Investigation of pre-existing immunity to coronaviruses: implications for immunopathology and pathophysiology of COVID-19 disease

It is unknown how prior exposure to commonly circulating human coronaviruses (HCoV) impacts immunity against highly-pathogenic species (SARS, SARS-CoV-2 and MERS). There is limited data across Europe, Asia and Africa on the prevalence of infection and seroconversion against widely circulating and mildly symptomatic HCoVs (229E, NL63, OC43 and HKU1). 

There is a current supposition that antibody-dependent-enhancement (ADE) may play a role in the pathophysiology of COVID-19. ADE occurs when non-neutralising antiviral proteins facilitate virus entry into host cells, leading to increased infectivity in the cells. In such cases, higher viremia has been measured and the clinical course of disease can be more severe. In preclinical animal models, immunopathology was observed after challenge following vaccination with some SARS vaccines. Therefore, concerns have been raised about the impact of immunopathology and ADE on prophylactic vaccination against SARS and possibly SARS-CoV-2. 

Our goal is to perform detailed systems serology of pre-existing immunity in children and adults, from the UK and Africa, towards novel and commonly circulating coronaviruses. 

These studies highlight the limited knowledge in the field, and the need for a systematic approach to investigating cross-reactive humoral immunity against HCoV to inform the immunopathology and pathophysiology of COVID-19.