TY - JOUR AU - Carmona-Rivera, Carmelo AU - Zhang, Yu AU - Dobbs, Kerry AU - Markowitz, Tovah E. AU - Dalgard, Clifton L. AU - Oler, Andrew J. AU - Claybaugh, Dillon R. AU - Draper, Deborah AU - Truong, Meng AU - Delmonte, Ottavia M. AU - Licciardi, Francesco AU - Ramenghi, Ugo AU - Crescenzio, Nicoletta AU - Imberti, Luisa AU - Sottini, Alessandra AU - Quaresima, Virginia AU - Fiorini, Chiara AU - Discepolo, Valentina AU - Lo Vecchio, Andrea AU - Guarino, Alfredo AU - Pierri, Luca AU - Catzola, Andrea AU - Biondi, Andrea AU - Bonfanti, Paolo AU - Poli Harlowe, Maria C. AU - Espinosa, Yasmin AU - Astudillo, Camila AU - Rey-Jurado, Emma AU - Vial, Cecilia AU - de la Cruz, Javiera AU - Gonzalez, Ricardo AU - Pinera, Cecilia AU - Mays, Jacqueline W. AU - Ng, Ashley AU - Platt, Andrew AU - , AU - , AU - Drolet, Beth AU - Moon, John AU - Cowen, Edward W. AU - Kenney, Heather AU - Weber, Sarah E. AU - Castagnoli, Riccardo AU - Magliocco, Mary AU - Stack, Michael A. AU - Montealegre, Gina AU - Barron, Karyl AU - Fink, Danielle L. AU - Kuhns, Douglas B. AU - Hewitt, Stephen M. AU - Arkin, Lisa M. AU - Chertow, Daniel S. AU - Su, Helen C. AU - Notarangelo, Luigi D. AU - Kaplan, Mariana J. T1 - Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19 PY - 2022/10/05/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.160332 VL - 7 IS - 16 UR - https://doi.org/10.1172/jci.insight.160332 PB - The American Society for Clinical Investigation ER -