Metaviromic reveals the dynamics and diversity of the virosphere in wastewater samples from Natal, Brazil.

The COVID-19 pandemic underscored the significance of omics technology and Wastewater-Based Epidemiology for epidemic preparedness. This study investigates the virosphere in wastewater samples from Natal (Brazil), aiming to understand its structure, relationships, and potential. Metaviromic analysis was used on DNA and RNA from weekly samples collected over a year (June/2021 to May/2022) from three wastewater treatment plants. The virosphere showed stability, particularly in viruses infecting microorganisms and plants. However, an alternation of representatives of viruses that infect animals has been observed. Among the most abundant viruses infecting microorganisms are genera associated with the bacterial genera Escherichia, Pseudomonas, and Caulobacte. Regarding the viruses infecting plants, Sobemovirus and Tobamovirus are the most abundant genera. Odontoglossum ringspot virus was identified as a possible RNA virus biomarker. Among DNA viruses infecting animals, genera Bocaparvovirus and Mastadenovirus are the most prevalent. Intriguingly, some Poxviridae family members were observed in the samples. Co-occurrence network analysis identified potential biomarkers like Volepox virus, Anatid herpesvirus 1, and Caviid herpesvirus 2. Among RNA viruses affecting animals, Mamastrovirus, Rotavirus, and Norovirus genera were the most abundant pathogens. Furthermore, members of the Coronaviridae family exhibited a high degree of centrality values in the co-occurrence network, even connecting with unclassified viruses. The study emphasizes the importance of research in understanding the roles of unclassified viruses. In addition, we observed an association between Coronaviridae reads, rainfall, and the number of reported COVID-19 cases. Our study highlights the diversity and complexity of the viral community in wastewater and the need for research to understand better the ecological roles unclassified viruses play. Such advances will significantly contribute to our preparedness and response to future viral threats. Furthermore, our study contributes to knowledge of virosphere dynamics, offering insights that can contribute to the direction of future public health policies and interventions.

Integrated analysis of RNA-seq datasets reveals novel targets and regulators of COVID-19 severity.

During the COVID-19 pandemic, RNA-seq datasets were produced to investigate the virus-host relationship. However, much of these data remains underexplored. To improve the search for molecular targets and biomarkers, we performed an integrated analysis of multiple RNA-seq datasets, expanding the cohort and including patients from different countries, encompassing severe and mild COVID-19 patients. Our analysis revealed that severe COVID-19 patients exhibit overexpression of genes coding for proteins of extracellular exosomes, endomembrane system, and neutrophil granules (e.g., S100A9, LY96, and RAB1B), which may play an essential role in the cellular response to infection. Concurrently, these patients exhibit down-regulation of genes encoding components of the T cell receptor complex and nucleolus, including TP53, IL2RB, and NCL Finally, SPI1 may emerge as a central transcriptional factor associated with the up-regulated genes, whereas TP53, MYC, and MAX were associated with the down-regulated genes during COVID-19. This study identified targets and transcriptional factors, lighting on the molecular pathophysiology of syndrome coronavirus 2 infection.