Phylodynamic analysis of SARS-CoV-2 spread in Rio de Janeiro, Brazil, highlights how metropolitan areas act as dispersal hubs for new variants. (preprint)

During the first semester of 2021, all of Brazil has suffered an intense wave of COVID-19 associated with the Gamma variant. In July, the first cases of Delta variant were detected in the state of Rio de Janeiro. In this work, we have employed phylodynamic methods to analyze more than 1,600 genomic sequences of Delta variant collected until September in Rio de Janeiro to reconstruct how this variant has surpassed Gamma and dispersed throughout the state. After the introduction of Delta, it has initially spread mostly in the homonymous city of Rio de Janeiro, the most populous of the state. In a second stage, dispersal occurred to mid- and long-range cities, which acted as new close-range hubs for spread. We observed that the substitution of Gamma by Delta was possibly caused by its higher viral load, a proxy for transmissibility. This variant turnover prompted a new surge in cases, but with lower lethality than was observed during the peak caused by Gamma. We reason that high vaccination rates in the state of Rio de Janeiro were possibly what prevented a higher number of deaths. Impact statementUnderstanding how SARS-CoV-2 spreads is vital to propose efficient containment strategies, especially when under the perspective of new variants emerging in the next year. Still, models of SARS-CoV-2 dispersal are still largely based in large cities from high-income countries, resulting in an incomplete view of the possible scenarios consequent of a new variant introduction. The work improves this discussion by reconstructing the spatio-temporal dispersal of Delta variant since its introduction in Rio de Janeiro, a densely populated region in South America. We also analyzed the epidemiological outcome of this spread, with a decrease in lethality rate uncommon to the observed in other countries. Data summaryFour supplementary figures, one supplementary table and one supplementary file are available with the online version of this article. Raw short reads of the newly sequenced genomes are available at SRA-NCBI database (https://www.ncbi.nlm.nih.gov/sra) under the BioProject PRJNA774631 and the assembled genomes are deposited at GISAID database (https://www.gisaid.org/) under the accession numbers listed in Table S1. Other genomic sequences used in the analyses are listed in Table S2. Epidemiological data for the state of Rio de Janeiro was obtained from https://www.saude.rj.gov.br/informacao-sus/dados-sus/2020/11/covid-19.

Emergence of within-host SARS-CoV-2 recombinant genome after coinfection by Gamma and Delta variants (preprint)

Since the first reports of patients coinfected by two genetically-distinct lineages of SARS-CoV-2, the scientific community raised concerns about the recombination of intra-host viral RNA sequences as a possible mechanism underlying the emergence of novel variants. Indeed, this phenomenon occurs at a relatively high frequency among betacoronaviruses. Nevertheless, the few existing studies about recombination between genetically-distinct lineages of SARS-CoV-2 are restricted to detect the inter-host dissemination of genomes post-recombination events. However, the high genomic similarity between the current co-circulating lineages challenges the identification of these events. Here, we report the first case of intra-host SARS-CoV-2 recombination during a coinfection by the variants of concern (VOC) AY.33 (Delta) and P.1 (Gamma) supported by sequencing reads harboring a mosaic of lineage-defining mutations. By using next-generation sequencing reads intersecting regions that simultaneously overlap lineage-defining mutations from Gamma and Delta, we were able to identify a total of six recombinant regions across the SARS-CoV-2 genome within a sample. Four of them mapped in the spike gene and two in the nucleocapsid gene. We detected mosaic reads harboring a combination of lineage-defining mutations from each VOC. To our knowledge, this is the first report of intra-host RNA-RNA recombination between two lineages of SARS-CoV-2, which can represent a threat to public health management during the COVID-19 pandemic due to the possibility of the emergence of viruses with recombinant phenotypes.

Turnover of SARS-CoV-2 lineages shaped the pandemic and enabled the emergence of new variants in the state of Rio de Janeiro, Brazil (preprint)

In the present study, we provide a retrospective genomic epidemiology analysis of the SARS-CoV-2 pandemic in the state of Rio de Janeiro, Brazil. We gathered publicly available data from GISAD and sequenced more 1,927 new genomes sampled periodically from March 2021 to June 2021 from 91 out of the 92 cities of the state. Our results showed that the pandemic was characterized by three different phases driven by a successive replacement of lineages. All stages occurred in distinct mortality and mobility contexts, with higher evidence of social distancing measures being observed in early pandemic and relaxed in the last two phases. Interestingly, we noticed that viral supercarriers accounted for the overwhelming majority of the circulating virus (> 90%) among symptomatic individuals in the state. Moreover, SARS-CoV-2 genomic surveillance also revealed the emergence and spread of two new variants (P.5 and P.1.2) firstly reported in this study. Altogether, our findings provided important lessons learned from the different epidemiological aspects of the SARS-CoV-2 dynamic in the state of Rio de Janeiro that have a strong potential to shape future decisions aiming to improve public health management and understanding mechanisms underlying virus dispersion.

Identification of SARS-CoV-2 P.1-related lineages in Brazil provides new insights about the mechanisms of emergence of Variants of Concern (preprint)

One of the most remarkable features of the SARS-CoV-2 Variants of Concern (VOC) is the unusually large number of mutations they carry. However, the specific factors that drove the emergence of such variants since the second half of 2020 are not fully resolved. In this study, we described a new SARS-CoV-2 lineage provisionally designated as P.1-like-II that, as well as the previously described lineage P.1-like-I, shares several lineage-defining mutations with the VOC P.1 circulating in Brazil. Reconstructions of P.1 ancestor sequences demonstrate that the entire constellation of mutations that define the VOC P.1 did not accumulate within a single long-term infected individual, but was acquired by sequential addition during interhost transmissions. Our evolutionary analyses further estimate that P.1-ancestors strains carrying half of the P.1-lineage-defining mutations, including those at the receptor-binding domain of the Spike protein, circulated cryptically in the Amazonas state since August 2020. This evolutionary pattern is consistent with the hypothesis that partial human population immunity acquired from natural SARS-CoV-2 infections during the first half of 2020 might have been the major driving force behind natural selection that allowed VOCs' emergence and worldwide spread. These findings also support a long lag-time between the emergence of variants with key mutations of concern and expansion of the VOC P.1 in Brazil.