Article
Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19
Fecha
2022Registro en:
Carmona-Rivera C, Zhang Y, Dobbs K, Markowitz TE, Dalgard CL, Oler AJ, Claybaugh DR, Draper D, Truong M, Delmonte OM, Licciardi F, Ramenghi U, Crescenzio N, Imberti L, Sottini A, Quaresima V, Fiorini C, Discepolo V, Lo Vecchio A, Guarino A, Pierri L, Catzola A, Biondi A, Bonfanti P, Poli Harlowe MC, Espinosa Y, Astudillo C, Rey-Jurado E, Vial C, de la Cruz J, Gonzalez R, Pinera C, Mays JW, Ng A, Platt A; NIH COVID Autopsy Consortium; COVID STORM Clinicians; Drolet B, Moon J, Cowen EW, Kenney H, Weber SE, Castagnoli R, Magliocco M, Stack MA, Montealegre G, Barron K, Fink DL, Kuhns DB, Hewitt SM, Arkin LM, Chertow DS, Su HC, Notarangelo LD, Kaplan MJ. Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19. JCI Insight. 2022 Aug 22;7(16):e160332. doi: 10.1172/jci.insight.160332
Autor
Carmona, Carmelo
Zhang, Yu
Dobbs, Kerry
Markowitz, Tovah
Dalgard, Clifton
Oler, Andrew
Claybaugh, Dillon
Draper, Deborah
Truong, Meng
Delmonte, Ottavia
Licciardi, Francesco
Ramenghi, Ugo
Crescenzio, Nicoletta
Imberti, Luisa
Sottini, Alessandra
Quaresima, Virginia
Fiorini, Chiara
Discepolo, Valentina
Lo Vecchio, Andrea
Guarino, Alfredo
Pierri, Luca
Catzola, Andrea
Biondi, Andrea
Bonfanti, Paolo
Poli, Cecilia
Espinosa, Yasmin
Astudillo, Camila
Rey, Emma
Vial, Cecilia
De la Cruz, Javiera
González, Ricardo
Pinera, Cecilia
Mays, Jacqueline
Ng, Ashley
Platt, Andrew
NIH COVID Autopsy Consortium
COVID STORM Clinicians
Drolet, Beth
Moon, John
Cowen, Edward
Kenney, Heather
Weber, Sarah
Castagnoli, Riccardo
Magliocco, Mary
Stack, Michael
Montealegre, Gina
Barron, Karyl
Fink, Danielle
Kuhns, Douglas
Hewitt, Stephen
Arkin, Lisa
Chertow, Daniel
Su, Helen
Notarangelo, Luigi
Kaplan, Mariana
Institución
Resumen
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 multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, in CLLs, 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 after 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 NET levels when compared with 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.