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

Abstract

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. In this study, we investigated the emergence and spread of SARS-CoV-2 genetic variants in Missouri, examined viral shedding over time, and analyzed the associations among emerging genetic variants, viral shedding, and disease severity. The study population included COVID-19 positive patients from CoxHealth (Springfield, Missouri) and University of Missouri Health Care (UMHC; Columbia, Missouri) between March and October 2020. All positive SARS-CoV-2 nasopharyngeal swabs (n=8,735) from March-October 2020 were collected. Available viral genomes (n=184) from March to July were sequenced. Hospitalization status and length of stay were extracted from medical charts of 1,335 patients (UMHC and sequenced patients). The primary outcome was hospitalization status (yes or no) and length of hospital stay (days). For the 1,335 individuals, 44 were hospitalized and four died due to COVID-19. The average age was 34.35 (SD=16.82), with 55.1% females (n=735) and 44.7% males (n=596). 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 most Missouri viruses harbored Spike-D614G mutations, many 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 through October. Accounting for comorbidities, individuals test-positive for COVID-19 with high viral loads were less likely to be hospitalized (odds ratio=0.39, 95% confidence interval=0.20, 0.77) and more likely to be discharged from the hospital sooner (hazard ratio=2.9, p=0.03) 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.