1/ Thoughts on the exciting world of tocilizumab for treatment of COVID-19.

RECOVERY tocilizumab preprint posted earlier today is another landmark paper and an enormous contribution to our expanding COVID-19 treatment playbook

medrxiv.org/content/10.110… 2/ A quick review of 7 prior tocilizumab RCTs

First COVACTA which found no benefit with tocilizumab

medrxiv.org/content/10.110…

1/ Key question right now is how much SARS-CoV-2 vaccines will decrease transmission.

Data from Regeneron mAb cocktail prevention press release may help us think about this

investor.regeneron.com/news-releases/… 2/ They report their mAb cocktail had 100% efficacy in preventing symptomatic COVID-19 (8/223 placebo vs. 0/186 REGEN-COV)

They also report lower ASYMPTOMATIC infection (15/223 placebo vs. 10/186 REGEN-COV)

1/ We've learned so much since the beginning of the pandemic, but we still have not well defined the persistently asymptomatic fraction

Why is it important to describe this group and what are the limitations to doing so thus far? A thread 😷😷

sciencedirect.com/science/articl… 2/ An early transmission report of suggested transmission is possible prior to symptom onset.

Need to distinguish between: persistently asymptomatic infection (no symptoms attributable to the virus for the duration of infection) and presymptomatic state

nejm.org/doi/full/10.10…

1/ New in CID, our review of immunomodulation as treatment for COVID-19 with @Arthur_Kim_ID, Michael Mansour, and a great team (mostly not on twitter)

academic.oup.com/cid/advance-ar… 2/ We start with a narrative review of immune changes in severe COVID-19.

Earlier it was considered a possible "cytokine storm," but now strong evidence that it is a more complex immune dysregulation

Mild dz = early, effective innate and coordinated adaptive immune response

1/ Our comprehensive review of transmission of SARS-COV-2 is out in @AnnalsofIM with @AaronRichterman @RMKGandhi @PaulSaxMD

acpjournals.org/doi/10.7326/M2… 2/ We review environmental viability of virus in experimental and real world settings.

RNA reported in many real world studies, but at very low copy counts

Viable virus assessed for only rarely and in those instances only isolated occasionally, also at very low levels

1/ In new preprint w/ @AaronRichterman @mugecevik @BogochIsaac @nicolamlow we argue limitations to understanding true asymptomatic fraction:

1) Inconsistent sx reporting

2) Inadequate f/u time to exclude "pre-symptomatic" ppl

3) Issues w/ serosurveys

papers.ssrn.com/sol3/papers.cf… 2/ Wide range of asymptomatic proportion reported in the literature from 4% to >80%. Systematic reviews provide best estimates and suggest values closer to 20% medrxiv.org/content/10.110…

Thoughts on RECOVERY preprint: dexamethasone as treatment for COVID-19 @AaronRichterman medrxiv.org/content/10.110…

1/ I'm going to try to contain myself, but very important/elegant article out tonight in Cell with potentially critical implications for immunity as well as a possible explanation for differential severity in presentation of COVID-19 @AaronRichterman cell.com/cell/fulltext/… 2/ Multi-institution group used a bioinformatic approach to predict SARS-CoV-2 peptides that would be likely T-cell targets. This approach is well established and validated and predicts 50% of T-cell response in prior models

Potentially very important study with large implications posted to medRxiv on April 22. @AaronRichterman medrxiv.org/content/10.110… This group of researchers from Germany looked for T-cell responses to SARS-CoV-2 among 18 patients with COVID19 and 68 healthy controls. Characteristics of these individuals shown below