Abstract
Despite a rapidly growing body of literature on COVID-19, our understanding of the immune correlates of disease severity, course and outcome remains poor. Using mass cytometry, we assessed the immune landscape in longitudinal whole blood specimens from 59 patients presenting with acute COVID-19, and classified based on maximal disease severity. Hospitalized patients negative for SARS-CoV-2 were used as controls. We found that the immune landscape in COVID-19 forms three dominant clusters, which correlate with disease severity. Longitudinal analysis identified a pattern of productive innate and adaptive immune responses in individuals who have a moderate disease course, whereas those with severe disease have features suggestive of a protracted and dysregulated immune response. Further, we identified coordinate immune alterations accompanying clinical improvement and decline that were also seen in patients who received IL-6 pathway blockade. The hospitalized COVID-19 negative cohort allowed us to identify immune alterations that were shared between severe COVID-19 and other critically ill patients. Collectively, our findings indicate that selection of immune interventions should be based in part on disease presentation and early disease trajectory due to the profound differences in the immune response in those with mild to moderate disease and those with the most severe disease.
Competing Interest Statement
J.H.B is President of the Benaroya Research Institute at Virginia Mason, a consultant for Bristol-Myers Squibb and has past and current research projects sponsored by Amgen, Bristol-Myers Squib, Janssen, Novo Nordisk, and Pfizer. J.H.B also has a patent on methods of generating antigen-specific CD4+CD25+ regulatory T cells. All other authors have declared no conflict of interest exists.
Footnotes
Conflict of interest statement J.H.B is President of the Benaroya Research Institute at Virginia Mason, a consultant for Bristol-Myers Squibb and has past and current research projects sponsored by Amgen, Bristol-Myers Squib, Janssen, Novo Nordisk, and Pfizer. J.H.B also has a patent on methods of generating antigen-specific CD4+CD25+ regulatory T cells. All other authors have declared no conflict of interest exists.
Updated to improve legibility of labels for heatmaps in Figures 2A and 4E. Also added p=value to Figure 7D neutrophil plot