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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.
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Introduction A major barrier for successful therapeutic approaches for COVID-19 is the inability to diagnose COVID-19 during the viral replication stage, when drugs with potential antiviral activity could demonstrate efficacy and preclude progression to more severe stages. Reasons that hamper an earlier diagnosis of COVID-19 include the unspecific and mild symptoms during the first stage, the delay in the diagnosis and specific management caused by the requirement of a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 for the diagnosis of COVID-19, and the insufficient sensitivity of the RT-PCR-SARS-CoV-2, converse to what is recommended for a screening test during an outbreak. More sensitive and earlier diagnostic tools for COVID-19 should be unraveled as a key strategy for a breakthrough change in the disease course and response to specific therapies, particularly those that target the blockage of viral shedding. We aimed to create an accurate, sensitive, easy-to-perform, and intuitive clinical scoring for the diagnosis of COVID-19 without the need for an RT-PCR-SARS-CoV-2 (termed The AndroCoV Clinical Scoring for COVID-19 Diagnosis), resulting from a 1,757 population cohort, to eventually encourage the management of patients with a high pre-clinical likelihood of presenting COVID-19, independent of an RT-PCR-SARS-COV-2 test, to avoid delays and loss of appropriate timing for potential therapies. Methods This is a post-hoc analysis of clinical data prospectively collected of the Pre-AndroCoV and AndroCov Trials, which resulted in scorings for the clinical diagnosis of COVID-19 based on the likelihood of presenting with actual COVID-19 according to the number of symptoms, presence of anosmia, and known positive household contact. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and accuracy were calculated for subjects screened in two different periods and both periods together, for females, males, and both, in a total of nine different scenarios, according to combinations of one, two, or three or more symptoms or the presence of anosmia in subjects without known positive household contacts, and no symptoms, one, two, or three or more symptoms, or presence of anosmia or ageusia in subjects with known positive household contacts. Scorings that yielded the highest pre-test probability, sensitivity, and accuracy were selected. Results Of the 1,757 patients screened, 1,284 were diagnosed with COVID-19. The scoring that required: (1) two or more symptoms, or anosmia or ageusia alone, for subjects without known contact; or (2) one or more symptoms, including anosmia or ageusia alone, when with known positive contacts presented the highest accuracy (80.4%) among all combinations attempted, and higher sensitivity (85.7%) than RT-PCR-SARS-CoV-2 commercially available kit tests. Conclusion The AndroCoV clinical scoring for COVID-19 diagnosis was demonstrated to be a feasible, easy, costless, and sensitive diagnostic tool for the clinical diagnosis of COVID-19. Because the clinical diagnosis of COVID-19 avoids delays in specific treatments, particularly for high-risk populations, prevents false-negative diagnosis, and reduces diagnostic costs, this diagnostic tool should be considered as an option for COVID-19 diagnosis, at least while SARS-CoV-2 is the prevailing circulating virus and vaccination rate is below the required for herd immunity.