1/n The AZ vaccine adverse effects are seriously concerning. First, since public money flowed into the project through OWS, we need to have access to the data to figure out what happened. If needed, this should be escalated (legally)
2/n Transverse myelitis is a rare event but has been seen with vaccines before. Several questions need to be addressed -/ but systematically
3/n possibility 1: related to previous medical conditions. MS etc. Thats the best case scenario for AZ because one can exclude such patients of detectable
4/n Possibility 2: this is related to the Adenovirus (recall that the Vaccine inoculum is large). That’s not good because several vaccine platforms are based on Adeno systems
5/n Possibility 3: it’s related to a brisk immune system reaction to Spike RBD in general. That’s very bad news. That means the highly adjuvanted Moderna vaccine will also have these effects. Very very concerning
6/n Possibility 4: There was antibody dependent enhancement. Well, not so bad maybe, cos people with high titer Covid antibodies could be excluded.
7/n In all cases, public release of data would be helpful, and serology provided to investigators would be helpful. Plus, we need to exclude the possibility that other vaccines won’t have the same effects.
8/n Thus, any emergency EUA before these issues are resolved seems deeply premature. Any other possibilities that we can think of ?
8/n It would be helpful if a task force of virologists and immunologists could be appointed to suggest possibilities and experiments. Outside the OWS, preferably through NIH

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More from @DrSidMukherjee

17 Jul
@VincentRK @manal_mehta @jhuber 1/n Important discussion with several unresolved questions. First, there are people with T cells to SARS-Cov2 because they have been exposed to other beta-coronaviruses. There is substantial homology in the nucleoproteins. This is shown in 2 papers, including the Nature paper.
@VincentRK @manal_mehta @jhuber 2/n Are these people "immune" to SARS-Cov2 or do they get attenuated disease ? We don't know. Do they spread virus ? We don't know. Intriguingly, the number is around 40% which is around the number that were not infected in the Antarctic cruise.
@VincentRK @manal_mehta @jhuber 3/n Second: we know that the antibody titer AFTER infection has attrition over time, especially if infection is not severe. How do we define "seroprevalence" ? At what cutoff -- since it's a moving target for some people ?
Read 6 tweets
6 Jul
1/n IMPORTANT: Can someone please publish a homology map of all the beta coronaviruses that have been circulating in human populations ?

Why? Because at least 2-3 papers suggest that there is pre-existing immunity, at least CD4/8 cell mediated, because of cross reactivity.
2/n Just two lines of evidence: the Antarctic cruise had 59 percent infection. But what about the other 41 percent ? And the Cell paper by Nusszenweig suggests that at least 40 percent (odd) showed CD4 responses.
3/n Notably, these responses are more capsid directed (and obviously) MHC restricted. As opposed to Spike.
Read 13 tweets
4 May
1/n A rather broad, technical question. There's been a theory going around about BCG being protective of COVID-19 infections
1/2 BCG (the TB vaccine) is known to elicit innate immunity, and people have been discussing whether it is this aspect that is protective.
3/n So what about other vaccines that potently elicit innate immunity. The shingles vaccine (Shingrix) has a very strong adjuvant that it is thought to elicit an innate as well as an adaptive response
Read 5 tweets
2 May
1/n Listen up: I am no huge fan of Remdesivir (full disclosure, I own GILD stock) but if its going to work, it has to be given early
2/n But that means LOTS MORE TESTING AND EARLY INTERVENTION particularly in high risk people (that we know). So, the FDA approval can only work if a LOT more testing was available.
3/n That, in turn, means the number needed to treat to save a life will go up...and that's a decision that we need to take as a society. Right now, it's the ONLY drug that's been shown to work (leave aside the late stages of severe disease).
Read 9 tweets
26 Apr
1/n Listen: this is getting into irritating territory. If you want to re-open business, scientists have offered a plan.
2/n Vastly increase testing. Expensive, but the cost is minimal compared to the losses. Mandatory masking indoors. Mandatory masking on subways and buses.
3/n Wait for drugs and antibodies. Vaccines are 12 months away. Offer subsidies to 1099 workers. Restaurants. Entertainment.
Read 7 tweets
23 Apr
1/n So, the rate of seropositivity in NYC is 20-25%. Not far from what we had guessed. Open the city, and it will be 50%. But that means countenancing another several 1000 deaths.
2/n So..masks, social distancing and school closures must still be in place. New data suggests that subways and closed spaces are sites of infection.
3/n No simple way out of this one. Low tech solutions are probably better. Mask, hand hygeine, distance, isolate the vulnerable. But a 0.7% -1% IFR is what we are looking at.
Read 4 tweets

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