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

Divij Mathew(Translational Therapeutics (United States)), Josephine R. Giles(Parker Institute for Cancer Immunotherapy), Amy E. Baxter(Translational Therapeutics (United States)), Allison R. Greenplate(Translational Therapeutics (United States)), Jennifer E. Wu(Parker Institute for Cancer Immunotherapy), Cécile Alanio(Parker Institute for Cancer Immunotherapy), Derek A. Oldridge(University of Pennsylvania), Leticia Kuri-Cervantes(University of Pennsylvania), M. Betina Pampena(University of Pennsylvania), Kurt D’Andrea(University of Pennsylvania), Sasikanth Manne(Translational Therapeutics (United States)), Zeyu Chen(Translational Therapeutics (United States)), Yinghui Huang(Translational Therapeutics (United States)), John P. Reilly(University of Pennsylvania), Ariel R. Weisman(University of Pennsylvania), C.A.G. Ittner(University of Pennsylvania), Oliva Kuthuru(Translational Therapeutics (United States)), Jeanette Dougherty(Translational Therapeutics (United States)), Kito Nzingha(Translational Therapeutics (United States)), Nicholas Han(Translational Therapeutics (United States)), Justin Kim(Translational Therapeutics (United States)), Ajinkya Pattekar(University of Pennsylvania), Eileen C. Goodwin(University of Pennsylvania), Elizabeth M. Anderson(University of Pennsylvania), Madison E. Weirick(University of Pennsylvania), Sigrid Gouma(University of Pennsylvania), Claudia P. Arevalo(University of Pennsylvania), Marcus J. Bolton(University of Pennsylvania), Chen Fang(Parker Institute for Cancer Immunotherapy), Simon F. Lacey(Parker Institute for Cancer Immunotherapy), Scott E. Hensley(University of Pennsylvania), Sokratis A. Apostolidis(University of Pennsylvania), Alexander C. Huang(University of Pennsylvania), Laura A. Vella(Children's Hospital of Philadelphia), The UPenn COVID Processing Unit(University of Pennsylvania), Michael R. Betts(University of Pennsylvania), Nuala J. Meyer(Parker Institute for Cancer Immunotherapy), E. John Wherry(Parker Institute for Cancer Immunotherapy)
bioRxiv (Cold Spring Harbor Laboratory)
May 23, 2020
Cited by 115Open Access
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Abstract

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.


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