Evidence for increased SARS-CoV-2 susceptibility and COVID-19 severity related to pre-existing immunity to seasonal coronaviruses

The importance of pre-existing immune responses to seasonal endemic coronaviruses (HCoVs) for the susceptibility to SARS-CoV-2 infection and the course of COVID-19 is the subject of an ongoing scientific debate. Recent studies postulate that immune responses to previous HCoV infections can either have a slightly protective or no effect on SARS-CoV-2 pathogenesis and, consequently, be neglected for COVID-19 risk stratification. Challenging this notion, we provide evidence that pre-existing, anti-nucleocapsid antibodies against endemic α-coronaviruses and S2 domain-specific anti-spike antibodies against β-coronavirus HCoV-OC43 are elevated in patients with COVID-19 compared to pre-pandemic donors. This finding is particularly pronounced in males and in critically ill patients. Longitudinal evaluation reveals that antibody cross-reactivity or polyclonal stimulation by SARS-CoV-2 infection are unlikely to be confounders. Thus, specific pre-existing immunity to seasonal coronaviruses may increase susceptibility to SARS-CoV-2 and predispose individuals to an adverse COVID-19 outcome, guiding risk management and supporting the development of universal coronavirus vaccines.

• Wratil, P. R.
• Schmacke, N. A.
• Karakoc, B.
• Dulovic, A.
• Junker, D.
• Becker, M.
• Rothbauer, U.
• Osterman, A.
• Spaeth, P. M.
• Ruhle, A.
• Gapp, M.
• Schneider, S.
• Muenchhoff, M.
• Hellmuth, J. C.
• Scherer, C.
• Mayerle, J.
• Reincke, M.
• Behr, J.
• Kääb, S.
• Zwissler, B.
• von Bergwelt-Baildon, M.
• Eberle, J.
• Kaderali, L.
• Schneiderhan-Marra, N.
• Hornung, V.
• Keppler, O. T.