Looking for knowledgeable expert responses to:

“CDC guidance on COVID exposure is a mess.”

Here is the true and current scenario - a friend developed COVID 36 hrs after being with me and a group of other friends. What do we do?

🧵(1/ 6) CDC guidance says test at 6 and 8 days. But still wear a mask indoors for 10 days. State websites say the same.

MGH/Brigham website says visitors only need to wear a mask if they have symptoms or tested +.

Doctor and dentist tell me the same for visiting the office. (2/6 )

Full body MRI screening is currently a "thing" thanks to Kim Kardashian. From both a societal and individual level, FB-MRI is problematic. To understand why, consider the "epidemic" of thyroid cancer in Korea, beginning in 1999.

(1/10)nejm.org/doi/full/10.10… In 1999, cancer screening become a major governmental and medical community push in Korea, and many people had thyroid-cancer screening. (2/10)

1/ Posted a commonsense tweet about masking that actually supports the Cochrane report's inconclusive summary - and the outpouring of responses from people who quote the report without reading or understanding it, is simply amazing. 2/Cochrane reviews are highly nuanced and challenging sometimes even for a physician not trained in evidence based medicine. They are also not primary research, but rather an analysis of studies that meet their criteria.

OMG. I was this many years when I learned this: The “A” paper used outside the US from A0 to A4 is designed so that the ratio of sides is ~sqrt(2).That way, cutting the long side in half yields two pieces of the next size down. A0-> 2 x A1 -> 4 x A2, etc. scilogs.spektrum.de/hlf/why-a4-the… So…the short side of one paper becomes the long side of the next paper down, recursively.

1/Paxlovid rebound: with 2/2 in my family with Paxlovid rebound, stories rife on Twitter, and 2 completely unscientific polls showing 46-47% rebound, I am thinking about Paxlovid efficacy in terms of relative risk, absolute risk, and Number Needed to Treat (NNT) 2/ Because the numbers are from many non-comparable studies, this discussion is only directional, but I believe meaningful. Let’s start with the Paxlovid NEJM article. nejm.org/doi/full/10.10…

Heard Rochelle Walensky on CBS on new recommendations. New science - mild infection and 85-90% of transmission in first 5 days; need to keep society open drove change in guidelines.
No rapid test because not sure what to do with the info. 1/To clarify first 5 days from CNN interview - 2 days before symptoms and 3 days after. This is based on what people will tolerate and follow. With Omicron severity as mild, people would feel well enough to work at 5 days and wouldn't tolerate 10 day isolation.

1/ T cell responses in SARS-COV (that is, SARS); paper by coronavirus expert, Stanley Perlman. "our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest... pubmed.ncbi.nlm.nih.gov/25056892/ 2/ ...that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection."
In response to some "immunologists" saying that T cells play no role in immunity to COVID, I have been posting correct info on their important role in preventing severe disease.

1/ Why do I believe Omicron will cause -on average - less severe illness in vaccinated or previously infected people (as it seems to have done in SA)? Quite simply - because of the almost entirely preserved T cell epitopes. Here is a very simplified version of what happens. 2/ Neutralizing Ab to wt and other non-Omicron variants - from infection or vaccination - don’t appear to be enough to protect against infection in most people. So when enough virus gets into the body there aren’t enough nAb to block the virus from infecting epithelial cells.

1) Vaccine Boosters - what does immunology tell us? For people with a normal immune system, a vaccine booster will undoubtedly lead to higher titers and more specific antibodies for the particular antigen injected - in this case, spike protein from the native SARS-CoV2. 2) If some epitopes on the antigen have changed (Delta) but many stay the same and the conformation stays mostly the same, the new antibodies and higher titres will be at least as effective as current protection, and likely much more effective in neutralizing virus.

1) What am I doing personally, with this info? One month ago, I was starting to eat out and go to an occasional group event in one of the most highly vaccinated communities in the US. Today, I am back to wearing masks whenever I go indoors in a public setting. Why? see next.

https://twitter.com/pbleic/status/1419015204923445248

2) Why am I wearing masks in public settings? After all, aren't breakthrough infections "mild." First, COVID has so many complications documented, that I wouldn't want to risk getting (long covid, neurological, lung, cardiac functional deficits). Second...

Breakthrough infections are a very big issue in Israel and likely everywhere with Delta. Viewed together, these two charts show how different it is from this winter's surge. Differences in Delta vs. waning vaccine immunity vs. both?

https://twitter.com/pbleic/status/1419008580058034176

It is the same time scale on the X-axis. The Y-axis in the orange chart is the month that someone got their second vaccination.

1/ This is not good. 55% attack rate of gamma variant in fully vaccinated gold miners, 87% symptomatic. And see next link - Illinois is sequencing 6X more gamma than delta. wwwnc.cdc.gov/eid/article/27… 2/ Illinois sequencing 6X more gamma than delta. And CDC article (see tweet #1)shows that fully vaccinated in close quarters easily get infected. thehill.com/policy/healthc…

1/ The superior low/high dose in the AZ trial was likely completely unexpected, as this dose was NOT planned. It was a dosing mistake. So, here are some questions to consider about the AZ vaccine results:
1. Could low/low dose be even better?
(next) 2/
2. Will AZ go for approval for the estimated 62% efficacy high/high using the Phase III ongoing with that dose?
3. If not, is AZ starting over with protocol amendments?
4. Do they have drug supply for a low/high dose, or can they dilute the existing vials of high dose?

1/ My favorite voice on COVID, ⁦@ashishkjha⁩ paraphrase - with the vaccines, things may start to feel better by Spring and will continue to get better until we no longer feel like we are living in a pandemic. Me- late Spring/early Summer. Why? bostonglobe.com/2020/11/21/nat… 2/ Late Spring/early Summer we start to go outside, schools end, humid weather and many will be vaccinated and, unfortunately, immune from infection. Vaccines will continue all Summer/early Fall, steadily reducing R0.

1/ Exercise and Covid-19: A troubling story from Eric Topol this AM got me thinking about COVID-19 and the risk of exercise during active infection and recovery.

https://twitter.com/EricTopol/status/1302344348755849216?s=20

2/ Four caveats – I don’t know that exercise played a factor here, I am not a cardiologist, this is a personal view not a medical review, and nothing about this constitutes medical advice. Follow my thinking here.

1/ Basics (for non-immunologists) of important new results in COVID-19 immunity. The new finding helps explain how our immune system responds to COVID-19, perhaps why men are more prone to severe COVID-19, and may help make future vaccines more effective. jamanetwork.com/journals/jama/… 2/ Researchers in the Netherlands studied two families that each had two brothers who developed severe COVID-19 at a young age. Since this usually happens in older people, they wanted to understand whether these patients had something wrong with their immune response...

1/ Severe COVID-19 in 2 families was associated with a rare loss of function mutation in TLR7. This Toll-like receptor helps activate the innate immune system to RNA viruses through cytokines and recruitment. Lots to think about and discuss...
jamanetwork.com/journals/jama/… 2/ First, this mutation is rare, and unlikely to be the underlying cause of severe COVID-19. However, it has important implications about how the body fights COVID-19, and even for vaccine development.

1/ Immunology Comix - Summary: 1. Virus must get through mucous membranes, a physical barrier. 2. Innate immunity can destroy virus before it starts. 3. Neutralizing antibodies and memory B cells protect against future infection 4. T cells destroy infected cells 2/Immunology Comix - The first line of defense against respiratory viruses is the mucosal barrier in the nose/lungs. It is a physical defense, later amplified by adaptive mucosal immunity. The cilia, cells and various basement membranes prevent virus from entering the body.