Endemic coronavirus infections are associated with strong homotypic immunity in a US cohort of children from birth to 4 years.

Abstract

The endemic coronaviruses OC43, HKU1, NL63 and 229E cause cold-like symptoms and are related to SARS-CoV-2, but their natural histories are poorly understood. In a cohort of children followed from birth to 4 years, we documented all coronavirus infections, including SARS-CoV-2, to understand protection against subsequent infections with the same virus (homotypic immunity) or a different coronavirus (heterotypic immunity). Mother-child pairs were enrolled in metropolitan Cincinnati during the third trimester of pregnancy in 2017-18. Mothers reported their child's socio-demographics, risk factors, and weekly symptoms. Mid-turbinate nasal swabs were collected weekly. Blood was collected at 6 weeks, 6, 12, 18, 24 months and annually thereafter. Infections were detected by testing nasal swabs by an RT-PCR multi-pathogen panel and by serum IgG responses. Health care visits were documented from pediatric records. Analysis was limited to 116 children with high sample adherence. Re-consent for monitoring SARS-CoV-2 infections from June 2020 through November 2021 was obtained for 74 (64%) children. We detected 345 endemic coronavirus infections (1.1 infections/child-year) and 21 SARS-CoV-2 infections (0.3 infections/child-year). Endemic coronavirus and SARS-CoV-2 infections were asymptomatic or mild. Significant protective homotypic immunity occurred after a single infection with OC43 (77%) and HKU1 (84%), and after two infections with NL63 (73%). No heterotypic protection against endemic coronaviruses or SARS-CoV-2 was identified. Natural coronavirus infections were common and resulted in strong homotypic immunity but not heterotypic immunity against other coronaviruses, including SARS-CoV-2. Endemic coronavirus and SARS-CoV-2 infections in this US cohort were typically asymptomatic or mild.