Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications
Divij Mathew, Josephine R. Giles, Amy E. Baxter, Derek A. Oldridge, Allison R. Greenplate, Jennifer E. Wu, Cécile Alanio, Leticia Kuri-Cervantes, M. Betina Pampena, Kurt D’Andrea, Sasikanth Manne, Zeyu Chen, Yinghui Huang, John P. Reilly, Ariel R. Weisman, C.A.G. Ittner, Oliva Kuthuru, Jeanette Dougherty, Kito Nzingha, Nicholas Han, Justin Kim, Ajinkya Pattekar, Eileen C. Goodwin, Elizabeth M. Anderson, Madison E. Weirick, Sigrid Gouma, Claudia P. Arevalo, Marcus J. Bolton, Chen Fang, Simon F. Lacey, Holly Ramage, Sara Cherry, Scott E. Hensley, Sokratis A. Apostolidis, Alexander C. Huang, Laura A. Vella, The UPenn COVID Processing Unit, Michael R. Betts, Nuala J. Meyer, E. John Wherry, Zahidul Alam, Mary M. Addison, Katelyn T. Byrne, Aditi Chandra, Hélène C. Descamps, Yaroslav Kaminskiy, Jacob T. Hamilton, Julia Han Noll, Dalia K. Omran, Eric Perkey, Elizabeth M. Prager, Dana Pueschl, Jennifer Shah, Jake Shilan, Ashley Vanderbeck
Abstract
Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 patients and compare them with recovered and healthy individuals. 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 with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our 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.