Stay-At-Home Orders Are Associated With Emergence of Novel SARS-CoV-2 Variants

Background While public health strategies to contain the current coronavirus disease 2019 (COVID-19) pandemic are primarily focused on social distancing and isolation, emerging evidence suggest that in some regions social isolation failed to lead to further decrease in the number of COVID-19 deaths in the long run. This apparent paradox was particularly observed in the northern region of Brazil, in the state of Amazonas. We hypothesized that the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations, leading to more transmissible and pathogenic variants, could explain the lack of further reductions in COVID-19 new cases and related deaths in some regions. Our objective is to determine if social isolation is associated with the emergence of new SARS-CoV-2 variants, particularly the P.1 lineage and E484K mutants, in Brazil and in the state of Amazonas. Materials and methods We assessed the prevailing SARS-CoV-2 genomes present in Brazil available on the GISAID (Global Initiative on Sharing All Influenza Data) database collected between June 1, 2020, and January 31, 2021. Data regarding demographics, lineage, and prevalence of P.1 lineage and E484K mutations were obtained. Social isolation was measured using the Social Isolation Index (SII), which quantifies the percentage of individuals that stayed within a distance of 450 meters from their homes on a given day, between February 1, 2020, and January 24, 2021. The number of daily COVID-19 deaths was obtained from the Brazilian Ministry of Health (OpenDataSUS, 2021) between March 12, 2020, and January 10, 2021. SII was correlated with the prevalence P.1 lineage and E484K mutations in the eight following weeks. All univariate associations were estimated using the Spearman Correlation Index. 3D surfaces were employed to reflect the relationship between time, social isolation, and prevalence of genomic variants simultaneously. Results A total of 773 and 77 samples were obtained in Brazil and in the Amazonas state, respectively. In the state of Amazonas, SII on a given week was positively, significantly, and moderately or strongly (r > 0.6) correlated with the prevalence of both P.1 lineage and other E484K variants in the six following weeks after the SII on a given week. Conversely, in overall Brazil, correlations between SII and P.1 lineage and E484K variants were weaker and shorter, or negative, respectively. When SII was below 40%, P.1 lineage or E484K variants were not detected in the following weeks. When SII was above 40%, apparently exponential positive correlations between SII and prevalence of both P.1 lineage and E484K variants were observed. Conclusion The results of this study indicate that SII above 40% is associated with the emergence of SARS-CoV-2 E484K variants and P.1 lineage in the state of Amazonas, which was not observed in overall Brazil.