Peripheral blood cytokines during early and post-acute stages of SARS-CoV-2 infection are associated with disease severity and long-term symptoms.

Background: U.S. Veterans experience a high burden of COVID-19; characterizing immune responses associated with COVID-19 outcomes could help improve treatment. Changes in peripheral blood cytokines over time may predict both acute outcomes and long COVID symptoms. Methods: Cytokine concentrations were quantified from peripheral blood collected 0-7 days (early) and 14-42 days (post-acute) after enrollment from SARS-CoV-2 positive participants in the EPIC Results: Early HGF, IL-18, IL-1RA, IP-10, and VEGF-A and post-acute MIP-1α and VEGF-A concentrations trended positively with increasing COVID-19 severity (q-values < 0.05, Jonckheere-Terpstra trend test). Increases in EGF, MIP-1β, and RANTES concentration and decreases in MIP-1α concentration over time were associated with mild rather than moderate or severe disease. Increases in MIP-1β and RANTES concentration and decreases in Eotaxin concentration over time were associated with the absence of long-term symptoms. Conclusions: Worse COVID-19 severity by 30 days was associated with higher early and post-acute period cytokine concentrations. Participants with long-term symptoms did not see resolution of cytokine responses over time.