Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China in late 2019 and rapidly spread across the globe, leading the World Health Organization (WHO) to declare a pandemic state on 11 March 2020 (1, 2). The virus has been widespread, causing waves of infections in almost all regions of the world (3). The first cases were confirmed in the state of São Paulo in February 2020. After that, actions were taken by the Ministry of Health in order to contain the emerging epidemic (4). As of today, 37.9 million cases in Brazil have resulted in 706,531 deaths, representing a mortality rate of 441.3 individuals per 100,000 inhabitants (accessed on 28 October 2023; available in https://covid.saude.gov.br//). This high mortality rate is related to the lack of a national policy against the disease, the increasing population mobility, especially in large urban centers, the return of face-to-face work activities, difficulties in implementing individual and community preventive measures to reduce the spread of COVID-19, and delays in vaccination have contributed to the emergence and spread of SARS-CoV-2 variants of concern (VOCs) across the country over time (5).

In Brazil, the pandemic was characterized by the co-circulation of multiple variants over time (6). The emergence of new variants was directly related to adaptive mutations in the viral genome that modified the pathogenic potential of SARS-CoV-2. A single amino acid change can dramatically affect a virus’s ability to evade the immune system and complicate the clinical status of infected individuals (7). Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and omicron (B.1.1.529) lineages were important variants associated with greater transmissibility or virulence, reduced neutralization by antibodies obtained through natural infection or vaccination, ability to avoid detection, and/or decreased therapeutic or vaccination efficacy (8).

Monitoring SARS-CoV-2 was possible due to recent technological and scientific advances in genome sequencing and bioinformatics tools, allowing almost real-time genomic surveillance and tracking the emergence and replacement dynamics of variant emergence and prevalence among populations (9). Several studies focusing on genomic surveillance have provided crucial information to understand the dynamics of SARS-CoV-2 lineages in the states or regions of Brazil due to the large differences between inter- and intra-state population sizes, concentration, and dynamics of human movement (10, 11). This proposal has been shown to be relevant to determine the spread of the virus based on the specific characteristics of the state in a refined resolution (11). In the Brazilian Northeast, 7.4 million cases of COVID-19 and 136,000 deaths have already been reported. Bahia, Ceará, and Pernambuco are the states with the highest incidence of cases and deaths in the region. In Sergipe state, 363,329 individuals were diagnosed with COVID-19, resulting in 6,539 deaths (accessed on 28 October 2023; available at https://covid.saude.gov.br//). At the moment, a single study has been identified in the literature related to genomic surveillance in Sergipe, and this analyzed genomes sequenced between March 2020 and February 2021 (5). This demonstrates the necessity to implement new research aimed at understanding the effects of the pandemic.

Therefore, this study aimed to assess the dynamics of SARS-CoV-2 variants from 2020 to 2022 in the state of Sergipe within Brazil. Knowledge gained would identify viral evolutionary patterns and behavior as it relates to epidemiological impacts.

This is a pioneering study of the state of Sergipe. The evolutionary history of circulating SARS-CoV-2 genomes over the last 3 years was reconstructed using phylogenetic analyses based on ML and the median-joining method. Our data support that B.1 was the first lineage detected in Sergipe (as recorded in Aracaju on 12 March 2020). However, Gurgel et al. (23) report in their study that the first case of COVID-19 in the state of Sergipe may have occurred a few months earlier, as samples from asymptomatic individuals sent for blood tests between the months of January and April 2020 by reasons unrelated to COVID-19 showed the presence of SARS-CoV-2 immunoglobulins (IgM and IgG) before the notification of clinical cases in the state. The country registered its first COVID-19 case in late February in São Paulo (4). In Bahia, the first confirmed SARS-CoV-2 infections occurred on 28 February, being the first case in the Northeast region⁵.

The lineages B.1, B.1.1, B.1.1.33, B.1.1.28, and B.1.212 were prevalent until mid-August 2020. In an analysis carried out by Dos Santos et al. (5), B.1 (58.5%), B.1.1.33 (17.1%), B.1.1.119 (12.2%), B.1.1.28 (9.8%), and B.1.212 (2.4%) were dominant from March to August 2020 in Sergipe. In late 2020, the variants zeta (P.2) (24) and gamma (P.1) (25), descendants of lineage variants B.1.1.28, emerged and were associated with the second phase of the pandemic. P.1 was identified in the state of Amazonas in mid-December 2020, with a proposed emergence around November (25, 26).

P.1 was dominant in infection cases by SARS-CoV-2, having their circulation on 17 January 2021. Some studies proposed that the emergence of three mutations E484K, N501Y, and K417T in the Spike protein allowed the virus to escape from the host immune response (27–29). In mid-January 2021, samples from 11 suspected cases and their contact reporting a travel history to/from Amazonas state were screened at the Central Laboratory of Health of the Bahia state (LACEN-BA). Genetic evidence has confirmed for the first time the circulation of the P.1 in the Brazilian Northeast (30). The study conducted by Dos Santos et al. (5) also confirms that P.1 circulated in Aracaju (Sergipe) on 17 January 2021 in a sample belonging to a resident from the city of Manaus (Amazonas) who traveled to Sergipe to visit his family (5).

Our results from the evolutionary analysis showed that B.1.1.28 is a common ancestor of P.1 and P.2. In the studies conducted by Varela et al. (31) and Harvey et al. (32), it was indicated that P.1 and P.2 descend from B.1.1.28 although they have different times of appearance and share the S: E484K mutation. A cluster formed by P.1, P.1.1, P.1.2, and P.1.7 demonstrates the ancestral relationship between these lineages, as reported by Varela et al. (31) and Machado et al. (11). In the present study, a shared ancestry between P.2 and P.7 was also observed similar to that suggested by Lamarca et al. (33).

Assessing the results, it was suggested that AY.99.2 (11.1%) became dominant in cases from September to December 2021. There are signs that the delta variant emerged in October 2020 on the Asian continent as has been classified by WHO (33). In Brazil, the first community-sustained transmission chains of the delta variant were registered in June 2021 in the state of Rio de Janeiro (34), and it has been widely detected in other Brazilian states over time (see footnote 5). Among the delta variants, the AY.99.2 was the most dominant, reaching 58% of all sublineages sampled during the period (35). Some evidence demonstrate that AY.99.2 emerged in Brazil; the first SARS-CoV-2 genomes from this lineage available in the GISAID database are from samples collected in April 2021 in the northeastern state of Ceará (36). Studies have identified mutations in the spike protein of the delta sublineages found in Brazil, and the most common mutations mentioned are T19R, T95I, E156G, DEL157/158, L452R, T478K, D614G, Q677H, P681R, D950N, V1104L, and L1265F⁷. Some of these mutations can be related to viral fitness advantages such as enhanced viral entry, pathogenesis, and immune escape (37, 38). Despite that, the number of hospitalizations declined from 6.9% (January to June 2021) to 3.6% (July to December 2021) during the community transmission of the delta variant with the progression of vaccination in the second half of 2021 in Sergipe (39).

The phylogenetic tree revealed that the samples of the delta variant formed a monophyletic clade. In an analysis using the neighbor-joining method with genomes from the delta lineage, a compatible structuring with a monophyletic clade was shown, and the omicron variant emerged from it (40).

In this study, the lineage BA.1.1 was reported as most frequent, followed by BA.1, BA.5.2, and BA.5.2.1. Genomic surveillance detected that in February 2022, the omicron variant was majority; 99.8% of the samples analyzed around the country being positive for the variant (see footnote 5). From January to September, BA.1 (4,253 genomes) and BA.1.1 (2,521 genomes) were also prevalent in infection cases by SARS-CoV-2 in the northeast Brazil (see footnote 5). Since the beginning of the pandemic, the SARS-CoV-2 genome has been rapidly evolving. This is mostly due to the inherent polymerase mistakes and host immune selection factors (32). The omicron variant is the most mutated variant containing more than 60 mutations in its genome. In total, 32 of these mutations lie within the receptor binding domain (RBD) of the spike protein (41, 42). The large number of mutations associated with the spike RBD domain can be related to infectivity rates, high transmission capacity, and rapid dispersal potential (26). Among the mutations identified in the omicron variants, 14 are exclusive and found in all the omicron variants (43).

Our phylogenetic tree for omicron VOC suggests the existence of two main clades, one composed of the sublineages linked to BA.1 and the other associated with BA.2, BA.4, and BA.5 variants. In a study developed by Veneziano et al. (44) with Omicron SARS-CoV-2 genomes in Italy, a group composed of BA.1 and another by BA.2, BA.4, and BA.5 lineages was identified. Six mutations have been identified in all the omicron variants, excluding omicron BA.1: Del24-26, V213G, T376A, S371F, D405N, and R408S (43). These mutations may have contributed to the structure of the clades of the phylogenetic tree and also in the haplotype network, as observed in other organisms (45, 46). Notably, our study presents a limitation due to the fact that in some months of 2020 and 2022, there were no records of SARS-CoV-2 genomes in the GISAID database. However, there is agreement between our genomic surveillance results and those observed in other states of Brazil.

Finally, the increase in the average number of SARS-CoV-2 lineages during the studied periods is related to the average number of infections in both unvaccinated and vaccinated individuals. Tarkowski et al. (47) demonstrated that vaccinated individuals presented higher levels of IgG against viral proteins of spike protein-1 (S1) and receptor-binding domain (RBD), which resulted in a better immune response to B.1 and P.1 variants although immune activation is less noticeable in response to the B.1.617.2 variant. A similar study revealed differences in the efficiency of humoral activity in vaccinated individuals against B.1.617.1, B.1.617.2, B.1.351, and P.1 lineages due to mutations in the spike protein (S) (48). Unvaccinated individuals are intrinsically associated with daily cases and deaths. Martins-Filho et al. (39) studied the dynamics of hospitalizations and the predominance of delta and omicron variants in the Northeast of Brazil and found that during the circulation of the delta variant (July to December 2021), the majority of deaths occurred in people who were not vaccinated or who had not completed the vaccination schedule. Furthermore, in 2020, vaccines were scarce, with high hospitalization rates (46% of the population with active infection) (39).

Our data suggest a correlation between the increase in the mean number of variant lineage strains and the mean number of infections in unvaccinated and vaccinated individuals. It is important to note that 3 years after the beginning of the SARS-CoV-2 pandemic, and despite the availability of several vaccines for 2 years, the restrictive measures to contain SARS-CoV-2 spreading were met with several challenges among most countries. In particular, the recent variants are generating new outbreaks of infection, even in countries where the level of vaccinations is high. However, it becomes necessary for continuous monitoring of the most predominant SARS-CoV-2 lineages as well as their specific dynamic and processes of evolution. Therefore, this knowledge gain and continual analysis of variant lineages is imperative for epidemiologists to define public health measures, perform adequate diagnostic tests, and strategically employ vaccines (49).

Despite the number of positive cases of COVID-19 in Sergipe, these did not have minimum values to be submitted for genetic sequencing; and we were unable to establish a stratified correlation between the number of lineages and the severity of COVID-19 cases in both vaccinated and unvaccinated individuals. This correlation could have demonstrated how lineage variability impacts the severity of infections.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

Ethical approval was not required for the study involving humans in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and the institutional requirements.

MF and VQ: conceptualization. MF, KF, LS, FN, and JR: investigation. MF, KF, and ER: methodology. MF and KF: formal analysis. MF: project administration. MF and TM: writing – original draft. MF, TM, ML, MA, SS, KF, JR, LS, and CS: writing – review and editing. All authors contributed to the article and approved the submitted version.