Comprehensive mapping of immune perturbations associated with severe COVID-19

Kuri-Cervantes, Leticia; Pampena, M. Betina; Meng, Wenzhao; Rosenfeld, Aaron M.; Ittner, Caroline A.G.; Weisman, Ariel R.; Agyekum, Roseline S.; Mathew, Divij; Baxter, Amy E.; Vella, Laura A.; Kuthuru, Oliva; Apostolidis, Sokratis A.; Bershaw, Luanne; Dougherty, Jeanette; Greenplate, Allison R.; Pattekar, Ajinkya; Kim, Justin; Han, Nicholas; Gouma, Sigrid; Weirick, Madison E.; Arevalo, Claudia P.; Bolton, Marcus J.; Goodwin, Eileen C.; Anderson, Elizabeth M.; Hensley, Scott E.; Jones, Tiffanie K.; Mangalmurti, Nilam S.; Luning Prak, Eline T.; Wherry, E. John; Meyer, Nuala J.; Betts, Michael R.

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.