophy, human nature, and art. Campaigning for (School) Trustee in Waterloo/Wilmot (Ontario).

One school has been 100% Covid-free with 0 learning loss: Good masks indoors, zero 'mask breaks,' everyone eats outdoors even in bad weather, every room has a HEPA or CR-box and CO2 monitor, at 650 windows open, and at 800 students vacate the room. 1/8

A COVID-Free School? (Abrome, Texas) Here’s How
Tasmanian Times | July 21, 2022
https://tasmaniantimes.com/2022/07/a-covid-free-school-heres-how/

It helps significantly that they acknowledge that "There is no such thing as a harmless single case of COVID" because of the potential for long-term effects on kids, seeding a super-spreader event, and/or hosting a mutation. I feel a mix of vindication, jealousy, and trauma. 2/8

Trauma as in "lasting emotional response after a distressing event" - I can't shake that day that my CO2 monitor read over 2,000 and, after a complaint, admin marched down to my classroom during class to tell me students can't learn with the windows open 1/2" - and then 3/8

discovered my contraband CR box (Corsi Rosenthal air filtration box, cleanaircrew.org) and demanded that I remove it at once. They were pleasant about it all, but after 2 years of Covid, they still didn't know what a CO2 monitor was for, and didn't seem to care. And I don't see signs of it improving. I left shortly later. 4/8

I was, and still am, unable to process schools operating in a way that potentially harms kids, ignorant of the need for masks, ventilation, and filtration. Any suggestion was met with eye-rolling or "it isn't your place to tell us anything" as I pleaded for protections. 5/8

We have to follow the science, not the politicking. We're overfilling hospitals, and the valleys in our graphs are higher than previous peaks! Pretending it's fine doesn't make it safe. But I have no idea how to convince people in charge. 6/8
Graph Cdn hospitalisations ICU
( https://twitter.com/MarieSnyder27/status/1556627128422129669/photo/1 )

At least retirement might persuade people it wasn't just about keeping ME safe - It's as unnerving to watch kids completely unprotected after masks were removed as it would be watching them play in traffic. In Ontario this month, Covid deaths were over 7x car collisions. 7/8

We wouldn't think of putting our kids in an unsafe car without at least a seatbelt in place. We need to bring back mask mandates with N95s, allow CR boxes and open windows, and ensure all staff understand the science. 8/8

137margd
Bewerkt: aug 14, 2022, 8:06 am

US FDA's new recommendations for emerging from quarantine below. More consistent with the science Mina thinks than CDC's (5 days, no testing required). Also w Biden's practice although he took Paxlovid and was susceptible to rebound.

Reduce Your Risk of False Negative: FDA Safety Communication
Date Issued August 11, 2022

Perform repeat, or serial testing following a negative result on any at-home COVID-19 test, whether or not you have symptoms.

The U.S. Food and Drug Administration (FDA) is advising people to perform repeat, or serial, testing following a negative result on any at-home COVID-19 antigen test, to reduce the risk an infection may be missed (false negative result) and to help prevent people from unknowingly spreading the SARS-CoV-2 virus to others. The FDA recommends repeat testing following a negative result whether or not you have COVID-19 symptoms...

...use multiple tests over a certain time period, such as 2-3 days, especially when the people using the tests don't have COVID-19 symptoms...

https://www.fda.gov/medical-devices/safety-communications/home-covid-19-antigen-...
___________________________________________________

Apurv Soni et al. 2022. Performance of Screening for SARS-CoV-2 using Rapid Antigen Tests to Detect Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infection: findings from the Test Us at Home prospective cohort study. MedRxiv 6 Aug 2022. doi: https://doi.org/10.1101/2022.08.05.22278466 https://www.medrxiv.org/content/10.1101/2022.08.05.22278466v1

This article is a preprint and has not been peer-reviewed

Abstract
...Meaning To optimize detection of SARS-CoV-2 infection with home antigen tests, people suspected to be infected with SARS-CoV-2 virus should test twice at least 48-hours apart if they are symptomatic and three times at 48-hour intervals if they do not have symptoms (asymptomatic).
_____________________________________________________

Michael Mina (frmer Harvard prof) @michaelmina_lab | 11:30 PM · Aug 11, 2022:
https://twitter.com/michaelmina_lab/status/1557932455885258753

Remarkable day for COVID #rapidtests
A Thread on @US_FDA NEW GUIDANCE!
FDA finally recognized Sensitivity of test *REGIMEN* is as/more important than single test
Sort of recognized virus load goes up & impacts Rapid Tests!
Sounds familiar! (ca 2020)
1/

Michael J. Mina, M.D. et al. 2022. Rethinking Covid-19 Test Sensitivity — A Strategy for Containment (Perspective). N Engl J Med 3 Sept 2020; 383:e120 DOI: 10.1056/NEJMp2025631 https://www.nejm.org/doi/full/10.1056/NEJMp2025631

138margd
aug 15, 2022, 8:20 am

Table at bottom of USFDA website give extended expiration dates by brand & lot number for COVID home tests:

https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/hom...

139margd
aug 15, 2022, 9:47 am

Cecília Tomori et al. 2022. Where is the “Public” in American Public Health? Moving from individual responsibility to collective action (Comment). The Lancet's EClinicalMedicine: Volume 45, 101341, March 01, 2022. DOI:https://doi.org/10.1016/j.eclinm.2022.101341 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00071-2/fullt...

American individualism continues to prove incommensurate to the public health challenge of COVID-19. Where the previous US Administration silenced public health science, neglected rising inequalities, and undermined global solidarity in the early pandemic response, the Biden Administration has sought to take action to respond to the ongoing pandemic. However, the Administration's overwhelming focus on individual responsibility over population-level policy stands in sharp contrast to fundamental tenets of public health that emphasize “what we, as a society, do collectively to assure the conditions for people to be healthy”...When this misalignment of individual responsibility and public health initially became clear with the removal of mask guidance for vaccinated individuals in May 2021, we decried the CDC Director's public admonition: “Your health is in your hands.”...We argued that such statements – coupled with the label of “the pandemic of the unvaccinated” – represent a moral failing of US policy because they “undermine the fundamental notion that all people are equal in dignity and rights”... and implicitly shift blame to individuals for systemic failures...

140margd
aug 15, 2022, 9:52 am

Maria Van Kerkhove @mvankerkhove | 2:09 AM · Aug 7, 2022:
Infectious Disease Epidemiologist; COVID-19 Technical Lead, Emerging Diseases and Zoonoses Lead, WHO Health Emergencies Programme.

The next weeks & months are critical to be vigilant for #COVID19

As individuals:
get vaccinated and take measures to reduce risk of (re)infection.
Mask indoors when around others outside your immediate family.
Distance.
Test.
Ventilate.
Wash hands.
Live life safely.
Be kind.

Governments:
reinforce surveillance, testing, sequencing, access to treatments & O2, vaccinate all at risk,
surge capacities and PPE,
invest in ventilation & in a strong protected work force.
Ensure policies are agile to deal with epi, capacities & financial needs;
continue to invest in research of this virus and its many variants and continue to develop new tools;
support patients with Post COVID-19 condition (#LongCovid);
fight the infodemic and misinformation;
communicate regularly and openly and rebuild trust;
share successes.

#COVID19 is not over but we have the tools to end this pandemic. We all continue to have an important role to play.

WHO is here to work with everyone, everywhere to end the global emergency … everywhere.

141margd
aug 16, 2022, 1:55 pm

Coronavirus spike protein activated natural immune response, damaged heart muscle cells
American Heart Association Basic Cardiovascular Sciences Meeting – Presentation: P3119
July 25, 2022

Research Highlights:
Researchers have demonstrated for the first time a potential route of the SARS-CoV-2 spike protein damaging the heart.
In study evaluating mice and human heart cells, the SARS-CoV-2 spike protein inflamed the heart muscle cells, which can lead to heart injury...

...The researchers studied whether the SARS-CoV-2 spike protein activates the natural immune response in heart muscle cells. HCoV-NL63 is a {human cold?} coronavirus that infects the respiratory system without causing cardiac injury, although its spike protein also uses ACE2 to mediate virus entry. They studied the potential ability to cause heart disease of both SARS-CoV-2 spike protein and the NL63 spike protein. Their results showed that the SARS-CoV-2 spike protein activated the natural immune response in heart muscle cells and damaged the heart, but the NL63 spike protein did not.

“The fact that the SARS-CoV-2 spike protein is activating the natural immune response may explain the high virulence compared to the other coronaviruses,” Lin said. ...

https://newsroom.heart.org/news/coronavirus-spike-protein-activated-natural-immu...

142margd
aug 16, 2022, 2:03 pm

"Compared with healthy controls, the capillary density of #LongCovid patients was decreased by 41%"
"Our data strongly suggest that COVID leaves persistent capillary rarefication {less dense} even 18 months after infection"

Irina Osiaevi et al. 2022. Persistent capillary rarefication in long COVID syndrome. Angiogenesis (11 Aug 2022) https://link.springer.com/article/10.1007/s10456-022-09850-9

143margd
aug 17, 2022, 2:45 pm

Trial finds 100-year-old tuberculosis vaccine offers protection against COVID to high-risk patients and may help with other infectious diseases
Ciara Linnane | Aug. 17, 2022

...Data from a trial seeking to determine whether multiple injections of a tuberculosis vaccine developed in the 1900s could protect high-risk diabetes patients from COVID produced some positive results, according to a study in Cell Medicine Reports.

The trial tracked COVID infections among a group of 144 participants, all of whom had Type 1 diabetes, with two-thirds receiving at least three doses of BCG, or Bacillus-Calmette-Guerin, shots, which protect people by bolstering the immune system, according to the study, as the New York Times reported.

The results found just 1% of the 96 people who got the BCG shots developed COVID, while 12% of the placebo recipients contracted the illness.

“The BCG group also displays fewer infectious-disease symptoms and lesser severity, and fewer infectious-disease events per patient, including COVID-19,” the authors wrote. “There were no BCG-related systemic adverse events. BCG’s broad-based infection protection suggests that it may provide platform protection against new SARS-CoV-2 variants and other pathogens.”

The BCG shots are still given to infants in parts of the world that continue to record TB cases...

https://www.marketwatch.com/story/trial-finds-100-year-old-tuberculosis-vaccine-...
-------------------------------------------------------------------

Denise L. Faustman et al. 2022. Multiple BCG vaccinations for prevention of COVID-19 and other infectious diseases in Type 1 diabetes. Cell Reports Medicine: August 15, 2022 DOI:https://doi.org/10.1016/j.xcrm.2022.100728 https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(22)00271-3

Highlights
• We report on our randomized trial of multi-dose BCG for protection against COVID-19
• BCG is safe and has 92% efficacy versus placebo against COVID-19
• Findings also suggest platform protection against additional infectious diseases
• Efficacy takes 1-2 years to manifest, but the protection may last decades

144margd
aug 22, 2022, 10:00 am

Amanda Hu @amandalhu | 9:33 PM · Nov 12, 2021:
https://twitter.com/amandalhu/status/1459348551897534468

V3.0 of the "Barriers to Air Purifiers in Schools Rebuttal Matrix"/"Parental/Teacher Fatigue Reducer"
Edits:
Added new specific concerns to electrical grid, fans; rebuttal for other mitigations
Image link and cc license info: https://flic.kr/p/2mJjaMR *
...
Image ( https://twitter.com/amandalhu/status/1459348551897534468/photo/1 )
----------------------------------------------------------------------

* Rebuttal Matrix for advocates of Air Filtration in Schools Based on Common Barriers
V 3.0 by Amanda Hu
https://www.flickr.com/photos/23309579@N04/51674665687/in/photostream/

145Molly3028
aug 22, 2022, 12:09 pm

https://www.mediaite.com/news/breaking-dr-anthony-fauci-to-step-down/
BREAKING: Dr. Anthony Fauci to Step Down

Dr. Anthony Fauci, the White House’s Chief Medical Advisor and Director of the NIAID, will step down from his role in the government at the end of the year.

146margd
Bewerkt: aug 23, 2022, 2:39 am

Regular physical activity may lessen Covid risks, study finds
The research suggested exercise could affect the severity of infection, rates of hospitalisation and death
Andrew Gregory | 22 Aug 2022. Last modified on Tue 23 Aug 2022

Regular physical activity is linked to a lower risk of Covid-19 infection, severity, hospitalisation and death...

A weekly total of 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity physical activity appears to afford the best protection...

...The link between regular physical activity and Covid-19 severity is poorly understood, but probably involves both metabolic and environmental factors, say the researchers, who set out to try to quantify the threshold of physical activity that might be needed to lessen the risks of infection and associated hospital admission and death....

https://www.theguardian.com/world/2022/aug/22/regular-physical-activity-may-less...
----------------------------------------------------

Robert Sallis et al. 2022. Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48 440 adult patients. British Journal of Sports Medicine Volume 55, Issue 19 https://bjsm.bmj.com/content/55/19/1099

Abstract
..Results Patients with COVID-19 who were consistently inactive had a greater risk of hospitalisation (OR 2.26...), admission to the ICU (OR 1.73...) and death (OR 2.49...) due to COVID-19 than patients who were consistently meeting physical activity guidelines. Patients who were consistently inactive also had a greater risk of hospitalisation (OR 1.20...), admission to the ICU (OR 1.10...) and death (OR 1.32...) due to COVID-19 than patients who were doing some physical activity.

Conclusions Consistently meeting physical activity guidelines was strongly associated with a reduced risk for severe COVID-19 outcomes among infected adults. We recommend efforts to promote physical activity be prioritised by public health agencies and incorporated into routine medical care.

147margd
aug 24, 2022, 8:15 am

Biden Administration Plans for New Booster Campaign Soon After Labor Day
Sharon LaFraniere and Noah Weiland | Aug. 23, 2022

...Dr. Peter Marks, the top vaccine regulator for the Food and Drug Administration, said in an interview on Tuesday that while he could not discuss timing, his team was close to authorizing updated doses that would target the versions of the virus now circulating.

Even though those formulations have not been tested in humans, he said, the agency has “extremely good” data showing that the shots are safe and will be effective. “How confident am I?” he said. “I’m extremely confident.”

...In a sign of impending action from the F.D.A., the Centers for Disease Control and Prevention has scheduled a two-day meeting of its advisory panel of experts on the matter for Sept. 1 and 2. The C.D.C. director, Rochelle P. Walensky, would then make a final decision on whether to roll out the new doses. Shipments to states could begin as early as next week, according to officials familiar with the plan.

The government plans to offer the new Pfizer booster to everyone 12 and older while limiting the new Moderna shot to adults. People who have already received the initial two-shot series of either vaccine would be eligible. So would those who have received the initial shots plus one or two booster shots. The new booster campaign could be broadened to younger children later.

Dr. Marks suggested that the biggest obstacle to the effort was the level of complacency that had set in, even as the pandemic continued to exact what he called an “unacceptable” death toll.

He said the F.D.A. might recommend that people who had recently received a Covid vaccine dose wait “a few months” before getting the new shot, even if they were otherwise eligible. He said the C.D.C. might weigh in on whether people who were recently infected with the virus should also wait...

https://www.nytimes.com/2022/08/23/us/politics/covid-booster-shots-biden.html
---------------------------------------------------------

Eric Topol (Scripps) @EricTopol | 11:48 PM · Aug 23, 2022:
...Here are some thoughts on the potential merits and disadvantages for this plan
Table ( https://twitter.com/EricTopol/status/1562285788045266944/photo/1 )

148margd
aug 25, 2022, 5:00 am

Israeli study shows Pfizer COVID pill of no benefit in younger adults
MATTHEW PERRONE \ 25 Aug 2022

Results from 109,000-patient study show drug still reduces risk of hospitalization, death for high-risk seniors, raises questions on use in US, where it has become a go-to treatment.

...The researchers found that Paxlovid reduced hospitalizations among people 65 and older by roughly 75% when given shortly after infection. That’s consistent with earlier results used to authorize the drug in the US and other nations.

But people between the ages of 40 and 65 saw no measurable benefit, according to the analysis of medical records...

https://www.timesofisrael.com/israeli-study-shows-pfizer-covid-pill-of-no-benefi...
------------------------------------------------------------------

Ronen Arbel et al. 2022. Nirmatrelvir {Paxlovid} Use and Severe Covid-19 Outcomes during the Omicron Surge. NEJM August 24, 2022. DOI: 10.1056/NEJMoa2204919 https://www.nejm.org/doi/full/10.1056/NEJMoa2204919

149margd
aug 25, 2022, 10:39 am

Tori L. Cowger et al. 2022. Impact of Lifting School Masking Requirements on Incidence of COVID-19 among Staff and Students in Greater-Boston Area School Districts: A Difference-in-Differences Analysis. MedRxiv 9 Aug 2022. 23p. https://doi.org/10.1101/2022.08.09.22278385 https://www.medrxiv.org/content/10.1101/2022.08.09.22278385v1.full.pdf

Preprint. Not yet peer-reviewed.

ABSTRACT
...Results. Before the statewide school masking policy was lifted, there was no statistically significant
difference in case rate trajectories between school districts. However, weekly and cumulative case
rates were significantly higher in students and staff in school districts that removed masking
requirements, compared to districts that had not yet lifted requirements. We estimate that lifting of
school masking requirements was associated with an additional 44.9 (95% CI: 32.6, 57.1) COVID-19
cases per 1,000 students and staff over the 15 weeks since the lifting of the statewide school masking
requirement, representing nearly 30% of all cases observed in schools during that time. School districts that sustained masking requirements for longer periods tended to have older school buildings in poorer condition, more crowded classrooms, higher proportion of low income and English learning students and students with disabilities, and a higher proportion of Black and Latinx students and staff.

Conclusions. Masking is a relatively low-cost but effective intervention that can protect students and
staff from substantial illness and loss of in-person days in school. Despite compelling evidence that
masking significantly reduces the spread of SARS-CoV-2, political will and public adherence to masking
has waned. Our study confirms that universal masking requirements can benefit all students and staff,
and therefore represents an important strategy to mitigate the impacts of structural racism, ensure
health equity, and to avoid potential deepening of educational inequities.

150margd
aug 25, 2022, 11:15 am

Several antidepressants can have protective effects against severe COVID outcomes (ER visits, hospitalizations).


Bradley A. Fritz et al. Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2. Translational Psychiatry volume 12, Article number: 341 (22 Aug 2022) https://nature.com/articles/s41398-022-02109-3

Abstract
...only observed with daily doses of at least 20 mg fluoxetine-equivalent ..., but not with daily doses lower than 20 mg fluoxetine-equivalent... In exploratory secondary analyses, the outcome incidence was also reduced with exposure to selective serotonin reuptake inhibitors ..., bupropion ..., and FIASMA antidepressant drugs .... Antidepressant exposure was associated with a reduced incidence of emergency department visitation or hospital admission among SARS-CoV-2 positive patients, in a dose-dependent manner... These data support the FIASMA (functional inhibition of acid sphingomyelinase activity) model of antidepressants’ effects against COVID-19.

...In conclusion, pre-illness exposure to antidepressants was associated with a decreased odds of ED visitation or hospital admission among ambulatory patients infected with SARS-CoV-2. This association appears to be related to exposure to SSRIs (selective serotonin reuptake inhibitors) and in particular to the agents with FIASMA activity. When designing future prospective studies, researchers should consider SSRIs and other antidepressants with FIASMA activity as candidate interventions for outpatient therapy of COVID-19, prescribed at a dose f at least 40 mg/day of fluoxetine-equivalents.

151margd
aug 25, 2022, 11:41 am

Jenny C. Jin et al. 2022. SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy. Pediatric Research (19 Aug 2022) https://www.nature.com/articles/s41390-022-02266-7

Abstract
Background
In utero transmission of SARS coronavirus 2 (SARS-CoV-2) has not been fully investigated. We investigated whether newborns of mothers with COVID-19 during pregnancy might harbor SARS-CoV-2 in the gastrointestinal tract.

Methods
This cohort study investigated stool from 14 newborns born at 25–41 weeks admitted at delivery to our urban academic hospital whose mothers had COVID-19 during pregnancy. Eleven mothers had COVID-19 resolved more than 10 weeks before delivery. Newborn stool was evaluated for SARS-CoV-2 RNA, Spike protein, and induction of inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) in macrophages.

Results
Despite negative SARS CoV-2 nasal PCRs from all newborns, viral RNAs and Spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life and increased over time in 6. Stool homogenates from all 14 newborns elicited elevated inflammatory IL-6 and IFN-γ from macrophages. Most newborns were clinically well except for one death from gestational autoimmune liver disease and another who developed necrotizing enterocolitis.

Conclusions
These findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal viral reservoirs in the newborns. Further investigation is required to understand the mechanisms and their clinical implications.

Impact
SARS-CoV-2 RNAs or Spike protein was detected in the stool of 11 out of 14 preterm newborns born to mothers with resolved COVID-19 weeks prior to delivery despite negative newborn nasal PCR swabs.

These novel findings suggest risk of in utero SARS-CoV-2 transmission to the fetal intestine during gestation.

The presence of SARS-CoV-2 RNAs and Spike protein in the intestines of newborns may potentially impact the development of the gut microbiome and the immune system; the long-term health impact on the preterm infants should be further investigated.

152stellarexplorer
aug 25, 2022, 2:52 pm

>150 margd: This is interesting. I have wondered throughout the pandemic as fluvoxamine seemed to be of some degree of help, however modest, what might be distinctive about that medicine over several others that are similar. My working assumption was possibly not much. This study supports that idea.
It also makes me wonder - anecdotal observation of course - whether this in part explains the low incidence of Long Covid among my patients on antidepressants. Obviously there might be many other factors....

153margd
aug 25, 2022, 6:09 pm

>152 stellarexplorer: Hmm--any downsides to antidepressants?

{Just kidding! Sort of... Yeah, really, just kidding.}

154stellarexplorer
aug 26, 2022, 8:04 pm

>153 margd: Not if unnecessary :)
Compared to Covid….? Yeah, prefer two weeks of antidepressant

155margd
jan 24, 9:45 am

>54 margd: Jan Choutka...& Akiko Iwasaki. 2022. Unexplained post-acute infection syndromes (Review). Nature Medicine volume 28, pages 911–923 (18 May 2022) https://www.nature.com/articles/s41591-022-01810-6
-------------------------------------------------------
Twitter summary:

Emmanuel @ejustin46 | 12:37 AM · Jan 22, 2024
https://twitter.com/ejustin46/status/1749305285326340597/photo/1
https://threadreaderapp.com/thread/1749305273154420884.html

UNEXPLAINED POST-ACUTE INFECTION SYNDROMES
A very interesting study of Akiko {Iwasaki} @VirusesImmunity

WHICH INFECTIONS ?
Table 1. unexplained PAISs associate w acute infections
https://twitter.com/ejustin46/status/1749305273154420884/photo/1

2) WHICH SYMPTOMS ?
Box 2. main symptoms
https://twitter.com/ejustin46/status/1749305278778986919/photo/1

3) WHICH SYMPTOMS by infection
https://twitter.com/ejustin46/status/1749305285326340597/photo/1

4) HOW LONG ?
https://twitter.com/ejustin46/status/1749305285326340597/photo/1

5) WHY ?
1st hypothesis : Pathogens reservoirs or remnants
https://twitter.com/ejustin46/status/1749305285326340597/photo/1

6) WHY ?
2nd hypothesis: Dysbiosis/reactivation
https://twitter.com/ejustin46/status/1749305285326340597/photo/1

7) WHY ?
3rd hypothesis : Autoimmunity
https://twitter.com/ejustin46/status/1749305285326340597/photo/1

8) WHY ?
4th hypothesis : Tissue damage
https://twitter.com/ejustin46/status/1749305285326340597/photo/1

Dit onderwerp werd voortgezet door SARS-CoV-2 and COVID-19 (30...).