Abstract

BackgroundChildren are underrepresented in the COVID-19 pandemic and often experience milder disease than adolescents and adults. Reduced severity is possibly due to recent and more frequent seasonal human coronaviruses (HCoV) infections. We assessed the seroprevalence of SARS-CoV-2 and seasonal HCoV specific antibodies in a large cohort in north-eastern France.MethodsIn this cross-sectional seroprevalence study, serum samples were collected from children and adults requiring hospital admission for non-COVID-19 between February and August 2020. Antibody responses to SARS-CoV-2 and seasonal HCoV (229E, HKU1, NL63, OC43) were assessed using a bead-based multiplex assay, Luciferase-Linked ImmunoSorbent Assay, and a pseudotype neutralisation assay.FindingsIn 2,408 individuals, seroprevalence of SARS-CoV-2-specific antibodies was 7-8% with three different immunoassays. Antibody levels to seasonal HCoV increased substantially up to the age of 10. Antibody responses in SARS-CoV-2 seropositive individuals were lowest in adults 18-30 years. In SARS-CoV-2 seronegative individuals, we observed cross-reactivity between antibodies to the four HCoV and SARS-CoV-2 Spike. In contrast to other antibodies to SARS-CoV-2, specific antibodies to sub-unit 2 of Spike (S2) in seronegative samples were highest in children. Upon infection with SARS-CoV-2, antibody levels to Spike of betacoronavirus OC43 increased across the whole age spectrum. No SARS-CoV-2 seropositive individuals with low levels of antibodies to seasonal HCoV were observed.InterpretationOur findings underline significant cross-reactivity between antibodies to SARS-CoV-2 and seasonal HCoV, but provide no significant evidence for cross-protective immunity to SARS-CoV-2 infection due to a recent seasonal HCoV infection. In particular, across all age groups we did not observe SARS-CoV-2 infected individuals with low levels of antibodies to seasonal HCoV.FundingThis work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur, by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID), and by the REACTing (Research & Action Emerging Infectious Diseases), and by the RECOVER project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 101003589, and by a grant from LabEx IBEID (ANR-10-LABX-62-IBEID).

Highlights

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 100 million people since its discovery [1] and, as of February 2021, has led to almost 2.5 million deaths [2]

  • Our study provides a detailed characterization of humoral immunity to SEVERE ACUTE RESPIRATORY SYNDROME (SARS)-CoV-2 and seasonal coronaviruses in a study population comprising a wide age spectrum including one of the largest collection of samples from children assembled to date

  • We found that the immune response to SARS-CoV-2 is lower in adolescents and young adults compared to young children and older adults

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Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected at least 100 million people since its discovery [1] and, as of February 2021, has led to almost 2.5 million deaths [2]. SARS-CoV2 belongs to the Coronaviridae family in which 7 coronaviruses are known to exist associated with respiratory tract infections in humans [3]. Four of these are endemic to humans, including 2 alphacoronaviruses, 229E and NL63, and two betacoronaviruses OC43 and HKU1. Whereas the epidemiology of SARS-CoV and MERS-CoV is characterized by small and contained epidemics, seasonal human coronaviruses (HCoV) are endemic around the world [4]. After a small decrease in the seroprevalence to all four seasonal HCoV due to waning of maternal antibodies [5], seroprevalence rises rapidly in childhood, after which it remains stable in adults [6,7,8]. We assessed the seroprevalence of SARS-CoV-2 and seasonal HCoV specific antibodies in a large cohort in north-eastern France.

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