Resveratrol Downmodulates Neutrophil Extracellular Trap (NET) Generation by Neutrophils in Patients with Severe COVID-19
Milena M. de Souza Andrade,
Vinicius N. C. Leal,
Iara G. Fernandes,
Sarah C. Gozzi-Silva,
Danielle R. Beserra,
Emily A. Oliveira,
Franciane M. E. Teixeira,
Tatiana M. Yendo,
Maria da Glória T. Sousa,
Walcy R. Teodoro,
Luana de M. Oliveira,
Ricardo W. Alberca,
Valéria Aoki,
Alberto J. S. Duarte,
Maria N. Sato
Affiliations
Milena M. de Souza Andrade
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Vinicius N. C. Leal
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
Iara G. Fernandes
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Sarah C. Gozzi-Silva
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Danielle R. Beserra
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Emily A. Oliveira
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Franciane M. E. Teixeira
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Tatiana M. Yendo
Hospital das Clínicas of the University of São Paulo (HCFMUSP), University of São Paulo, São Paulo 05403-000, Brazil
Maria da Glória T. Sousa
Laboratory of Mycology, LIM-53, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Walcy R. Teodoro
Laboratory of Extracellular Matrix-Rheumatology, LIM-17, Department of Medical Clinic, University of São Paulo Medical School, São Paulo 01246-903, Brazil
Luana de M. Oliveira
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Ricardo W. Alberca
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
Valéria Aoki
Hospital das Clínicas of the University of São Paulo (HCFMUSP), University of São Paulo, São Paulo 05403-000, Brazil
Alberto J. S. Duarte
Hospital das Clínicas of the University of São Paulo (HCFMUSP), University of São Paulo, São Paulo 05403-000, Brazil
Maria N. Sato
Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo 05403-000, Brazil
The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clínicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes.
