Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications

Mathew, Divij; Giles, Josephine R.; Baxter, Amy E.; Oldridge, Derek A.; Greenplate, Allison R.; Wu, Jennifer E.; Alanio, Cécile; Kuri-Cervantes, Leticia; Pampena, M. Betina; D’Andrea, Kurt; Manne, Sasikanth; Chen, Zeyu; Huang, Yinghui Jane; Reilly, John P.; Weisman, Ariel R.; Ittner, Caroline A. G.; Kuthuru, Oliva; Dougherty, Jeanette; Nzingha, Kito; Han, Nicholas; Kim, Justin; Pattekar, Ajinkya; Goodwin, Eileen C.; Anderson, Elizabeth M.; Weirick, Madison E.; Gouma, Sigrid; Arevalo, Claudia P.; Bolton, Marcus J.; Chen, Fang; Lacey, Simon F.; Ramage, Holly; Cherry, Sara; Hensley, Scott E.; Apostolidis, Sokratis A.; Huang, Alexander C.; Vella, Laura A.; Betts, Michael R.; Meyer, Nuala J.; Wherry, E. John

COVID-19 is currently a global pandemic, but human immune responses to the virus remain poorly understood. We analyzed 125 COVID-19 patients, and compared recovered to healthy individuals using high dimensional cytometry. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three “immunotypes” associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.