Our study investigated the prevalence of the SARS-CoV-2 recombinant lineage XBB in the RS state, South Brazil, from November 2022 to April 2023. During this period, the RS state government recorded 265,371 new confirmed cases of SARS-CoV-2 infection and 834 deaths (Fig. 1). We observed an increase in SARS-CoV-2-positive cases and deaths following the introduction of XBB into the state on EW 48/2022. Subsequently, from EW 6/2023 onwards, when the first cases of infection by XBB.1.5 were identified, we observed another increase in these parameters, although with less intensity.
A total of 357 SARS-CoV-2-positive samples were sequenced for this study. However, 17 sequences were excluded due to not meeting the quality criteria (i.e., had less than 75% genome coverage breadth, and/or more than 3000 N, and/or possessed a bad score). Additionally, we incorporated 389 publicly available sequences from the GISAID database (Table S1). A total of 729 SARS-CoV-2 genomes were analyzed to determine the predominant variant during the study period. Among these genomes, 586 sequences were identified as the Omicron variant, while the remaining 143 were classified as recombinant variant XBB. Complete epidemiological data were available for 99.04% (722) of individuals infected with SARS-CoV-2 (Table 1 and S1).
Table 1
Epidemiological data of SARS-CoV-2-positive patients
| Omicron positive (n = 586) | XBB positive (n = 143) |
Age (median) | 52 | 57 |
< 18 (number) | 16 | 6 |
18–60 | 318 | 74 |
> 60 | 248 | 60 |
Female (%) | 350 (59.7) | 76 (53.15) |
The first case of XBB.1 infection was detected on November 27, 2022 (EW 48/2022) (Fig. 2 and Table S1). Subsequently, we identified a few cases of XBB.1 infection. However, starting from EW 9/2023, the number of cases experienced a substantial increase, ultimately establishing XBB as the dominant lineage, accounting for 83.3% of all cases in EW 10/2023 (Fig. 2A and C). Among 729 SARS-CoV-2 sequences (Fig. 2B), we identified a total of forty-five Pangolin lineages. The most frequently detected lineage was BQ.1.1 (257 sequences, 35.4%), followed by BE.9 (117 sequences, 16.12%), XBB.1.5 (97 sequences, 13.36%), BQ.1.22 (59 sequences, 8.13%), XBB.1 (32 sequences, 4.41%), BQ.1 (25 sequences, 3.44% each), and BQ.1.1.18 (19 sequences, 2.62%) (Fig. 1B and C). The remaining thirty-eight lineages had frequencies of less than 2%, collectively representing 16.94% of the total sequences.
Clinical data was available for 62.2% (89 subjects) of the 143 patients infected with the XBB variant (Fig. 3A). Among these patients, a significant majority of 97.7% (87 individuals) successfully recovered from the SARS-CoV-2 infection, while a small fraction, 2.3% (two individuals), died due to COVID-19 complications. Only one of the recovered patients required hospitalization (ICU), due to causes other than COVID-19, whereas hospitalization was required for those who died (Table S2). Among the recovered group, 41.6% and 33.7% were aged between 40 and 59 years or > 60 years, respectively. The remaining 24.7% represented individuals up to 11 years old (3 individuals) and those aged 12–39 years (17 individuals). Both individuals who died were over 80 years old, with one having received only two vaccine doses. Notably, five individuals were unvaccinated against SARS-CoV-2, predominantly those in the 0–11 age group, who were not yet eligible for vaccination according to the Ministry of Health guidelines. This group also included one individual aged 12–39 and one over 60, both of whom were eligible but unvaccinated. Most subjects, 41.6% (37 individuals), received three vaccine doses, followed by 27% (24 individuals) who received four doses, and 16.9% (15 individuals) who received two doses. Indeed, only six individuals were up-to-date with their vaccination schedule. The first three doses administered were monovalent vaccines against SARS-CoV-2. From february, 2023 was introduced the bivalent vaccine. Given that the bivalent vaccine is effective against severe cases and death caused by the XBB variant infection, and conversely, the monovalent vaccine has considerably reduced efficacy, it is hypothesized that considering vaccination alone, only 6.7% of the individuals were fully protected against the XBB infection.
According to the health data repositories of the Brazilian Ministry of Health, 59.5% of the individuals (50 individuals) were reinfected with the XBB variant (Fig. 3B). A total of 28.6% (24 individuals) experienced their first infection with the XBB infection. For 11.9% (10 individuals), there is an absence of recorded data on both previous infections and the XBB infection itself, suggesting a potential failure in the reporting system. 43.1% of the reinfected individuals were over 60 years of age, followed by those in the 40–59 age group (41.2%), and 15.7% aged between 12 and 39 years. Conversely, 50% of those experiencing their first infection were aged between 40–59 years. There was considerable variability in the interval between infection and the administration of the last vaccine dose. However, it is noteworthy that 58.3% of the infected individuals had received their last dose or booster more than a year prior. Among the reinfected individuals, all had previously received at least one vaccine dose, indicating the presence of hybrid immunity against the virus.
We analyzed the interval between the occurrence of XBB infection and the administration of the last vaccine dose (Fig. 4). The results revealed that among individuals aged 12–39, 40–60, and > 60 years, the median intervals were 403, 442, and 351 days, respectively. The three infected individuals in the 0–11 age group had not received any vaccine doses.
The mutation profile of XBB in the RS state is presented in Fig. 5. The XBB recombinant lineage exhibited a total of 90 mutations, including 78 single nucleotide polymorphisms (SNPs), comprising 52 transitions and 26 transversions, 5 substitutions, and 7 deletions (Fig. 5A and B; Table S3). Of these mutations, (1) was located in the 5'-UTR, (31) in the ORF1ab, (40) in the S gene, (3) in ORF3a, (2) in the E gene, (3) in the M gene, (2) in ORF6, (1) in ORF7b, (1) in ORF8, (4) in the N gene, (1) in the intergenic UTR, and (1) in the 3'-UTR (Fig. 4 and Table S3). Among the observed SNPs, 77.2% (61) were non-synonymous mutations, particularly those occurring in the S gene. This accumulation of mutations in the XBB variant's S gene, particularly within the Receptor Binding Domain (RBD), endows it with the ability to evade antibodies acquired through vaccination and previous infections (Fig. 5B).
BA.2.10.1 and BA.2.75 represent the parental lineages of XBB. To assess the distinctive mutations among these lineages, we employed a Venn diagram (Fig. 6). XBB displayed 12 unique mutations that are absent in its parent lineages. Among these mutations, ten were identified in the S gene, comprising nine non-synonymous mutations and one deletion (V83A, del144/144, H146Q, Q183E, V213E, R346T, L368I, V445P, F486P, F490S). Additionally, there was one mutation in the ORF1ab (K47R) and one in the ORF8 (G8*). XBB circulation in RS did not exhibit the characteristic mutations associated with these lineages, namely G959P (ORF1b), E180V (S gene), K478R (S gene), F486S (S gene), R493Q (S gene), Q613H (S gene), and S84L (ORF8) (Table S4).