Humoral signatures of protective and pathological SARS-CoV-2 infection in children

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS...

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Veröffentlicht in:	Nature medicine Jg. 27; H. 3; S. 454 - 462
Hauptverfasser:	Bartsch, Yannic C., Wang, Chuangqi, Zohar, Tomer, Fischinger, Stephanie, Atyeo, Caroline, Burke, John S., Kang, Jaewon, Edlow, Andrea G., Fasano, Alessio, Baden, Lindsey R., Nilles, Eric J., Woolley, Ann E., Karlson, Elizabeth W., Hopke, Alex R., Irimia, Daniel, Fischer, Eric S., Ryan, Edward T., Charles, Richelle C., Julg, Boris D., Lauffenburger, Douglas A., Yonker, Lael M., Alter, Galit
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York Nature Publishing Group US 01.03.2021 Nature Publishing Group
Schlagworte:	631/250/2152/2153 631/250/2152/2153/1291 631/250/255 631/250/255/2514 692/420 Adolescent Adult Adults Age of Onset Aged Antibodies Antibodies, Neutralizing - analysis Antibodies, Neutralizing - blood Antibodies, Viral - analysis Antibodies, Viral - blood Asymptomatic Infections Biomedical and Life Sciences Biomedicine Cancer Research Carrier State - blood Carrier State - epidemiology Child Child, Preschool Children Cohort Studies Complications and side effects Coronaviridae Coronaviruses COVID-19 COVID-19 - blood COVID-19 - epidemiology COVID-19 - pathology Demographic aspects Epidemics Female Genetic aspects Humans Immune response Immunity - physiology Immunoglobulin A Immunoglobulin A - blood Immunoglobulin G Immunoglobulin G - blood Infant Infant, Newborn Infectious Diseases Inflammation Leukocytes (neutrophilic) Male Metabolic Diseases Middle Aged Molecular Medicine Monocytes Multisystem inflammatory syndrome in children Neurosciences Pandemics Pathogenesis Phenotypes Respiratory diseases Respiratory failure SARS-CoV-2 - immunology Serology Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Systemic Inflammatory Response Syndrome - blood Systemic Inflammatory Response Syndrome - epidemiology Viral diseases Young Adult United States
ISSN:	1078-8956, 1546-170X, 1546-170X
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Zusammenfassung:	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2. A study of multisystem inflammatory syndrome in children (MIS-C) shows maintenance of elevated levels of monocyte-activating pathogen-specific IgG not seen in children infected with SARS-CoV-2 who do not develop MIS-C.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Author contribution YCB, LMY and GA analyzed and interpreted the data. YCB, TZ, SF CA, JB, JK, ARH and DI performed experiments. CW and DAL performed the computational analysis. AGE, AF, LRB, EJN, LRB, AEW, EWB, ETR, RC, BDJ and LMY collected the samples and supervised and managed the clinical data. ESF produced SARS-CoV-2 and human coronavirus antigens. LMY and GA supervised the project. YCB and GA drafted the manuscript. All authors critically reviewed the manuscript.
ISSN:	1078-8956 1546-170X 1546-170X
DOI:	10.1038/s41591-021-01263-3