Prior infection with intestinal coronaviruses moderates symptom severity and mortality in patients with COVID-19: A hypothesis and preliminary evidence

The pandemic of acute respiratory illness caused by the novel betacoronavirus SARS-CoV-2, officially designated COVID-19, has attained the proportions of a global health crisis. Though all nations of the world have been affected by this disease, there have been marked cross-national variations in prevalence, severity and mortality rates. Various explanations, based on demographic, social and climatic factors, have been suggested to account for this variability, but these remain unverified to date. Based on recent research findings suggesting that human enterocytes may serve as a point of entry for SARS-CoV-2, leading to intestinal viral replication, this paper puts forward the hypothesis that prior intestinal infection with coronaviruses, either symptomatic or asymptomatic, may moderate this process and minimize the severity of SARS-CoV-2 infection. This hypothesis is supported by evidence on the gastrointestinal manifestations of SARS-CoV-2 and related infections, on the geographical patterns observed in the variability of COVID-19 mortality, and on the occurrence and geographical distribution of outbreaks of diarrheal disease, as well as asymptomatic infection, with human coronaviruses as verified by direct or serological testing. Preliminary supporting evidence based on national and international health statistics is presented, along with suggestions on more robust methods by which this hypothesis may be tested. If the proposal put forth in this paper can be confirmed either wholly or in part, it would have significant implications in terms of strategies aimed at minimizing the severity of COVID-19 in a clinical setting.