Vigilância genômica de variantes de SARS-CoV-2 no estado de Minas Gerais – Brasil

Abstract

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. COVID-19 was first identified in December 2019 in the city of Wuhan, China, in a group of patients with previously unknown pneumonia. In Brazil, the first suspected case of COVID-19 was reported on January 27, 2020 and the first case confirmed by members of our research group was on February 26, 2020, in São Paulo, of a patient who had returned from Italy. The clinical manifestations of COVID-19 are diverse, ranging from mild to severe symptoms. The severity of symptoms can range from classic febrile respiratory symptoms to severe viral pneumonia with life-threatening respiratory failure. As soon as the COVID-19 pandemic showed high numbers of infections around the world, vaccine initiatives that could eradicate the pandemic began to be developed and tested. SARS-CoV-2 has a positive-stranded RNA genome approximately 30,000 bases in length. Its genomic structure is shared with other β-coronaviruses and has six functional open reading frames (ORFs) that are arranged in order from 5' to 3', respectively: replicase (ORF1a/ORF1b), spike (S), envelope (E), membrane (M) and nucleocapsid (N). The spike protein (S) is responsible for the interaction of the viral envelope with the cell receptor ACE2 and the process of virus entry. Mutations in this region can alter the transmissibility of the virus, as well as the neutralization by antibodies generated by vaccination programs. Viral genomic surveillance can be used by public health agencies to control and prevent transmission, in addition to identifying critical regions for strengthening hospital structures and vaccination. In this dissertation, we propose to evaluate the distribution of SARS-CoV-2 strains through a viral genomic surveillance program and its consequences in the epidemiological scenario of COVID-19 in the state of Minas Gerais. In Chapter I, we present the development and standardization of a rapid and effective methodology for identifying SARS-CoV-2 variants, by genotyping the defining viral mutations of the main lineages by real-time PCR. This methodology was effective and sensitive in the identification of SARS-CoV-2 variants confirmed by the sequencing of the complete viral genome, which allowed us to establish the Genomic Surveillance Observatory - OviGen coordinated by our research group in partnership with the Health Department of MG (SES-MG), Belo Horizonte City Hall (PBH) and Ezequiel Dias Foundation (FUNED). In Chapter II, we present the results of OviGen through a retrospective population-based study for a genomic surveillance of SARS-CoV-2 variants in the 28 Regional Health Units of MG, from March to April 2021, the period of greatest registration number of cases and deaths and an increase in the prevalence of variants such as Alpha, Gamma and Zeta. It was also possible to identify other variants, with a lower frequency of circulation, which were classified as “other” strains by genotyping and confirmed as variants B.1.35, B1.1.28, P.4, P.5 and P.7 by complete genome sequencing. Using phylogeny and phylogeographic strategies, we demonstrate the introduction of VOC Gamma in the state of MG on January 7, 2021 and its dispersion in the state of MG from the southeast region, bordering Rio de Janeiro, reaching about 100% of cases of COVID-19 infection on 27 weeks (July 2021). Our results demonstrated the increase in mean viral load among patients infected with the gamma variant, demonstrating the impact of the introduction of this VOC and the consequent increase in transmission rates and severity of COVID-19 cases, reinforcing the importance of viral genomic surveillance studies in the control and transmission of the pandemic.