Multifactorial SARS-CoV-2 seroprofiling dissects interdependencies with human coronaviruses and predicts neutralization activity

Abela, I. A.; Pasin, C.; Schwarzmueller, M.; Epp, S.; Sickmann, M.; Schanz, M. M.; Rusert, P.; Weber, J.; Schmutz, S.; Audige, A.; Maliqi, L.; Hunziker, A.; Hesselman, M. C.; Niklaus, C. R.; Gottschalk, J.; Schindler, E.; Wepf, A.; Karrer, U.; Wolfensberger, A.; Rampini, S. K.; Meyer Sauteur, P. M.; Berger, C.; Huber, M.; Boeni, J.; Braun, D. L.; Marconato, M.; Manz, M. G.; Frey, B. M.; Guenthard, H. F.; Kouyos, R. D.; Trkola, A.

Definition of SARS-CoV-2 antibody responses is essential to verify protective immunity following infection and vaccination. Here, we devised a versatile serological test, named ABCORA, that is based on a multifactorial analysis of SARS-CoV-2 and circulating human coronavirus (HCoV) antibody responses. Utilizing empirical tailored cut-offs and computational approaches based on training and validation cohorts comprising pre-pandemic (N=825) and SARS-CoV-2 infected plasma donors (N=389), we defined several analysis strategies that allow a highly accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity. Intriguingly, HCoV reactivity was significantly higher in SARS-CoV-2 negative donors. Amongst SARS-CoV-2 infected individuals, elevated SARS-CoV-2 responses were linked to higher HCoV activity suggesting that pre-existing HCoV immunity may confer protection against SARS-CoV-2 acquisition and promote development of SARS-CoV-2 specific antibody responses. Deciphering interdependencies between SARS-CoV-2 and HCoV immunity should be enforced as understanding their impact on infection may allow soliciting cross-protective activities for broader coronavirus prevention.