TY - JOUR
T1 - Aberrant neutrophil degranulation in hospitalized patients with COVID-19 partially remains for 6 months
AU - Hafkamp, Florianne M. J.
AU - Taanman-Kueter, Esther W. M.
AU - van Capel, Toni M. M.
AU - Wynberg, Elke
AU - van Willigen, Hugo D. G.
AU - Verveen, Anouk
AU - Kootstra, Neeltje A.
AU - Nieuwkerk, Pythia
AU - de Jong, Menno D.
AU - de Bree, Godelieve J.
AU - Prins, Maria
AU - RECoVERED Study Group
AU - Hazenberg, Mette D.
AU - Groot Kormelink, Tom
AU - de Jong, Esther C.
N1 - Funding Information: This work was supported by Amsterdam UMC, University of Amsterdam, and by the Netherlands Organization for Health Research and Development (ZonMw) (RECoVERED, grant agreement numbers 10150062010002 to M.D. de Jong and 10430072110003 to G.J. de Bree) and the Public Health Service of Amsterdam (Research & Development grant number 21‐14 to M. Prins). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Publisher Copyright: © 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
PY - 2023
Y1 - 2023
N2 - Neutrophils are important players in COVID-19, contributing to tissue damage by release of inflammatory mediators, including 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 nonhospitalized and 35 hospitalized patients) compared with 17 healthy donors (HDs). We assessed phenotype, degranulation, CXCL8 (IL-8) release, and ROS generation within 8 days, at one or 6 month(s) after COVID-19 diagnosis. For degranulation and ROS production, we stimulated neutrophils, either with ssRNA and TNF or granulocyte-macrophage colony-stimulating factor and N-Formylmethionyl-leucyl-phenylalanine. 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 nonhospitalized 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 6 months. These findings show that patients hospitalized due to COVID-19, but not nonhospitalized patients, demonstrated an aberrant neutrophil phenotype, degranulation, CXCL8 release, and ROS generation that partially persists up to 6 months after infection.
AB - Neutrophils are important players in COVID-19, contributing to tissue damage by release of inflammatory mediators, including 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 nonhospitalized and 35 hospitalized patients) compared with 17 healthy donors (HDs). We assessed phenotype, degranulation, CXCL8 (IL-8) release, and ROS generation within 8 days, at one or 6 month(s) after COVID-19 diagnosis. For degranulation and ROS production, we stimulated neutrophils, either with ssRNA and TNF or granulocyte-macrophage colony-stimulating factor and N-Formylmethionyl-leucyl-phenylalanine. 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 nonhospitalized 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 6 months. These findings show that patients hospitalized due to COVID-19, but not nonhospitalized patients, demonstrated an aberrant neutrophil phenotype, degranulation, CXCL8 release, and ROS generation that partially persists up to 6 months after infection.
KW - COVID-19
KW - CXCL8
KW - Degranulation
KW - Neutrophils
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=85175460654&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/eji.202350404
DO - https://doi.org/10.1002/eji.202350404
M3 - Article
C2 - 37853954
SN - 0014-2980
JO - European journal of immunology
JF - European journal of immunology
ER -