SARS-CoV-2 Lineage P.4 Detection in Southeast Brazil: A Retrospective Genomic and Clinical Overview

São Paulo state has been the epicenter of the Coronavirus Disease 2019 (COVID-19) in Brazil, ranking first by state with over six million reported cases. In February 2021, the P.4 lineage was reported in 21 cities across the state by public health authorities due to the L452R mutation. Here, by analyzing 17,304 genome sequences of SARS-CoV-2 sampled between February and August of 2021 in 476 distinct cities in São Paulo, we assess the transmission dynamics of the P.4 lineage and other SARS-CoV-2 variants that were, at the time of the study, co-circulating in the state. Additionally, clinical parameters from the city of Araras, São Paulo (N = 251) were considered to estimate the potential risk and mortality rate associated with the P.4 lineage since its higher prevalence was observed in that city. Our data suggest a low frequency (0.55%) of the P.4 lineage across the state, with the gamma variant being the dominant form in all regions (90%) at that time. Furthermore, no evidence of increased transmissibility and disease severity related to the P.4 lineage was observed. The displacement through the time of different lineages in São Paulo highlights how challenging genomic surveillance appears to track the emergence of new SARS-CoV-2 lineages, which could better guide the implementation of control measures. [ FROM AUTHOR]

A comparative overview of SARS-CoV-2 and its variants of concern.

In December 2019, the severe acute respiratory syndrome 2 (SARS-CoV-2) coronavirus outbreak began in Wuhan, China, and quickly spread to practically every corner of the globe, killing millions of people. SARS-CoV-2 produced numerous variants, five of which have been identified as variants of concern (VOC) by the World Health Organization (WHO) (Alpha, Beta, Gamma, Delta, and Omicron). We conducted a comparative epidemiological analysis of SARS-CoV-2 and its VOC in this paper. We compared the effects of various spike (S) protein mutations in SARS-CoV-2 and its VOC on transmissibility, illness severity, hospitalization risk, fatality rate, immunological evasion, and vaccine efficacy in this review. We also looked into the clinical characteristics of patients infected with SARS-CoV-2 and its VOC.

Data-driven identification of SARS-CoV-2 subpopulations using PhenoGraph and binary-coded genomic data.

For epidemic prevention and control, the identification of SARS-CoV-2 subpopulations sharing similar micro-epidemiological patterns and evolutionary histories is necessary for a more targeted investigation into the links among COVID-19 outbreaks caused by SARS-CoV-2 with similar genetic backgrounds. Genomic sequencing analysis has demonstrated the ability to uncover viral genetic diversity. However, an objective analysis is necessary for the identification of SARS-CoV-2 subpopulations. Herein, we detected all the mutations in 186 682 SARS-CoV-2 isolates. We found that the GC content of the SARS-CoV-2 genome had evolved to be lower, which may be conducive to viral spread, and the frameshift mutation was rare in the global population. Next, we encoded the genomic mutations in binary form and used an unsupervised learning classifier, namely PhenoGraph, to classify this information. Consequently, PhenoGraph successfully identified 303 SARS-CoV-2 subpopulations, and we found that the PhenoGraph classification was consistent with, but more detailed and precise than the known GISAID clades (S, L, V, G, GH, GR, GV and O). By the change trend analysis, we found that the growth rate of SARS-CoV-2 diversity has slowed down significantly. We also analyzed the temporal, spatial and phylogenetic relationships among the subpopulations and revealed the evolutionary trajectory of SARS-CoV-2 to a certain extent. Hence, our results provide a better understanding of the patterns and trends in the genomic evolution and epidemiology of SARS-CoV-2.

Integrated gut virome and bacteriome dynamics in COVID-19 patients.

SARS-CoV-2 is the cause of the current global pandemic of COVID-19; this virus infects multiple organs, such as the lungs and gastrointestinal tract. The microbiome in these organs, including the bacteriome and virome, responds to infection and might also influence disease progression and treatment outcome. In a cohort of 13 COVID-19 patients in Beijing, China, we observed that the gut virome and bacteriome in the COVID-19 patients were notably different from those of five healthy controls. We identified a bacterial dysbiosis signature by observing reduced diversity and viral shifts in patients, and among the patients, the bacterial/viral compositions were different between patients of different severities, although these differences are not entirely distinguishable from the effect of antibiotics. Severe cases of COVID-19 exhibited a greater abundance of opportunistic pathogens but were depleted for butyrate-producing groups of bacteria compared with mild to moderate cases. We replicated our findings in a mouse COVID-19 model, confirmed virome differences and bacteriome dysbiosis due to SARS-CoV-2 infection, and observed that immune/infection-related genes were differentially expressed in gut epithelial cells during infection, possibly explaining the virome and bacteriome dynamics. Our results suggest that the components of the microbiome, including the bacteriome and virome, are affected by SARS-CoV-2 infections, while their compositional signatures could reflect or even contribute to disease severity and recovery processes.

SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay.

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.