The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity

BACKGROUND. Despite a rapidly growing body of literature on coronavirus disease 2 019 (COVID-19), our understanding of the immune correlates of disease severity, course, and outcome remains poor. METHODS. 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. RESULTS. We found that the immune landscape in COVID-19 formed 3 dominant clusters, which correlated with disease severity. Longitudinal analysis identified a pattern of productive innate and adaptive immune responses in individuals who had a moderate disease course, whereas those with severe disease had 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. CONCLUSION. 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.

Automated summary

Despite the rapidly growing literature on COVID-19, our understanding of the immune correlates of disease severity remains poor. Using mass cytometry, we found that there are 3 dominant immune clusters in COVID-19 patients, correlated with disease severity. Immune responses differ significantly between mild to moderate disease and severe disease, indicating that immune interventions should be selected based on disease presentation and early trajectory.