Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions

Mathew, Divij; Giles, Josephine R.; Baxter, Amy E.; Greenplate, Allison R.; Wu, Jennifer E.; Alanio, Cécile; Oldridge, Derek A.; 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.; Hensley, Scott E.; Apostolidis, Sokratis; Huang, Alexander C.; Vella, Laura A.; Betts, Michael R.; Meyer, Nuala J.; Wherry, E. John

COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ~200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >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 therapeutics and vaccines.