ABSTRACT
BACKGROUND: Immunological cross-reactivity between common cold coronaviruses (CCC) and SARS-CoV-2 might account for the reduced incidence of COVID-19 in children. Evidence to support speculation includes in vitro evidence for humoral and cellular cross-reactivity with SARS-CoV-2 in specimens obtained before the pandemic started. METHOD: We used retrospective health insurance enrollment records, claims, and laboratory results to assemble a cohort of 869,236 insured individuals who had a PCR test for SARS-CoV-2. We estimated the effects of having clinical encounters for various diagnostic categories in the year preceding the study period on the risk of a positive test result. FINDINGS: After adjusting for age, gender and care seeking behavior, we identified that individuals with diagnoses for common cold symptoms, including acute sinusitis, bronchitis, or pharyngitis in the preceding year had a lower risk of testing positive for SARS-CoV-2 (OR=0.76, 95%CI=0.75, 0.77). No reduction in the odds of a positive test for SARS-CoV-2 was seen in individuals under 18 years. The reduction in odds in adults remained stable for four years but was strongest in those with recent common cold symptoms. INTERPRETATION: While this study cannot attribute this association to cross-immunity resulting from a prior CCC infection, it is one potential explanation. Regardless of the cause, the reduction in the odds of being infected by SARS-CoV-2 among those with a recent diagnosis of common cold symptoms may have a role in shifting future COVD-19 infection patterns from endemic to episodic.