Every winter, seasonal coronaviruses are responsible for repeated colds and bronchitis from early childhood onwards. The question of whether the four seasonal coronaviruses can confer cross-protective immunity for COVID-19 was recently raised when it was demonstrated that some individuals had antibodies and immunity cells recognizing the SARS-CoV-2 virus before it was in active circulation. The existence of such immunity would have a major impact on our understanding of how the outbreak is likely to develop. Children with COVID-19 generally have mildly symptomatic forms that often go unnoticed, but in some rare cases they may develop severe symptoms that resemble Kawasaki disease. In a recent study, scientists from the Institut Pasteur, Inserm, the Paris Public Hospital Network (AP-HP) and Université de Paris demonstrated that frequent infection with seasonal coronaviruses in children offers no protection against infection with the SARS-CoV-2 virus that causes COVID-19 or the severe forms resembling Kawasaki disease. The results were pre-published on medRxiv on June 30, 2020.
A consortium of Institut Pasteur laboratories and clinicians from the AP-HP, Inserm and Université de Paris carried out a study from March 1 to June 1, 2020 in seven hospitals in and around Paris involving 775 children (aged 0 to 18), 36 of whom presented with a syndrome resembling Kawasaki disease. The aim of the PED-COVID study, coordinated by Necker Hospital and the Institut Pasteur, was to determine the frequency, type and concentration of antibodies produced by children in response to infection and their capacity to neutralize the SARS-CoV-2 virus. Antibody frequency and titers against the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured for a subset of patients who had tested seropositive for SARS-CoV-2 with no (or few) symptoms, and for patients admitted to hospital for Kawasaki-like disease, in comparison with seronegative patients.
The average prevalence rate of the SARS-CoV-2 virus in patients with no (or few) symptoms was 11.7% of the population under study. More than half (69.4%) of these children had never had characteristic symptoms of infection. Neutralizing antibodies were found in 56% of the seropositive children, with a relative frequency increasing over time (reaching 100% at the end of the study, two months after the peak of the outbreak). More than two-thirds of children with a syndrome resembling Kawasaki disease tested seropositive for the SARS-CoV-2 virus.
The presence and rate of antibodies against the four seasonal coronaviruses, found in 67-100% of children depending on the virus, were comparable in seronegative children and children who were seropositive for the COVID-19 causative virus, with either Kawasaki-like disease or no (or few) symptoms.
The results show that children often have asymptomatic or mildly symptomatic forms of COVID-19 and develop antibodies that are usually neutralizing. "Infection with seasonal coronaviruses does not offer significant protection against infection with the SARS-CoV-2 virus and related conditions such as the Kawasaki-like disease," comments Marc Eloit,* last author of the study and Head of the Pathogen Discovery laboratory at the Institut Pasteur. This study confirms the very high frequency and significant level of antibodies against seasonal coronaviruses in the general population – although prior infections do not prevent new infections with these viruses every winter. "If the COVID-19 causative virus behaves like seasonal coronaviruses, this observation calls into question whether the population will be able to reach a sufficient level of immunity to prevent the regular reemergence of the disease," concludes Marc Eloit.
* Marc Eloit is also a Professor at the Alfort National Veterinary School.
SARS-CoV-2 infection, antibody production and their neutralizing activity are not prevented by Seasonal Coronaviruses infection in children, MedRxiv, 30 juin 2020
Isabelle Sermet-Gaudelus1,2,3*, Sarah Temmam4*, Christèle Huon4, Sylvie Behillil5,6, Vincent Gajdos7,8, Thomas Bigot4,9, Thibaut Lurier10,11,12, Delphine Chrétien4, Marija Backovic13, Agnès Moisan-Delaunay14, Flora Donati5,6, Mélanie Albert5,6, Elsa Foucaud15, Bettina Mesplées16, Grégoire Benoist17, Albert Faye18, Marc Duval-Arnould19, Célia Cretolle2, Marina Charbit2, Mélodie Aubart2, Johanne Auriau2, Mathie Lorrot20, Dulanjalee Kariyawasam2, Laura Fertitta2, Gilles Orliaguet2, Bénédicte Pigneur2, Brigitte Bader-Meunier2, Coralie Briand16, Vincent Enouf5,6,21, Julie Toubiana2,3,22, Tiffany Guilleminot23, Sylvie van der Werf5,6, Marianne Leruez-Ville23, Marc Eloit4,24
1 Institut Necker Enfants Malades, INSERM U 1171. Paris 75015, Paris France
2 Hôpital Necker-Enfants Malades. Assistance Publique Hôpitaux de Paris. Paris 75015. France
3 Université de Paris. Paris 75015, France
4 Pathogen Discovery Laboratory, Department of Virology, Institut Pasteur, Paris, France
5 Molecular Genetics of RNA Viruses, Department of Virology, CNRS UMR3569, University of Paris, Institut Pasteur, Paris, France
6 National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France
7 Hôpital Antoine Beclere. 92140 Clamart, France
8 Centre for Research in Epidemiology and Population Health, INSERM UMR1018, Villejuif, France
9 Hub de Bioinformatique et Biostatistique – Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS, Paris, France
10 Université Clermont Auvergne, INRAE, VetAgro Sup, UMR EPIA, F-63122 Saint-Genès-Champanelle, France
11 Université de Lyon, INRAE, VetAgro Sup, UMR EPIA, F-69280 Marcy l’Etoile, France
12 Université de Lyon, INRAE, VetAgro Sup, Usc 1233 UR RS2GP, F-69280 Marcy l’Etoile, France
13 Structural Virology Unit, Institut Pasteur, Paris 75015, France
14 Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France
15 Hôpital Jean Verdier, 93140 Bondy, France
16 Hôpital Louis Mourier, 92700 Colombes. France
17 Hôpital Ambroise Paré, Boulogne Billancourt 92100. France
18 Hôpital Robert Debré, Paris 75019. France
19 Hôpital Kremlin Bicêtre, 94270 Le Kremlin-Bicêtre. France
20 Hôpital Armand Trousseau, 75012 Paris. France
21 Plateforme de microbiologie mutualisée (P2M), Pasteur International Bioresources Network (PIBnet), Institut Pasteur, Paris, France
22 Unité Biodiversité et Epidemiologie des Bacteries Pathogènes, Institut Pasteur, Paris, France
23 Laboratoire de Microbiologie, Hôpital Necker-Enfants Malades ; Paris 75015, France
24 Ecole Nationale Vétérinaire d’Alfort, 94704 Maisons Alfort, France