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Background and Objectives: Since its appearance in 2019, multiple risk factors have been identified for presenting a severe form of COVID-19 and different vaccines have also been developed to prevent severe manifestations. However, despite a vaccination history, some cases progress to complications or even death. The objective of this study was to determine the strength of the association between the severity of COVID-19 and the history of vaccination in patients treated at a public reference hospital in Mexico City. Methods: This was a non-experimental, retrospective, and analytical epidemiological study of cases and controls. The study population was people treated at a concentration hospital for COVID-19 care between July 1, 2021, and June 30, 2022, in Mexico City. Results: 132 participants (44 cases and 88 controls) were included in the study. The risk factors most strongly associated with COVID-19 severity were age greater than or equal to 60 years, presenting 22 breaths per minute at the first medical evaluation, systolic blood pressure greater than or equal to 140 millimeters of mercury, and a history of at least one chronic comorbidity. However, vaccination history was associated with 94% (OR 0.06) lower odds of developing severe COVID-19 compared to those without a history of vaccination, regardless of the presence of associated risk factors. Conclusion: Lacking a history of vaccination and presenting any of the identified risk factors confer higher odds of developing severe forms of the disease.(AU)

Justificativa e Objetivos: Desde o seu aparecimento em 2019, foram identificados múltiplos fatores de risco para a apresentação de uma forma grave de COVID-19 e foram desenvolvidas diferentes vacinas para prevenir o aparecimento de manifestações graves. No entanto, apesar de um histórico de vacinação, alguns casos podem evoluir para complicações ou mesmo para a morte. O objetivo deste estudo foi determinar a força de associação entre a gravidade da COVID-19 e o histórico de vacinação em pacientes atendidos em um hospital público de referência na Cidade do México. Métodos: Estudo epidemiológico não-experimental, retrospectivo e analítico, de casos e controles. A população do estudo foram indivíduos atendidos em um hospital de concentração para atendimento à COVID-19 entre 1 de julho de 2021 e 30 de junho de 2022, na Cidade do México. Resultados: 132 participantes (44 casos e 88 controles) foram incluídos no estudo. Os fatores de risco mais fortemente associados à gravidade da COVID-19 foram idade superior ou igual a 60 anos, apresentar 22 respirações por minuto na primeira avaliação médica, pressão arterial sistólica superior ou igual a 140 milímetros de mercúrio e histórico de pelo menos uma comorbidade crônica. No entanto, histórico de vacinação foi associado a uma probabilidade 94% (OR 0,06) menor de desenvolver COVID-19 grave em comparação com aqueles sem histórico de vacinação, independentemente da presença de fatores de risco associados. Conclusão: A ausência de histórico de vacinação e a presença de algum dos fatores de risco identificados conferem maiores probabilidades de desenvolver formas graves da doença.(AU)

Justificación y Objetivos: Desde su aparición en 2019, se han identificado múltiples factores de riesgo para presentar una forma grave de COVID-19 y también se han desarrollado distintas vacunas que previenen la aparición de manifestaciones de gravedad. Sin embargo, a pesar del antecedente de vacunación, algunos casos se complican o incluso fallecen. El objetivo del este estudio fue determinar la fuerza de asociación entre la gravedad de la COVID-19 con el antecedente de vacunación en pacientes atendidos en un hospital público de referencia de la Ciudad de México. Métodos: Estudio epidemiológico no experimental, retrospectivo y analítico, de casos y controles. La población de estudio fueron personas atendidas en un hospital de concentración para la atención de COVID-19 entre el 1 de julio de 2021 y el 30 de junio de 2022 en la Ciudad de México. Resultados: 132 participantes (44 casos y 88 controles) fueron incluidos en el estudio. Los factores de riesgo más fuertemente asociados con la gravedad de la COVID-19 fueron la edad mayor o igual a 60 años, presentar 22 respiraciones por minuto en la primera valoración médica, tensión arterial sistólica mayor o igual a 140 milímetros de mercurio y el antecedente de al menos una comorbilidad crónica. No obstante, el antecedente de vacunación se asoció con 94% (RM 0.06) menos posibilidades de desarrollar COVID-19 grave con respecto a aquellos sin antecedente vacunal, independientemente de la presencia de los factores de riesgo asociados. Conclusión: carecer del antecedente de vacunación y presentar alguno de los factores de riesgo identificados confieren las mayores posibilidades de presentar formas graves de la enfermedad.(AU)

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Rotavirus A (RVA) is a major cause of acute gastroenteritis globally that is classically genotyped by its two immunodominant outer capsid proteins, VP7 (G-) and VP4 (P-). Recent evidence suggests that the reassortant equine-like G3P[8] strain played a substantial role in RVA transmission in Brazil since 2015. To understand its global emergence and dissemination in Brazilian territory, stool samples collected from 11 Brazilian states (n = 919) were genotyped by RT-qPCR and proceeded to sequence the VP7 gene (n = 102, 79 being newly generated) of the G3P[8] samples with pronounced viral loads. Our phylogenetic genotyping showed that G3P[8] became the dominant strain in Brazil between 2017 and 2020, with equine-like variants representing 75%-100% of VP7 samples in this period. A Bayesian discrete phylogeographic analysis strongly suggests that the equine-like G3P[8] strain originated in Asia during the early 2010s and subsequently spread to Europe, the Caribbean, and South America. Multiple introductions were detected in Brazil between 2014 and 2017, resulting in five national clusters. The reconstruction of the effective population size of the largest Brazilian cluster showed an expansion until 2017, followed by a plateau phase until 2019 and subsequent contraction. Our study also supports that most mutations fixed during equine-like G3P[8] evolution were synonymous, suggesting that adaptive evolution was not an important driving force during viral dissemination in humans, potentially increasing its susceptibility to acquired immunity. This research emphasizes the need for comprehensive rotavirus genomic surveillance that allows close monitoring of its ever-shifting composition and informs more effective public health policies.IMPORTANCEOur original article demonstrated the origin and spread in a short time of equine-like G3P[8] in Brazil and the world. Due to its segmented genome, it allows numerous mechanisms including genetic drift and reassortment contribute substantially to the genetic diversity of rotavirus. Although the effectiveness and increasing implementation of vaccination have not been questioned, a matter of concern is its impact on the emergence of escape mutants or even the spread of unusual strains of zoonotic transmission that could drive epidemic patterns worldwide. This research emphasizes the need for comprehensive rotavirus genomic surveillance, which could facilitate the formulation of public policies aimed at preventing and mitigating its transmission.

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The SARS-CoV-2 XBB is a group of highly immune-evasive lineages of the Omicron variant of concern that emerged by recombining BA.2-descendent lineages and spread worldwide during 2023. In this study, we combine SARS-CoV-2 genomic data (n = 11,065 sequences) with epidemiological data of severe acute respiratory infection (SARI) cases collected in Brazil between October 2022 and July 2023 to reconstruct the space-time dynamics and epidemiologic impact of XBB dissemination in the country. Our analyses revealed that the introduction and local emergence of lineages carrying convergent mutations within the Spike protein, especially F486P, F456L, and L455F, propelled the spread of XBB* lineages in Brazil. The average relative instantaneous reproduction numbers of XBB* + F486P, XBB* + F486P + F456L, and XBB* + F486P + F456L + L455F lineages in Brazil were estimated to be 1.24, 1.33, and 1.48 higher than that of other co-circulating lineages (mainly BQ.1*/BE*), respectively. Despite such a growth advantage, the dissemination of these XBB* lineages had a reduced impact on Brazil's epidemiological scenario concerning previous Omicron subvariants. The peak number of SARI cases from SARS-CoV-2 during the XBB wave was approximately 90%, 80%, and 70% lower than that observed during the previous BA.1*, BA.5*, and BQ.1* waves, respectively. These findings revealed the emergence of multiple XBB lineages with progressively increasing growth advantage, yet with relatively limited epidemiological impact in Brazil throughout 2023. The XBB* + F486P + F456L + L455F lineages stand out for their heightened transmissibility, warranting close monitoring in the months ahead. IMPORTANCE: Brazil was one the most affected countries by the SARS-CoV-2 pandemic, with more than 700,000 deaths by mid-2023. This study reconstructs the dissemination of the virus in the country in the first half of 2023, a period characterized by the dissemination of descendants of XBB.1, a recombinant of Omicron BA.2 lineages evolved in late 2022. The analysis supports that XBB dissemination was marked by the continuous emergence of indigenous lineages bearing similar mutations in key sites of their Spike protein, a process followed by continuous increments in transmissibility, and without repercussions in the incidence of severe cases. Thus, the results suggest that the epidemiological impact of the spread of a SARS-CoV-2 variant is influenced by an intricate interplay of factors that extend beyond the virus's transmissibility alone. The study also underlines the need for SARS-CoV-2 genomic surveillance that allows the monitoring of its ever-shifting composition.

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Latin America and Caribbean (LAC) regions were an important epicenter of the COVID-19 pandemic and SARS-CoV-2 evolution. Through the COVID-19 Genomic Surveillance Regional Network (COVIGEN), LAC countries produced an important number of genomic sequencing data that made possible an enhanced SARS-CoV-2 genomic surveillance capacity in the Americas, paving the way for characterization of emerging variants and helping to guide the public health response. In this study we analyzed approximately 300,000 SARS-CoV-2 sequences generated between February 2020 and March 2022 by multiple genomic surveillance efforts in LAC and reconstructed the diffusion patterns of the main variants of concern (VOCs) and of interest (VOIs) possibly originated in the Region. Our phylogenetic analysis revealed that the spread of variants Gamma, Lambda and Mu reflects human mobility patterns due to variations of international air passenger transportation and gradual lifting of social distance measures previously implemented in countries. Our results highlight the potential of genetic data to reconstruct viral spread and unveil preferential routes of viral migrations that are shaped by human mobility patterns.

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BACKGROUND: Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4+ T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences. OBJECTIVES: To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs. METHODS: We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity. FINDINGS: Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population. MAIN CONCLUSIONS: These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir's reseeding and low, but measurable, viral evolution despite undetectable viremia.

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We characterized 3 autochthonous dengue virus serotype 3 cases and 1 imported case from 2 states in the North and South Regions of Brazil, 15 years after Brazil's last outbreak involving this serotype. We also identified a new Asian lineage recently introduced into the Americas, raising concerns about future outbreaks.

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The SARS-CoV-2 variants of concern (VOCs) Delta and Omicron spread globally during mid and late 2021, respectively. In this study, we compare the dissemination dynamics of these VOCs in the Amazonas state, one of Brazil's most heavily affected regions. We sequenced the virus genome from 4128 patients collected in Amazonas between July 1st, 2021, and January 31st, 2022, and investigated the viral dynamics using a phylodynamic approach. The VOCs Delta and Omicron BA.1 displayed similar patterns of phylogeographic spread but different epidemic dynamics. The replacement of Gamma by Delta was gradual and occurred without an upsurge of COVID-19 cases, while the rise of Omicron BA.1 was extremely fast and fueled a sharp increase in cases. Thus, the dissemination dynamics and population-level impact of new SARS-CoV-2 variants introduced in the Amazonian population after mid-2021, a setting with high levels of acquired immunity, greatly vary according to their viral phenotype.

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BACKGROUND Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4+ T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences. OBJECTIVES To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs. METHODS We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity. FINDINGS Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population. MAIN CONCLUSIONS These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir's reseeding and low, but measurable, viral evolution despite undetectable viremia.

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Dengue virus serotype 2, genotype Cosmopolitan (DENV-2-GII), is one of the most widespread DENV strains globally. In the USA, DENV-2 epidemics have been dominated by DENV-2 genotype Asian-American (DENV-2-GIII), and the first cases of DENV-2-GII were only described in 2019, in Peru, and in 2021 in Brazil. To gain new information about the circulation of DENV-2-GII in Brazil, we sequenced 237 DENV-2 confirmed cases sampled between March 2021 and March 2023 and revealed that DENV-2-GII is already present in all geographic regions of Brazil. The phylogeographic analysis inferred that DENV-2-GII was introduced at least four times in Brazil, between May 2020 and August 2022, generating multiple clades that spread throughout the country with different success. Despite multiple introductions of DENV-2-GII, analysis of the country-wide laboratory surveillance data showed that the Brazilian dengue epidemic in 2022 was dominated by DENV-1 in most states. We hypothesize that massive circulation of DENV-2-GIII in previous years in Brazil might have created a population immune barrier against symptomatic homotypic reinfections by DENV-2-GII, leading to sustained cryptic circulation in asymptomatic cases and localized outbreaks of this new genotype. In summary, our study stresses the importance of arboviral genomic surveillance to close monitoring and better understanding the potential impact of DENV-2-GII in the coming years.

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The study of HIV-1 transmission networks inferred from viral genetic data can be used to clarify important factors about the dynamics of HIV-1 transmission, such as network growth rate and demographic composition. In Brazil, HIV transmission has been stable since the early 2000s and the study of transmission clusters can provide valuable data to understand the drivers of virus spread. In this work, we analyzed a nation-wide database of approximately 53,000 HIV-1 nucleotide pol sequences sampled from genotyped patients from 2008-2017. Phylogenetic trees were reconstructed for the HIV-1 subtypes B, C and F1 in Brazil and transmission clusters were inferred by applying genetic distances thresholds of 1.5%, 3.0% and 4.5%, as well as high (>0.9) cluster statistical support. An odds ratio test revealed that young men (15-24 years) and individuals with more years of education presented higher odds to cluster. The assortativity coefficient revealed that individuals with similar demographic features tended to cluster together, with emphasis on features, such as place of residence and age. We also observed that assortativity weakens as the genetic distance threshold increases. Our results indicate that the phylogenetic clusters identified here are likely representative of the contact networks that shape HIV transmission, and this is a valuable tool even in sites with low sampling density, such as Brazil.

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