Humoral immunity to SARS-CoV-2 and seasonal coronaviruses in children and adults in north-eastern France

Tom Woudenberg (1, 2) , Stéphane Pelleau (1, 2) , Francois Anna (3) , Mikael Attia (4) , Francoise Donnadieu (1, 2) , Alain Gravet (5) , Caroline Lohmann (5) , Helene Seraphin (6) , Raphael Guiheneuf (6) , Catherine Delamare (7) , Karl Stefic (8) , Julien Marlet (8) , Etienne Brochot (9, 10) , Sandrine Castelain (9, 10) , Olivier Augereau (11) , Jean Sibilia (12) , Francois Dubos (13) , Damia Meddour (13) , Christele Gras-Le Guen (14) , Marianne Coste-Burel (14) , Berthe-Marie Imbert-Marcille (14) , Anne Chauvire-Drouard (15) , Cyril Schweitzer (16) , Amelie Gatin (17) , Sandra Lomazzi (18) , Aline Joulie (19) , Herve Haas (19) , Aymeric Cantais (20) , Frederique Bertholon (20) , Marie-France Chinazzo-Vigouroux (8) , Mohamed S. Abdallah (21) , Laurence Arowas (22) , Pierre Charneau (3) , Bruno Hoen (23) , Caroline Demeret (4) , Sylvie van Der Werf (4, 24) , Arnaud Fontanet (25, 26) , Michael White (1, 2)

1 Epidémiologie et Analyse des Maladies Infectieuses - Infectious Disease Epidemiology and Analytics
2 Malaria : parasites et hôtes - Malaria : parasites and hosts
3 Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology
4 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
5 Centre Hospitalier de Mulhouse, site du Hasenrain (Mulhouse)
6 Centre Hospitalier Simone Veil de Beauvais [Beauvais]
7 CHR Metz-Thionville - Centre hospitalier régional Metz-Thionville
8 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
9 AGIR - Agents infectieux, résistance et chimiothérapie - UR UPJV 4294
10 Laboratoire de Virologie [CHU Amiens]
11 Hôpitaux Civils de Colmar
12 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
13 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
14 CHU Nantes - Centre Hospitalier Universitaire de Nantes
15 CIC Nantes - Centre d’Investigation Clinique de Nantes
16 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
17 Service de Pédiatrie [CHRU Nancy]
18 CRB Nancy - Centre de Ressources Biologiques - [Nancy]
19 CHU-Lenval - Hôpitaux Pédiatriques de Nice Lenval
20 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
21 ARS - agence régionale de santé Hauts-de-France
22 ICAReB - Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources
23 Direction de la recherche médicale de l'Institut Pasteur
24 CNR - laboratoire coordonnateur - Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris]
25 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
26 CNAM - Conservatoire National des Arts et Métiers [CNAM]

Background: Children 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. Methods: In 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. Findings: In 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 (52) 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. Interpretation: Our 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.

Mots clés: COVID-19; SARS-CoV-2; antibody response; seasonal coronaviruses; sero-epidemiology; seroprevalence

Domaines: Sciences du Vivant [q-bio]; Virologie; Santé publique et épidémiologie

Tom Woudenberg, Stéphane Pelleau, Francois Anna, Mikael Attia, Francoise Donnadieu, et al.. Humoral immunity to SARS-CoV-2 and seasonal coronaviruses in children and adults in north-eastern France. EBioMedicine, 2021, 70, pp.103495. ⟨10.1016/j.ebiom.2021.103495⟩. ⟨hal-03591559⟩