Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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LaSalle Thomas J, Gonye Anna L K, Freeman Samuel S, Kaplonek Paulina, Gushterova Irena, Kays Kyle R, Manakongtreecheep Kasidet, Tantivit Jessica, Rojas-Lopez Maricarmen, Russo Brian C, Sharma Nihaarika, Thomas Molly F, Lavin-Parsons Kendall M, Lilly Brendan M, Mckaig Brenna N, Charland Nicole C, Khanna Hargun K, Lodenstein Carl L, Margolin Justin D, Blaum Emily M, Lirofonis Paola B, Revach Or-Yam, Mehta Arnav, Sonny Abraham, Bhattacharyya Roby P, Parry Blair Alden, Goldberg Marcia B, Alter Galit, Filbin Michael R, Villani Alexandra-Chloé, Hacohen Nir, Sade-Feldman Moshe
Аннотация
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 a dysregulated myelopoietic response in severe COVID-19 and a potential role for IgA-dominant responses contributing to mortality.