Thread by @WilenLab

Excited to share our new paper led by @chennifer_jen looking at the role of NSAIDs in #COVID19. NSAIDs dampen the cytokine and antibody response to SARS-CoV-2 infection @ASMicrobiology @JVirology @Yale_LabMed @StephanieEisen @YaleIBIO 1/n jvi.asm.org/content/early/…

Early in the pandemic it was suggested NSAIDs could be dangerous in COVID patients by increasing ACE2 expression and thus SARS-CoV-2 replication. Infection does increase expression of the NSAID target PTGS2 (COX-2) 2/n

NSAIDs do not affect ACE2 expression in vitro or in mice 3/n

NSAIDs also do not affect viral replication in cell lines or mice. 4/n

Since NSAIDs are commonly used anti-inflammatory drugs we asked what the NSAID meloxicam does to the immune response to SARS-CoV-2 in K18-hACE2 mice. Meloxicam reduced pro-inflammatory cytokines induced by infection including IL1b, IL6, CCL2, IL2 and TNFa 5/n

NSAIDs did not have a major effect on myeloid or lymphod cell abundance or activation state in infected mice. 6/n

Surprisingly (to us at least), meloxicam significantly reduced neutralizing antibodies made in response to natural SARS-CoV-2 infection 7/n

So what does this mean? Chronic NSAIDs may reduce the immune response to SARS-CoV-2 infection in people. Is this good or bad? It probably depends (as for dexamethasone) on dose/timing. Antibodies are good but high antibody levels correlate with severe disease @VirusesImmunity 8/n

What's still unknown? Does the dampened antibody response from NSAIDs impair the durability or magnitude of protection to reinfection? Do NSAIDs impair antibody response to vaccination? Does short term NSAID use or other NSAIDs do the same? Also true in humans? Stay tuned. 9/n