Abstract
While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are asymptomatic while others succumb to virus infection within days. Presently, the factors responsible for disease severity are not fully understood. One factor that may influence virus control is pre-existing immunity conferred by an individual’s past exposures to common cold human coronaviruses (HCoVs). Here, we describe previous literature and a new, murine study designed to examine cross-reactive immune responses between SARS-CoV-2 and common cold HCoVs (represented by prototypes OC43, HKU1, 229E, and NL63). Experimental results have been mixed. In SARS-CoV-2-unexposed humans, cross-reactive serum antibodies were identified toward nucleocapsid (N) and the spike subunit S2. S2-specific antibodies were in some cases associated with neutralization. SARS-CoV-2-unexposed humans rarely exhibited antibody responses to the SARS-CoV-2 spike subunit S1, and when naïve mice were immunized with adjuvanted S1 from either SARS-CoV-2 or common cold HCoVs, S1-specific antibodies were poorly cross-reactive. When humans were naturally infected with SARS-CoV-2, cross-reactive antibodies that recognized common cold HCoV antigens increased in magnitude. Cross-reactive T cells, like antibodies, were present in humans prior to SARS-CoV-2 exposures and increased following SARS-CoV-2 infections. Some studies suggested that human infections with common cold HCoVs afforded protection against disease caused by subsequent exposures to SARS-CoV-2. Small animal models are now available for the testing of controlled SARS-CoV-2 infections. Additionally, in the United Kingdom, a program of SARS-CoV-2 human challenge experiments has received regulatory approval. Future, controlled experimental challenge studies may better define how pre-existing, cross-reactive immune responses influence SARS-CoV-2 infection outcomes.
Highlights
Given that many individuals have been exposed to common cold human coronaviruses (HCoVs) and have generated HCoV-specific B cell and T cell responses [46,47], a pertinent question is whether common cold HCoV-specific antibodies and T cells cross-react with SARS-CoV-2
Mice primed with S1 proteins of OC43, NL63, 229E, and HKU1 all exhibited a poor response toward SARS-CoV-2 S1 (Figure 1A)
T cells may exhibit a variety of effector functions toward SARS-CoV-2 or common cold HCoVs including the secretion of cytokines/chemokines, the killing of SARS-CoV-2 infected cells
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that was first identified in Wuhan China in December 2019 [1,2]. It has since been the cause of an unprecedented global pandemic. The first isolation of OC43 was reported to have been by McIntosh et al at the National Institutes of Health, USA These investigators used specimens from patients with common cold symptoms and employed an embryonic trachea organ culture method that was previously developed by Tyrell and colleagues to isolate virus [26,32,33,34,35]. ACE2 binding [6,22,25,32,34,36,38,39,41,42,43,44,45]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
