Aberrant neutrophil degranulation in hospitalized patients with COVID‐19 partially remains for 6 months

Abstract

Neutrophils are important players in COVID‐19, contributing to tissue damage by release of inflammatory mediators, including reactive oxygen species (ROS) and neutrophil elastase. Longitudinal studies on the effects of COVID‐19 on neutrophil phenotype and function are scarce. Here, we longitudinally investigated the phenotype and degranulation of neutrophils in COVID‐19 patients (28 non‐hospitalized and 35 hospitalized patients) compared to 17 healthy donors (HDs). We assessed phenotype, degranulation, CXCL8 (IL‐8) release and ROS generation within 8 days, at one or six month(s) after COVID‐19 diagnosis. For degranulation and ROS production, we stimulated neutrophils, either with single‐stranded RNA (ssRNA) and tumor necrosis factor (TNF) or granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and N‐Formylmethionyl‐leucyl‐phenylalanine (fMLP). During active COVID‐19, neutrophils from hospitalized patients were more immature than from HDs and were impaired in degranulation and ROS generation, while neutrophils from non‐hospitalized patients only demonstrated reduced CD66b+ granule release and ROS production. Baseline CD63 expression, indicative of primary granule release, and CXCL8 production by neutrophils from hospitalized patients were elevated for up to six months. These findings show that patients hospitalized due to COVID‐19, but not non‐hospitalized patients, demonstrated an aberrant neutrophil phenotype, degranulation, CXCL8 release and ROS generation that partially persists up to six months after infection.This article is protected by copyright. All rights reserved