A Poor and Delayed Anti-SARS-CoV2 IgG Response is Associated to Severe COVID-19 in Children

Background: Most children and youth develop mild or asymptomatic disease during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, a very small number of patients suffer severe Coronavirus induced disease 2019 (COVID-19). The reasons underlying these different outcomes remain unknown. Methods: We analyzed three different cohorts: children with acute infection (n=550), convalescent children (n=138), and MIS-C (multisystem inflammatory syndrome in children, n=42). IgG and IgM antibodies to the spike protein of SARS-CoV-2, serum-neutralizing activity, plasma cytokine levels, and the frequency of circulating Follicular T helper cells (cTfh) and plasmablasts were analyzed by conventional methods. Findings: Fifty-eight percent of the children in the acute phase of infection had no detectable antibodies at the time of sampling while a seronegative status was found in 25% and 12% of convalescent and MIS-C children, respectively. When children in the acute phase of the infection were stratified according disease severity, we found that contrasting with the response of children with asymptomatic, mild and moderate disease, children with severe COVID-19 did not develop any detectable response. A defective antibody response was also observed in the convalescent cohort for children with severe disease at the time of admission. This poor antibody response was associated to both, a low frequency of cTfh and a high plasma concentration of inflammatory cytokines. Interpretation: A weak and delayed kinetic of antibody response to SARS-CoV-2 together with a systemic pro-inflammatory profile characterize to pediatric severe COVID-19. Funding Information: National Agency for Scientific and Technological Promotion from Argentina (IP-COVID-19-0277 and PMO-BID-PICT2018-2548). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: This study was conducted in accordance with the Declaration of Helsinki. The Institutional Review Board at institutions participants reviewed and approved the sample collection and the overall study (Hospital General de Ninos Pedro de Elizalde protocol reference 1226/20, Hospital Universitario Austral protocol reference 2147/2020 and Hospital General de Agudos Dr. J. A Fernandez protocol reference 1720/20). Parents or legal guardians from children under 8 years provided written, informed consent. Children older than 8 years old provided written, informed assent and their parents or legal guardians also provided written, informed consent.