Viral and Immune Factors Associated With COVID-19 Outcome in the C3PO Trial of Convalescent Plasma

We examined innate and antibody responses in C3PO clinical trial participants of coronavirus disease 2019 (COVID-19) convalescent plasma to identify predictors of disease progression. We found severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viremia in 64% of participants at enrollment, and we could also quantify viremia in approximately half of those samples using an RT-PCR assay. Viremia was associated with increased risk of disease progression (OR, 3.0; 95% CI, 1.7-5.0). Participants with viremia at baseline had lower SARS-CoV-2 binding antibody levels and higher proinflammatory cytokine levels, including IP-10 (CXCL10), TNF-α, calprotectin, and CRP. Disease progression correlated with extracellular vesicle levels from multiple cell types in the convalescent but not acute phase of the disease. Male sex predicted worse disease outcome and was associated with higher baseline levels of several proinflammatory cytokines. Viremia's strong predictive value for disease progression argues for further study of its use to predict which patients with COVID-19 might require more intensive therapy or monitoring.