Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Autor:	Carmona-Rivera C; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA., Zhang Y; Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA., Dobbs K; LCIM, NIH, Bethesda, MD,USA., Markowitz TE; Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD.; Axle Informatics, Bethesda, MD, USA., Dalgard CL; Department of Anatomy, Physiology & Genetics, School of Medicine, Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD and The American Genome Center, USUHS, Bethesda, MD, USA., Oler AJ; Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD., Claybaugh DR; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA., Draper D; LCIM, NIH, Bethesda, MD,USA., Truong M; LCIM, NIH, Bethesda, MD,USA., Delmonte OM; LCIM, NIH, Bethesda, MD,USA., Licciardi F; Department of Public Health and Pediatric Sciences, 'Regina Margherita' Children's Hospital, University of Turin, Turin, Italy., Ramenghi U; Department of Public Health and Pediatric Sciences, 'Regina Margherita' Children's Hospital, University of Turin, Turin, Italy., Crescenzio N; Pediatric Hematology, 'Regina Margherita' Children Hospital, University of Turin, Turin, Italy., Imberti L; Centro di Ricerca Emato-oncologica AIL (CREA), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy., Sottini A; Centro di Ricerca Emato-oncologica AIL (CREA), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy., Quaresima V; Centro di Ricerca Emato-oncologica AIL (CREA), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy., Fiorini C; Centro di Ricerca Emato-oncologica AIL (CREA), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy., Discepolo V; Department of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy., Lo Vecchio A; Department of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy., Guarino A; Department of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy., Pierri L; Department of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy., Catzola A; Department of Translational Medical Sciences, Pediatric Section, University of Naples Federico II, Naples, Italy., Biondi A; Department of Pediatrics, University of Milano-Bicocca, European Reference Network (ERN) PaedCan, EuroBloodNet, MetabERN, Fondazione MBBM/Ospedale San Gerardo, Monza, Italy., Bonfanti P; Department of Infectious Diseases, San Gerardo Hospital-University of Milano-Bicocca, Monza, Italy., Poli Harlowe MC; Programa de Inmunogenética e Inmunología Traslacional, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile.; Hospital Roberto del Rio, Santiago, Chile., Espinosa Y; Hospital Roberto del Rio, Santiago, Chile., Astudillo C; Hospital Roberto del Rio, Santiago, Chile., Rey-Jurado E; Programa de Inmunogenética e Inmunología Traslacional, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile., Vial C; Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Programa Hantavirus, Instituto de Ciencias e Innovación en Medicina, Santiago, Chile., de la Cruz J; Programa de Inmunogenética e Inmunología Traslacional, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile., Gonzalez R; Pediatric Intensive Care Unit, Hospital Exequiel Gonzalez Cortés, Santiago, Chile., Pinera C; Infectious Diseases Unit, Hospital Dr. Exequiel González Cortés, Región Metropolitana, Chile.; Faculty of Medicine, Universidad de Chile, Santiago, Chile., Mays JW; National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA., Ng A; Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Platt A; Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, and Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA., Drolet B; Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Moon J; Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Cowen EW; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD., Kenney H; LCIM, NIH, Bethesda, MD,USA., Weber SE; LCIM, NIH, Bethesda, MD,USA., Castagnoli R; LCIM, NIH, Bethesda, MD,USA., Magliocco M; Dermatology Branch, NIAMS, NIH, Bethesda, MD, USA2., Stack MA; Dermatology Branch, NIAMS, NIH, Bethesda, MD, USA2., Montealegre G; Division of Clinical Research, NIAID, NIH, Bethesda, MD., Barron K; Division of Clinical Research, NIAID, NIH, Bethesda, MD., Hewitt SM; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA., Arkin LM; Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Chertow DS; Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, and Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA., Su HC; Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA., Notarangelo LD; LCIM, NIH, Bethesda, MD,USA., Kaplan MJ; Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2022 Mar 03. Date of Electronic Publication: 2022 Mar 03.
DOI:	10.1101/2022.02.24.22271475
Abstrakt:	Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL), otherwise known as "COVID toes", remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients. Summary: NET formation and degradation are dysregulated in pediatric and symptomatic adult patients with various complications of COVID-19, in association with disease severity. NET degradation impairments are multifactorial and associated with natural inhibitors of DNase 1, G-actin and anti-DNase1L3 and anti-NET antibodies. Infection with the Omicron variant is associated with decreased levels of NETs when compared to other SARS-CoV-2 strains.
Databáze:	MEDLINE
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