Longitudinal Analysis of Humoral and Cellular Immunity in SARS-CoV-2 Exposed Families

Abstract

Identification of previous SARS-CoV-2 infection typically relies on serology, yet T cells play a key role in the adaptive immune response against SARS-CoV-2. Here, we investigated in parallel the SARS-CoV-2 specific humoral and cellular responses as well as endemic human coronavirus specific humoral and cross-reactive cellular responses in a family cohort comprising 164 children and 235 adults at 3-4 and 11-12 months after contact with SARS-CoV-2 . While the majority of adults had a combined serological and T cell response, relatively more children showed a T cell response only than a combined response. The magnitude of the T cell response was significantly correlated with symptoms and the humoral response. Moreover, SARS-CoV-2 infection significantly boosted endemic coronavirus specific cellular response. Overall our data suggest discordant humoral and cellular responses, reflecting either sensitization or mild infection with rapid viral clearance. Consequently, limiting epidemiologic analysis to SARS-CoV-2 antibodies may underestimate infection rates in children.

Note:
Clinical Trial Registration Details: This study was registered at the German Clinical Trials Register (DRKS), study ID 00021521, conducted according to the Declaration of Helsinki, and designed, analyzed and reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.

Funding Information: This work was financially supported by the State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism (grant numbers FKZ 3-4332.62-NMI-67 and FKZ 3-4332.62-NMI-68 to NS-M), the EU Horizon 2020 research and innovation program (grant agreement number 101003480 – CORESMA to NS-M) and the Ministry of Science, Research and the Arts Baden-Württemberg within the framework of the special funding line for COVID-19 research to the Freiburg, Tübingen, Ulm and Heidelberg centers. The work of JSW was supported by the Bundesministerium für Bildung und Forschung (BMBF, FKZ:01KI20130, FKZ:16LW0005 and FKZ:01DP21014).

Declaration of Interests: AD has given sponsored talks for Luminex and Sino Biological in the past. NSM was a speaker at Luminex user meetings in the past. The NMI is involved in applied research projects as a fee for services with Luminex. JSW is an inventor on patent applications on the SARS-CoV-2 T cell epitopes described in this manuscript secured under the numbers 20_169_047.6 and 20_190_070.1. The other authors declare no competing interests.

Ethics Approval Statement: The multi-center study was initiated by the four University Children’s Hospitals of Freiburg, Heidelberg, Tübingen and Ulm in Baden-Württemberg, Germany, and approved by the independent ethics committee of each center. This part of the study was conducted by the University Children’s Hospital, Tübingen, Germany. Ethics approval was obtained from the independent ethics committee of the Medical Faculty, University of Tübingen (293/2020BO2). Written informed consent was obtained from adult participants and from parents or legal guardians on behalf of their children at both sampling time points.

Keywords: T cell response, SARS-CoV-2, antibodies, children, adults, family, household exposure