Thread by @EricMeyerowitz

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

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

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