Global Prevalence and Clinical Features of Low Pathogenic Human Coronaviruses with Potential Impact on COVID-19: Systematic Review, Meta-Analysis and Bioinformatic Mapping

BACKGROUND: An emerging theory suggests that pre-exposure to low pathogenic human coronaviruses (LPH-CoV) may cross-protect SARS-CoV-2 infection, the causative agent of COVID-19. To understand the potential impact of LPH-CoV on the COVID-19 pandemic, we comprehensively characterized the global prevalence and clinical features of LPH-CoV infection, as well as the genetic relationship with SARS-CoV-2. METHODS: Articles were systematically searched to identify studies related to LPH-CoV, including 229E, NL63, OC43 and HKU1. We calculated the pooled prevalence and clinical features using a random-effects model. Viral genome sequences were retrieved for phylogenetic and similarity analyses. FINDINGS: From returned 3225 records, 157 studies comprising 1161300 individuals with respiratory symptoms were finally included for our analyses. Based on LPH-CoV viral RNA positivity, we estimated a pooled global prevalence of 5·24% (95% CI 4·68-5·83%, I 2 =97%). The highest detection rate was found in Oceania (14·40%), followed by Africa (6·64%), Europe (5·51%), North America (5·42%), South America (4·86%) and Asia (4·62%). Among the four genotypes, OC43 is most prevalent (2·40%, 95% CI 2·15-2·66%, I 2 =95%), followed by NL63 (1·60%), HKU1 (1·04%) and 229E (0·97%). Fever, cough, headache, sore throat and rhinorrhea are most common symptoms. Unexpectedly, over 25% patients developed pneumonia. Bioinformatic analysis revealed a noticeable genetic affinity, and importantly the viral proteins that are responsible for immune response share about 20-50% sequence similarity between LPH-CoV and SARS-CoV-2. INTERPRETATION: LPH-CoV are circulating among the global population, and they share genetic similarities with SARS-CoV-2. The wide prevalence of LPH-CoV may have a fundamental impact on the global COVID-19 pandemic.