Abstract:

This review article is comprised of three parts: Part 1 (this part) introduces the subject and investigates how cross-reactive coronaviruses provide preexisting immunity to SARS-CoV-2. Part 2 will explore preexisting immunity from other microorganisms, while Part 3 will examine preexisting immunity from non-COVID vaccinations and discuss the overall article. Despite authoritative statements that SARS-CoV-2 was a novel virus, to which no one had immunity, several early studies suggested that preexisting immunity to SARS-CoV-2 was a very real phenomenon. SARS-CoV-2, in fact, shares a strong genetic identity with other human coronaviruses (between 65% and 82%), so it is no surprise to find abundant evidence of cross-reactivity between SARS-CoV-2 and the common cold coronaviruses. Fewer studies have investigated whether cross-reactivity to these coronaviruses induces preexisting immunity. Where preexisting immunity has been tested, there was an association between protection against COVID-19 and the cross-reactive memory T and B cells of the adaptive immune system and the trained immunity of the innate immune system. Cross-reactive antibodies present a conundrum, as in some instances, they are protective, but in other cases, they worsen COVID-19. The factors that determine whether an antibody is protective or pathogenic are mainly unknown. It is important to investigate this for both the use of plasma therapy and vaccine development. Similarly, the trained immunity response may occasionally worsen inflammation. The proportion of samples showing preexisting immunity may, in fact, be understated, as generally only peripheral blood immune cells, rather than samples of bone marrow or respiratory tract mucosa, were tested; mucosal secretory IgA antibodies are consistently protective.

Keywords: COVID-19, SARS-CoV-2, coronaviruses, preexisting immunity, cross-reactivity