Infants and young children generate more durable antibody responses to SARS-CoV-2 infection than adults

Since the emergence of SARS-CoV-2, research has shown that adult patients mount broad and durable immune responses to infection. However, response to infection remains poorly studied in infants/young children. In this study, we evaluated humoral responses to SARS-CoV-2 in 23 infants/young children before and after infection. We found that antibody responses to SARS-CoV-2 spike antigens peaked approximately 30 days after infection and were maintained up to 500 days with little apparent decay. While the magnitude of humoral responses was similar to an adult cohort recovered from mild/moderate COVID-19, both binding and neutralization titers to WT SARS-CoV-2 were more durable in infants/young children, with Spike and RBD IgG antibody half-life nearly 4X as long as in adults. The functional breadth of adult and infant/young children SARS-CoV-2 responses were comparable, with similar reactivity against panel of recent and previously circulating viral variants. Notably, IgG subtype analysis revealed that while IgG1 formed the majority of both adults' and infants/young children's response, IgG3 was more common in adults and IgG2 in infants/young children. These findings raise important questions regarding differential regulation of humoral immunity in infants/young children and adults and could have broad implications for the timing of vaccination and booster strategies in this age group. ### Competing Interest Statement MSS has served as an advisor for Ocugen and Moderna. E.J.A. has consulted for Pfizer, Sanofi Pasteur, Janssen, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sonfi-Pasteur, Janssen, and Micron. He also serves on data and safety monitoring boards for Kentucky BioProcessing, Inc., and Sanofi Pasteur. His institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. M.A.S. received funding from CDC, Pfizer, Merck and Cepheid to study immune response to respiratory virus infections and vaccinations. ### Funding Statement This work was supported in part by grants U01AI144673-02, 3U19AI057266-17S2, and U54CA260563 from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and by the Oliver S. and Jennie R. Donaldson Charitable Trust, Emory Executive Vice President for Health Affairs Synergy Fund award, the Georgia Research Alliance, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Childrens Healthcare of Atlanta, the Emory-UGA Center of Excellence for Influenza Research and Surveillance (Atlanta, GA USA), and a Woodruff Health Sciences Center 2020 COVID-19 CURE Award. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Cincinnati Children's Hospital Medical Center (Cincinnati, OH), and Emory University (Atlanta, Georgia) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data presented in the manuscript will be available upon reasonable request to the corresponding author.