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Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients by Thomas J. LaSalle; Anna L.K. Gonye; Samuel S. Freeman; Paulina Kaplonek; Irena Gushterova; Kyle R. Kays; Kasidet Manakongtreecheep; Jessica Tantivit; Maricarmen Rojas-Lopez; Brian C. Russo; Nihaarika Sharma; Molly F. Thomas; Kendall M. Lavin-Parsons; Brendan M. Lilly; Brenna N. Mckaig; Nicole C. Charland; Hargun K. Khanna; Carl L. Lodenstein; Justin D. Margolin; Emily M. Blaum; Paola B. Lirofonis; Or-Yam Revach; Arnav Mehta; Abraham Sonny; Roby P. Bhattacharyya; Blair Alden Parry; Marcia B. Goldberg; Galit Alter; Michael R. Filbin; Alexandra-Chloé Villani; Nir Hacohen; Moshe Sade-Feldman is a Medicine article available to read on EtoBox.

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## Summary Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19^+^ patients and 86 controls and perform bulk RNA sequencing of enriched neutrophils, plasma proteomics, and high-throughput antibody profiling to investigate relationships between neutrophil states and disease severity. We identify dynamic switches between six distinct neutrophil subtypes. At days 3 and 7 post-hospitalization, patients with severe disease display a granulocytic myeloid-derived suppressor cell-like gene expression signature, while patients with resolving disease show a neutrophil progenitor-like signature. Humoral responses are identified as potential drivers of neutrophil effector functions, with elevated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G1 (IgG1)-to-IgA1 ratios in plasma of severe patients who survived. __In vitro__ experiments confirm that while patient-derived IgG antibodies induce phagocytosis in healthy donor neutrophils, IgA antibodies predominantly induce neutrophil cell death. Overall, our study demonstrates

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Author

Thomas J. LaSalle; Anna L.K. Gonye; Samuel S. Freeman; Paulina Kaplonek; Irena Gushterova; Kyle R. Kays; Kasidet Manakongtreecheep; Jessica Tantivit; Maricarmen Rojas-Lopez; Brian C. Russo; Nihaarika Sharma; Molly F. Thomas; Kendall M. Lavin-Parsons; Brendan M. Lilly; Brenna N. Mckaig; Nicole C. Charland; Hargun K. Khanna; Carl L. Lodenstein; Justin D. Margolin; Emily M. Blaum; Paola B. Lirofonis; Or-Yam Revach; Arnav Mehta; Abraham Sonny; Roby P. Bhattacharyya; Blair Alden Parry; Marcia B. Goldberg; Galit Alter; Michael R. Filbin; Alexandra-Chloé Villani; Nir Hacohen; Moshe Sade-Feldman

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Medicine (Health Sciences)