RESUMO
Viruses targeting mammalian cells can indirectly alter the gut microbiota, potentially compounding their phenotypic effects. Multiple studies have observed a disrupted gut microbiota in severe cases of SARS-CoV-2 infection that require hospitalization. Yet, despite demographic shifts in disease severity resulting in a large and continuing burden of non-hospitalized infections, we still know very little about the impact of mild SARS-CoV-2 infection on the gut microbiota in the outpatient setting. To address this knowledge gap, we longitudinally sampled 14 SARS-CoV-2 positive subjects who remained outpatient and 4 household controls. SARS-CoV-2 cases exhibited a significantly less stable gut microbiota relative to controls, as long as 154 days after their positive test. These results were confirmed and extended in the K18-hACE2 mouse model, which is susceptible to SARS-CoV-2 infection. All of the tested SARS-CoV-2 variants significantly disrupted the mouse gut microbiota, including USA-WA1/2020 (the original variant detected in the United States), Delta, and Omicron. Surprisingly, despite the fact that the Omicron variant caused the least severe symptoms in mice, it destabilized the gut microbiota and led to a significant depletion in Akkermansia muciniphila. Furthermore, exposure of wild-type C57BL/6J mice to SARS-CoV-2 disrupted the gut microbiota in the absence of severe lung pathology. IMPORTANCETaken together, our results demonstrate that even mild cases of SARS-CoV-2 can disrupt gut microbial ecology. Our findings in non-hospitalized individuals are consistent with studies of hospitalized patients, in that reproducible shifts in gut microbial taxonomic abundance in response to SARS-CoV-2 have been difficult to identify. Instead, we report a long-lasting instability in the gut microbiota. Surprisingly, our mouse experiments revealed an impact of the Omicron variant, despite producing the least severe symptoms in genetically susceptible mice, suggesting that despite the continued evolution of SARS-CoV-2 it has retained its ability to perturb the intestinal mucosa. These results will hopefully renew efforts to study the mechanisms through which Omicron and future SARS-CoV-2 variants alter gastrointestinal physiology, while also considering the potentially broad consequences of SARS-CoV-2-induced microbiota instability for host health and disease.
RESUMO
ImportanceAccess to testing is key to a successful response to the COVID-19 pandemic. ObjectiveTo determine the geographic accessibility to SARS-CoV-2 testing sites in the United States, as quantified by travel time. DesignCross-sectional analysis of SARS-CoV-2 testing sites as of April 7, 2020 in relation to travel time. SettingUnited States COVID-19 pandemic. ParticipantsThe United States, including the 48 contiguous states and the District of Columbia. ExposuresPopulation density, percent minority, percent uninsured, and median income by county from the 2018 American Community Survey demographic data. Main OutcomeSARS-CoV-2 testing sites identified in two national databases (Carbon Health and CodersAgainstCovid), geocoded by address. Median county 1 km2 gridded friction surface of travel times, as a measure of geographic accessibility to SARS-CoV-2 testing sites. Results6,236 unique SARS-CoV-2 testing sites in 3,108 United States counties were identified. Thirty percent of the U.S. population live in a county (N = 1,920) with a median travel time over 20 minutes. This was geographically heterogeneous; 86% of the Mountain division population versus 5% of the Middle Atlantic population lived in counties with median travel times over 20 min. Generalized Linear Models showed population density, percent minority, percent uninsured and median income were predictors of median travel time to testing sites. For example, higher percent uninsured was associated with longer travel time ({beta} = 0.41 min/percent, 95% confidence interval 0.3-0.53, p = 1.2x10-12), adjusting for population density. Conclusions and RelevanceGeographic accessibility to SARS-Cov-2 testing sites is reduced in counties with lower population density and higher percent of minority and uninsured, which are also risk factors for worse healthcare access and outcomes. Geographic barriers to SARS-Cov-2 testing may exacerbate health inequalities and bias county-specific transmission estimates. Geographic accessibility should be considered when planning the location of future testing sites and interpreting epidemiological data. Key PointsO_LISARS-CoV-2 testing sites are distributed unevenly in the US geography and population. C_LIO_LIMedian county-level travel time to SARS-CoV-2 testing sites is longer in less densely populated areas, and in areas with a higher percentage of minority or uninsured populations. C_LIO_LIImproved geographic accessibility to testing sites is imperative to manage the COVID-19 pandemic in the United States. C_LI