Retrospective Analysis of the SARS-CoV-2 Infection Profile in COVID-19 Positive Patients in Vitoria da Conquista, Northeast Brazil.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is responsible for causing Coronavirus Disease-2019 (COVID-19), a heterogeneous clinical condition that manifests varying symptom severity according to the demographic profile of the studied population. While many studies have focused on the spread of COVID-19 in large urban centers in Brazil, few have evaluated medium or small cities in the Northeast region. The aims of this study were: (i) to identify risk factors for mortality from SARS-CoV-2 infection, (ii) to evaluate the gene expression patterns of key immune response pathways using nasopharyngeal swabs of COVID-19 patients, and (iii) to identify the circulating SARS-CoV-2 variants in the residents of a medium-sized city in Northeast Brazil. A total of 783 patients infected with SARS-CoV-2 between May 2020 and August 2021 were included in this study. Clinical-epidemiological data from patients who died and those who survived were compared. Patients were also retrospectively divided into three groups based on disease severity: asymptomatic, mild, and moderate/severe. Samples were added to a qPCR array for analyses of 84 genes involved with immune response pathways and sequenced using the Oxford Nanopore MinION technology. Having pre-existing comorbidity; being male; having cardiovascular disease, diabetes, and/or chronic obstructive pulmonary disease; and PCR cycle threshold (Ct) values under 22 were identified as risk factors for mortality. Analysis of the expression profiles of inflammatory pathway genes showed that the greater the infection severity, the greater the activation of inflammatory pathways, triggering the cytokine storm and downregulating anti-inflammatory pathways. Viral genome analysis revealed the circulation of multiple lineages, such as B.1, B.1.1.28, Alpha, and Gamma, suggesting that multiple introduction events had occurred over time. This study's findings help identify the specific strains and increase our understanding of the true state of local health. In addition, our data demonstrate that epidemiological and genomic surveillance together can help formulate public health strategies to guide governmental actions.

Transmission dynamics and molecular characterization of HIV-1 epidemic among therapeutic failure patients in Santa Catarina state, southern Brazil.

The HIV-1 epidemic in southern Brazil is mostly caused by subtype C, which contrasts the dominance of subtype B in the other regions of the country. Santa Catarina (SC), although the smallest state in the southern region, presents one of the highest incidences and mortality rates in Brazil due to AIDS. This work investigated the HIV-1 molecular diversity and phylogenetic transmission networks in SC state by analyzing a database of 3070 sequences of the national genotyping service. HIV-1C proved to be the most frequent subtype, with a significant increase in prevalence over time. HIV-1B was observed to be associated with highly educated men, suggesting a compartmentalization from other subtypes. Such observation was confirmed by the high frequency of HIV-1B circulating in MSM transmission networks. Identified transmission clusters were majority composed by individuals living up to 25 km away and interstate linkages were mainly between southern neighbor states. In general, individuals between 25 and 40 years old and sequences sampled after 2014 were more likely to be in transmission chains, in agreement with the universal treatment protocol launched in 2014. The present study brings new insights about HIV-1 transmission dynamics in southern Brazil.

Spatiotemporal and demographic history of the HIV-1 circulating recombinant form CRF31_BC in Brazil.

CRF31_BC is an HIVs-1 recombinant form very prevalent in the southernmost capital city of Brazil, Porto Alegre. Recent studies have been describing a growing number of cases of infection by CRF31_BC in other Brazilian cities and countries, suggesting a process of expansion of this strain. Aiming to describe the city of origin, dispersion routes and demographic history of CRF31_BC, this study analyzed all HIV-1 CRF31_BC and Brazilian BC mosaic publicly available sequences. CRF31_BC classification was performed by bootscanning and tree reconstruction methods. Bayesian phylogeographic and phylodynamic model approaches were used to reconstruct the spatiotemporal and demographic history of 95 sequences identified as CRF31_BC-like. Porto Alegre was estimated to be the origin and center of the dispersion of the CRF31_BC for most of the analyzed locations. However, some viral transitions independent from Porto Alegre were observed in other cities from the Rio Grande do Sul state and also in other Brazilian states. The estimated CRF31_BC epidemic growth rate was similar to subtype C and B in Brazil. Our findings suggest that CRF31_BC, although mostly prevalent in south region, is circulating nation-wide with some localities presenting autochthonous transmissions.

Sedating effects of Humulus lupulus L. extracts.

It was the aim of the study to check ethanolic and CO2 extracts from Humulus lupulus for sedating activity. Both preparations reduced the spontaneous locomotor activity, increased the ketamine-induced sleeping time and reduced body temperature, confirming a central sedating effect. No indications of anxiolytic activity were found in the elevated plus maze test for any of the test preparations. This sedating activity could be attributed to three categories of constituents of lipophilic hops extracts. Though the alpha-bitter acids proved to the be most active constituents, the beta-bitter acids and the hop oil clearly contributed to the sedating activity of lipophilic Humulus extracts.

Flavonoids of St. John's Wort reduce HPA axis function in the rat.

A common biological alteration in patients with major depression is the activation of the hypothalamic-pituitary-adrenal (HPA) axis, manifested as hypersecretion of adrenocorticotropic hormone (ACTH) and cortisol. The hyperactivity of the HPA axis in depressed patients can be corrected during clinically effective therapy with standard antidepressant drugs such as imipramine, indicating that the HPA axis may be an important target for antidepressant action. We previously showed that a methanolic extract of St. John's Wort (SJW) and hypericin, one of its active constituents, both have delayed effects on the expression of genes that are involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis , whereas the phloroglucinol derivative hyperforin was inactive in the same model . Since flavonoids of SJW are also discussed as active constituents it was of interest to determine whether these compounds can modulate HPA axis function. Imipramine (15 mg/kg), hypericin (0.2 mg/kg), hyperoside (0.6 mg/kg), isoquercitrin (0.6 mg/kg) and miquelianin (0.6 mg/kg) given daily by gavage for two weeks significantly down-regulated circulating plasma levels of ACTH and corticosterone by 40 - 70 %. However, none of the compounds tested had an effect on plasma ACTH and corticosterone levels after chronic treatment (daily gavage for 8 weeks). Our data suggest that besides hypericin, flavonoids of SJW play an important role in the modulation of HPA axis function. Furthermore, the results support the hypothesis that flavonoids are involved in the antidepressant effects of SJW.