Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection
Irène A. Abela, Magdalena Schwarzmüller, Agnė Ulytė, Thomas Radtke, Sarah R. Haile, Priska Ammann, Alessia Raineri, Sonja Rueegg, Selina Epp, Christoph Berger, Jürg Böni, Amapola Manrique, Annette Audigé, Michael Huber, Peter W. Schreiber, Thomas Scheier, Jan Fehr, Jacqueline Weber, Peter Rusert, Huldrych F. Günthard, Roger D. Kouyos, Milo A. Puhan, Susi Kriemler, Alexandra Trkola, Chloé Pasin
Abstract
= 0.030). By investigating the systemic and mucosal immune responses to SARS-CoV-2 and HCoVs in a population without prior exposure to SARS-CoV-2 or vaccination, we identified specific antibody reactivities associated with lack of symptom development.IMPORTANCEKnowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020-2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.