|
|||||
|
|
Aberrant neutrophil degranulation in hospitalized patients with COVID-19 partially remains for 6 months |
|
| Authors: | Florianne M.J. Hafkamp Esther W. M. Taanman-Kueter Toni M. M. van Capel Elke Wynberg Hugo D. G. van Willigen Anouk Verveen Neeltje A. Kootstra Pythia Nieuwkerk Menno D. de Jong Godelieve J. de Bree Maria Prins RECoVERED study group Mette D. Hazenberg Tom Groot Kormelink Esther C. de Jong |
| Affiliation: | 1. Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands;2. Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands Department of Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands;3. Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands Department of Medical Microbiology & Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands Department of Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands;4. Department of Medical Psychology, Amsterdam UMC, Amsterdam Public Health Research Institute, University of Amsterdam, Amsterdam, the Netherlands;5. Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands Department of Medical Microbiology & Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands;6. Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands Department of Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands;7. Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands Listed under acknowledgements section.;8. Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands Department of Hematopoiesis, Sanquin Research, Amsterdam, the Netherlands;9. Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands |
| Abstract: | 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. |
| Keywords: | COVID-19 CXCL8 Degranulation Neutrophils ROS |