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)

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 Image
3/ Severe disease is marked by attenuated early interferon response and related elevation of certain inflammatory markers

Also see a late uncoordinated adaptive immune response Image
4/ We then review the major clinical trials and series for immunomodulatory agents to date, including steroids, tocilizumab, interferons, and other agents.

We find: strong evidence for steroids later in disease

No evidence to support tocilizumab at any stage
5/ Reported benefit of baricitinib but no peer reviewed clinical data yet so unclear how it should be deployed and whether it will have an additive effect to steroids

No data to support interferon therapy for COVID-19, but reason to wonder if there might be a role if given early
6/ The accumulating evidence suggests a viral & immune-dysregulated phase, with timing of administration during illness course likely to be a key determinant of effectiveness of either antiviral or immunomodulatory therapy. This figure by @RMKGandhi summarizes this theory nicely Image

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More from @EricMeyerowitz

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

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
3/ We review viral and host factors that impact transmission

Children under ten appear half as susceptible but relative probability of transmission from children compared with adults not well understood

Virus with D614G mutation is associated with higher in vivo viral loads
Read 14 tweets
21 Aug
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

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…
3/ Our understanding of the symptom spectrum of SARS-CoV-2 infection has evolved over the last 9 months, with anosmia and GI symptoms often not included in early reports. By not including these mild or atypical symptoms, the estimated asymptomatic fraction may be overestimated
Read 7 tweets
23 Jun
Thoughts on RECOVERY preprint: dexamethasone as treatment for COVID-19 @AaronRichterman medrxiv.org/content/10.110…
Read 25 tweets
15 May
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
3/ They recruited 20 patients who recovered from COVID-19 (all IgG positive) and collected blood samples 20-35 days after symptom onset when all patients were asymptomatic.
Read 17 tweets
26 Apr
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 Image
They note that adaptive immune responses were found to be protective for SARS-CoV and suggest CD4 T cell responses may be important for generation of neutralizing antibodies
Read 9 tweets

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