Dynamics of transmission of COVID-19 in Brazil
The first confirmed SARS-CoV-2 infection in Brazil was on 26 February 2020 in the state of São Paulo (SP), in a traveler returning from Italy (Fig. 1a). On March 17, 2020, the first death related to COVID-19, a 61-year-old man, was reported in the same state4,5. Four days later, all Brazilian states reported at least one confirmed case of COVID-19, and the Brazilian Ministry of Health (BRMoH) declared an outbreak of large-scale community transmission of the virus6. By April 10, 2020, the virus had already reached remote locations, such as the Yanomami indigenous community located in the state of Roraima, northern Brazil6 (Fig. 1a).
Fig. 1: Key events after the first confirmed SARS-CoV-2 infection in Brazil.
aTimeline of key events of SARS-CoV-2 in Brazil. bEpidemic curve showing the progression of the number of daily viral infections reported in Brazil since the start of the epidemic (grey) and deaths (red) in the same period, with the phases of restriction indicated by the horizontal bar in the lower part cMap of cumulative cases of SARS-CoV-2 per 100,000 inhabitants in Brazil until June 2021.
After the World Health Organization (WHO) declared the SARS-CoV-2 outbreak a public health emergency of international concern on January 30, 2020, the Brazilian government introduced restrictive measures to mitigate the spread viral (Fig. 1a)7. The main measure involved social isolation, followed by the closure of schools, universities and non-essential shops8. Additional measures include the mandatory use of personal protective masks9, the cancellation of events that were expected to attract large numbers of people and tourists and the opening of only services considered essential such as markets and pharmacies8,10 . However, as the epidemic grew, the restrictive measures were gradually eased to mitigate the negative impacts on the economy. In particular, even during periods of restriction, travel between Brazilian states remained largely possible, allowing the transmission of SARS-CoV-2 throughout the country11. Travel was likely linked to the emergence of more contagious viral lineages, such as VOC Gamma (lineage P.1) and VUM Zeta (lineage P.2). In particular, these variants may have contributed to a second wave that was more severe in terms of infections and deaths than the first wave (Fig. 1b)11,12,13,14.
The number of deaths from COVID-19 in Brazil rose steadily after March 2021. It reached a daily total of 4,250 deaths in April 2021, the highest number of daily fatalities from COVID-19 in the entire world (Figure 1b). Signs of health system collapse were reported in numerous cities across the country. The situation worsened after the emergence of multiple VOCs and VUMs during a slow vaccination campaign15. Vaccination in Brazil began on January 17, 2021, when the Butantan Institute imported the first 6 million doses of CoronaVac (a whole-virus inactivated vaccine) from Sinovac Biotech (Fig. 1a)16,17. As of February 16, 2022, approximately 71.8% of the Brazilian population had been vaccinated with the first dose of any of the available vaccines (CoronaVac, AstraZeneca, Pfizer, and Janssen), but only 22% were fully vaccinated ( with a single dose of Janssen). or two doses of any other vaccine)18.
When analyzing the total number of reported cases of COVID-19 up to the end of September 2021, we observed that the Brazilian region with the highest population density (southeast) also contained the highest number of reported cases in the country, with the state of São. Paulo documents the largest number of cases (n= 4,369,410) in this period (Fig. 1c). However, when we considered the incidence rate (number of reported cases per population) by state, we found that the Midwest, Brazil’s least populated region, had the highest incidence rate, with 13,604.23 cases per 100,000 inhabitants1.
Genomic data of SARS-CoV-2
As part of this study, a total of 3,866 near-complete genome sequences were obtained from SARS-CoV-2 RT-qPCR positive samples. SARS-CoV-2 sequencing spanned from February 2020 to June 2021, with samples from 8 of the 27 Brazilian states (São Paulo, 3,309; Rio Grande do Sul, 48; Paraná, 55; Minas Gerais, 80 ; Mato Grosso do Sul, 36). ; Mato Grosso, 51; Bahia, 224) and a neighboring country, Paraguay (n= 63). Almost half of the sequences were from southeastern Brazil, which included the states of São Paulo and Rio de Janeiro that reported the most cases (Fig. 1c)6. The sequenced genomes were from samples collected from 2,023 women and 1,843 men (Supplementary Tables 1 and 2), with a mean age of 41.72 years (range: 1–90 years). All samples tested contained sufficient viral genetic material (≥2 ng µl-1) for library preparation. For positive samples, PCR cycle threshold (Ct) values averaged 19.93 (range: 10.75–30). Sequences had an average genome coverage of 95% (range: 80–99.99), and average genome coverage was usually higher for samples with lower Ct values (Supplementary Figure 1). Epidemiological information and sequencing statistics for the sequences generated from Brazil and Paraguay are presented in Supplementary Tables 1 and 2, respectively. Sequences were assigned to 39 different PANGO lineages based on the dynamic nomenclature proposed for SARS-CoV-2 lineages (Supplementary Figure 1 and Tables 1 and 2) and submitted to GISAID following WHO guidelines (Supplementary Tables 1 and 2). 2) (Pangolin version 3.1.7, August 2021).
Phylogenetic inference and lineage diversity
The rapid spread of SARS-CoV-2, together with the reported circulation of several VOCs and VUMs in Brazil, prompted an intensification of genomic surveillance by the National SARS-CoV-2 Pandemic Alert Network in late December 2020. As of June 30, 2021, more than 17,135 SARS-CoV-2 genomes from the 27 Brazilian states had been deposited in the GISAID database (Fig. 2a). The states with the largest number of sequenced genomes were São Paulo (n= 9,600) and Rio de Janeiro (n= 2.031). Although genomic surveillance began as soon as the first confirmed infections were detected in Brazil, at the end of June 2021 there was still little genomic data from some states, such as Roraima (n= 29), acres (n= 29), Rondonia (n= 37), Tocantins (n= 27), Piauí (n= 19) and the Federal District (n= 33) (Fig. 2a). Half of all Brazilian genomes were deposited in early 2021, suggesting that surveillance was at its peak in the second wave following the emergence of Gamma (and other VOCs (e.g. Alpha/B. 1.1.7)) and VUM (eg Zeta) throughout the country (Fig. 2b).
Fig. 2: Phylogenetic and dynamic analysis of the SARS-CoV-2 lineage in Brazil.
a, Map of Brazil with the number of sequences in GISAID as of June 30, 2021. The map is colored by geographic macroregion: North (red), Northeast (green), Southeast (purple), Midwest ( light blue) and South (light orange). AC, Acre; AL, Alagoas; AP, Amapá; AM, Amazons; BA, Bahia; EC, Ceara; DF, Federal District; ES, Espírito Santo; GO, Goiás; MA, Maranhao; MT, Mato Grosso; MS, Mato Grosso do Sul; MG, Minas Gerais; PA, Pará; PB, Paraíba; PR, Paraná; PE, Pernambuco; PI, Piauí; RR, Roraima; RO, Rondônia; RJ, Rio de Janeiro; RN, Rio Grande do Norte; RS, Rio Grande do Sul; SC, Santa Catarina; SP, Sao Paulo; SE Sergipe; TO, Tocantins. bTemporal sampling of sequences in Brazilian states through time with VOCs highlighted and annotated according to their PANGO lineage assignment. cTime-resolved maximum-likelihood phylogeny containing high-quality near-complete genome sequences from Brazil (n= 3,866) obtained from this study, analyzed against a backdrop of global reference sequences (n= 25,288). VUMs and COVs are highlighted in the phylogeny. dSources of viral introductions in Brazil characterized as external introductions from the rest of the world. eSources of viral exchanges (imports and exports) inside and outside Brazil. fNumber of viral exchanges in Brazilian regions counting state changes from the root to the tips of the phylogeny in c.
To understand the dynamics of the spread of SARS-CoV-2 in Brazil, we combined epidemiological data with phylodynamic analyzes for a dataset consisting of 25,288 globally representative genomes, including the genomes sequenced in this study.n= 3,866) sampled from December 26, 2019 to June 28, 2021 (Figs. 2c and 3). A date-stamped phylogeny of these data indicated that most Brazilian sequences were interspersed with those introduced from several countries (Figs. 2c,d). This pattern further indicated that the co-circulation of multiple SARS-CoV-2 lineages over time was linked to multiple imports followed by large local transmissions concomitant with a high number of infections (Fig. 2c,d) .
Fig. 3: Fully annotated Brazilian SARS-CoV-2 temporal tree.
Time-resolved maximum-likelihood phylogeny containing 17,135 high-quality Brazilian SARS-CoV-2 near-complete genome sequences (n= 3,866 generated in this study) analyzed against a backdrop of global reference sequences. VUMs and VOCs are highlighted.
Using an ancestral location state reconstruction on the dated phylogeny, we were able to infer the number of viral imports and exports between Brazil and the rest of the world, and between individual Brazilian regions (hereafter called north, northeast, midwest, southeast, and southern regions) (Fig. 2d–f). Most of the imported introductions (estimated to be 114 independent) were largely from Europe (Figure 2d), occurring before the application of restriction measures (April 2020) when the epidemic was progressing rapidly (Figure 2d,e). However, at least 33 introduction events were inferred to have occurred during the implementation of the preventive measures until August 2020 (Fig. 2d,e) and thus before these measures were relaxed . Finally, although Brazil was a major virus importer, there were approximately 10 times more inferred export events outside of Brazil than viral introductions…