![]() ![]() Further complicating the control of the virus is the lack of genomic surveillance among rural populations. Consequently, while emerging SARS-CoV-2 variants are often detected in high-resource settings with genome sequencing capabilities, their origins remain poorly defined. ![]() ![]() Ease of travel has allowed new variants to quickly spread from essentially any location to a global scale 11. The rapid evolution of the severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease 2019 (COVID-19), has resulted in the emergence of multiple variants with increased virus transmissibility 1, 2, 3, immune evasion 4, 5, 6, 7, 8, and pathogenicity 9, 10. This study demonstrates that rural communities may be a crucial source of SARS-CoV-2 evolution and transmission, highlighting the need to expand surveillance and resources to rural populations for COVID-19 mitigation. Positive selection was detected at N:204 among rural samples but was not evident in urban samples, suggesting that viruses may encounter distinct selection pressures in rural versus urban communities. Further analyses revealed that the nucleocapsid protein (N):R203K/G204R paired substitutions, which were detected disproportionately across multiple Pango lineages, were more associated with urban than rural sequences. Phylodynamic analyses showed that frequent bi-directional diffusions occurred between rural and urban communities in Southwest Missouri, and that four out of seven Missouri rural-origin lineages spread globally. Genomic analyses revealed 53 SARS-CoV-2 Pango lineages in our study samples, with 14 of these lineages identified only in rural samples. We collected 544 urban and 435 rural COVID-19-positive respiratory specimens from an overall vaccine-naïve population in Southwest Missouri between July and December 2020. In this study, we aim to investigate the role of rural communities in the evolution and transmission of SARS-CoV-2 during the early pandemic. Consequently, how rurally circulating SARS-CoV-2 viruses contribute toward emerging variants remains poorly understood. Despite this, surveillance efforts are biased toward urban centers. In the United States, rural populations comprise 60 million individuals and suffered from high COVID-19 disease burdens. ![]()
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