Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection
By
Leticia Kuri-Cervantes,
M. Betina Pampena,
Wenzhao Meng,
Aaron M Rosenfeld,
Caroline A.G. Ittner,
Ariel R Weisman,
Roseline Agyekum,
Divij Mathew,
Amy E. Baxter,
Laura Vella,
Oliva Kuthuru,
Sokratis A Apostolidis,
Luanne Bershaw,
Jeannete Dougherty,
Allison R. Greenplate,
Ajinkya Pattekar,
Justin Kim,
Nicholas Han,
Sigrid Gouma,
Madison E. Weirick,
Claudia P Arevalo,
Marcus J Bolton,
Eileen C. Goodwin,
Elizabeth M Anderson,
Scott E. Hensley,
Tiffanie K. Jones,
Nilam S. Mangalmurti,
Eline T Luning Prak,
E John Wherry,
Nuala J. Meyer,
Michael R. Betts
Posted 18 May 2020
bioRxiv DOI: 10.1101/2020.05.18.101717
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 broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2-specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation. ### Competing Interest Statement NJM reports funding to her institution from Athersys, Inc, Biomarck Inc, and the Marcus Foundation for research unrelated to the work under consideration. She has no other conflicts of interest. EJW is a member of the Parker Institute for Cancer Immunotherapy. EJW has consulting agreements with and/or is on the scientific advisory board for Merck, Roche, Pieris, Elstar, and Surface Oncology. EJW is a founder of Surface Oncology and Arsenal Biosciences. EJW has a patent licensing agreement on the PD-1 pathway with Roche/Genentech. SEH has received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck for work unrelated to this report. ETLP is currently receiving funding from Janssen Pharmaceuticals, and is part of a scientific advisory panel for Roche Diagnostics Corporation for work unrelated to this publication
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