Increased SAR-CoV-2 shedding associated with reduced disease severity despite continually emerging genetic variants

Since the first report of SARS-CoV-2 in December 2019, genetic variants have continued to emerge, complicating strategies for mitigating the disease burden of COVID-19. Positive SARS-CoV-2 nasopharyngeal swabs (n=8,735) were collected from Missouri, USA, from March-October 2020, and viral genomes (n=178) were sequenced. Hospitalization status and length of stay were extracted from medical charts of 1,335 patients and integrated with emerging genetic variants and viral shedding analyses for assessment of clinical impacts. Multiple introductions of SARS-CoV-2 into Missouri, primarily from Australia, Europe, and domestic states, were observed. Four local lineages rapidly emerged and spread across urban and rural regions in Missouri. While the majority of Missouri viruses harbored Spike-D614G mutations, a large number of unreported mutations were identified among Missouri viruses, including seven in the RNA-dependent RNA polymerase complex and Spike protein that were positively selected. A 15.6-fold increase in viral RNA levels in swab samples occurred from March to May and remained elevated. Accounting for other comorbidities, individuals test-positive for COVID-19 with high viral loads were less likely to be hospitalized (odds ratio=0.39, 95% confidence interval [CI]=0.20, 0.77) and had shorter hospital stays (hazard ratio=0.34, p=0.003) than those with low viral loads. Overall, the first eight months of the pandemic in Missouri saw multiple locally acquired mutants emerge and dominate in urban and rural locations. Although we were unable to find associations between specific variants and greater disease severity, Missouri COVID-positive individuals that presented with increased viral shedding had less severe disease by several measures.