Is Cross-Reactive Immunity Triggering COVID-19 Immunopathogenesis?

Abstract

The serological responses to both SARS-CoV-1 and SARS-CoV-2 virus have some unique characteristics that suggest cross-reactive priming by other human coronaviruses (hCoVs). The early kinetics and magnitude of these responses are, in some cases, associated with worse clinical outcomes in SARS and COVID-19. Cross-reactive hCoV antibody responses have been detected in both SARS and COVID-19 patients. There is also evidence that pre-existing T cell immunity to common cold coronaviruses can prime the response to SARS-CoV-2. Studies in non-human primates show that SARS-CoV-1 S-protein vaccine-induced antibodies are associated with acute lung injury in macaques challenged with SARS-CoV-1. Here we discuss the potential of cross-reactive immunity to drive the immunopathogenesis of COVID-19 and its implications for current efforts to develop immune-based therapies and vaccines.

Keywords: COVID-19; SARS-CoV-2; antibody-dependent enhancement; cross-reactivity; human coronaviruses; immunopathogenesis.

Figure 1

Illustrates the potential effects of an antibody response to infection by a common human coronavirus (Ab hCoVs, red line point 1) generated prior to SARS-CoV-2 infection and the induction of SARS-CoV-2 antibodies (blue line point 2) that cross-react with hCoVs. According to this hypothesis, in the absence of a previous hCoV infection, the antibody response to SARS-CoV-2 would follow a slower kinetics with a peak following that of viral replication, thus inducing a mild to moderate disease (lower panel). In contrast, a pre-existing antibody response to hCoVs would be followed by a very rapid (anamnestic) increase in SARS-CoV-2 antibodies that would precede the peak of viral replication (upper panel), thus inducing conditions for antibody-dependent enhancement or immunopathology by other antibody-dependent mechanisms leading to severe disease.