Monitoring the Establishment of VOC Gamma in Minas Gerais, Brazil: A Retrospective Epidemiological and Genomic Surveillance Study

Abstract

Since its first identification in Brazil, the variant of concern (VOC) Gamma has been associated with increased infection and transmission rates, hospitalizations, and deaths. Minas Gerais (MG), the second-largest populated Brazilian state with more than 20 million inhabitants, observed a peak of cases and deaths in March-April 2021. We conducted a surveillance study in 1240 COVID-19-positive samples from 305 municipalities distributed across MG's 28 Regional Health Units (RHU) between 1 March to 27 April 2021. The most common variant was the VOC Gamma (71.2%), followed by the variant of interest (VOI) zeta (12.4%) and VOC alpha (9.6%). Although the predominance of Gamma was found in most of the RHUs, clusters of Zeta and Alpha variants were observed. One Alpha-clustered RHU has a history of high human mobility from countries with Alpha predominance. Other less frequent lineages, such as P.4, P.5, and P.7, were also identified. With our genomic characterization approach, we estimated the introduction of Gamma on 7 January 2021, at RHU Belo Horizonte. Differences in mortality between the Zeta, Gamma and Alpha variants were not observed. We reinforce the importance of vaccination programs to prevent severe cases and deaths during transmission peaks.

Keywords: PCR-genotyping; SARS-CoV-2 spread; genome sequencing; phylodinamics; variants.

Figure 1

Workflow strategy for genomic evaluation of SARS-CoV-2 variants in MG. Twenty samples/week positive for SARS-CoV-2 with Ct < 30 were obtained from 28 Regional Health Units. Samples were screened for specific mutations in the Spike gene through PCR-genotyping (K417T, E484K and N501Y). Samples with mutations in each position are marked with green check symbol. Samples that presented different mutational profile are marked with red interrogation symbol. The description of the 1240 samples obtained, collection date, municipality of origin and genotyping result are included in Supplementary Table S1. A subset (239 samples) was selected for genome sequencing and phylogenetic analysis. A total of 78 new Gamma genomes were generated by our study and the genomes were used to infer the probable date of insertion in MG.

Figure 2

Epidemiological and viral data during Gamma introduction in MG state (45/2020–13/2021). (A) Numbers of positive and death cases in Brazil. (B) The first and second vaccine doses distributed in MG. (C) Distribution of median Cts values for SARS-CoV-2 N gene and MS2 (intern control gene) from 119,507 positive samples from 343 municipalities from MG.

Figure 3

Spatio-temporal distribution of cases (A) and deaths (B) during Gamma introduction in MG.

Figure 4

Distribution frequencies, symptoms and comorbidities of SARS-CoV-2 lineages in MG. Spatial frequency distribution of samples genotyped as VOC Gamma (A), Zeta lineage (B), VOC Alpha (C), and “Other” lineages (D). Comorbidities (E) and symptoms (F) reported by patients related to the SARS-CoV-2 variants identified.

Figure 5

Maximum likelihood phylogeny inference corroborating the lineage classification using a global reference dataset (see material and methods section). Blue circles represent genomes generated in our study (n = 239). Grey lines represent reference genomes.

Figure 6

Timing and geographical introduction of novel Gamma genomes in MG state (molecular clock). (A) Time-scaled phylogeographic estimated with TreeTime under a fixed evolutionary rate (10⁻³) and a six-states symmetric discrete model (North, Northeast, Southeast, South, Centra-West and MG. (B) Number of SARS-CoV-2 introduction events for the MG state compared to other Brazilian regions, according to the timescale analysis.