MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study.

BACKGROUND: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. OBJECTIVE: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. METHODS: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. RESULTS: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. CONCLUSIONS: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.

Seroprevalence and indexes of IgG antibodies for SARS-CoV-2 infection among People Living With HIV, tuberculosis patients and healthcare workers, in Salvador, Brazil.

INTRODUCTION: COVID-19 can trigger different clinical presentations in distinct population groups, some of which are considered at higher risk of SARS-CoV-2 infection. Little is known about the susceptibility of certain populations to the infection. OBJECTIVES: We aimed to determine the prevalence of COVID-19 among People Living With HIV/AIDS (PLWH) attending a tertiary public hospital in Salvador, Brazil, patients with active pulmonary tuberculosis and Hospital's Healthcare Workers (HCW), and to compare their SARS-CoV-2 antibody levels. METHODS: In this observational study we included 2294 participants from June 9, 2020 to August 10, 2021. IgG SARS-CoV-2 antibodies from all participants (275 PLWH, 42 with active tuberculosis and 1977 healthcare workers) were measured. Prevalence of COVID-19 and antibodies indexes were compared across groups. RESULTS: We detected a higher prevalence of COVID-19 in patients with active tuberculosis (42.9%) than in PLWH (22.5%) or HCW (11.7%). Previously vaccinated participants with a COVID-19 history had median higher IgG antibody indexes (8.2; IQR: 5.5‒10) than those vaccinated who did not have COVID-19 until the time of this study (4.1; IQR: 1.6‒6.2, p < 0.001). CONCLUSION: Prevalence of previous SARS-CoV-2 infection was higher among tuberculosis patients than that found in HCW and PLWH, but antibodies levels were similar across groups.

Physiotherapeutic treatment associated with the pain neuroscience education for patients with chronic non-specific low back pain-single-blind randomized pilot clinical trial.

OBJECTIVES: Pain Neuroscience Education (PNE) shows improvement in pain and functional capacity in patients with chronic low back pain (CLBP). Therefore, the study aimed to verify if the physiotherapeutic treatment associated with PNE decreases the functional disability of patients with nonspecific CLBP. METHODS: Forty patients were clinically evaluated and answered the following questionnaires: Brief pain inventory, Central Sensitization Inventory (CSI), Roland-Morris disability questionnaire, pain catastrophizing scale, Tampa scale of kinesiophobia, hospital anxiety, and depression scale, SF6D quality of life questionnaire and performed quantitative sensory tests (QSTs). Afterward, they were randomly divided into the intervention group (IG, n=20) and the control group (CG, n=20). Both performed kinesiotherapy exercises twice a week for 6 weeks. The IG received 3 individual PNE sessions and answered the pain neurophysiology questionnaire. RESULTS: IG showed significant improvement for all variables analyzed (p<0.001). The association decreased the kinesiophobia (estimated difference between CG-IG means: 7.6-95% CI: 2.3-12.9) (p=0.006). In the lumbar paravertebral region (CG and IG), there was a statistical difference in the intensity of CLBP in the QSTs (p<0.05). CONCLUSION: The association showed better results compared to only therapeutic exercises to reduce kinesiophobia and change the perception of pain intensity in the lumbar region.

Presença de desertos alimentares em um distrito sanitário de uma capital brasileira: um estudo descritivo e exploratório sobre a distribuição espacial de estabelecimentos comerciais de alimentos / Food deserts in a health district of a Brazilian capital: a descriptive and exploratory study on the spatial distribution of commercial food establishments

Introdução: O ambiente alimentar que a comunidade está inserida pode influenciar, positiva ou negativamente no acesso à alimentação de qualidade e consequentemente na sua saúde. Objetivo: Identificar a presença de desertos alimentares em um distrito sanitário de uma capital brasileira. Métodos: Estudo descritivo, transversal e exploratório, utilizando dados secundários de diferentes fontes institucionais para mapear a distribuição espacial de estabelecimentos de comercialização de alimentos: restaurantes, padarias, supermercados, minimercados/mercearias, hortifrutigranjeiros, vendedores ambulantes e lanchonetes/fastfood. Os estabelecimentos foram agrupados nas categorias in natura, ultraprocessados e mistos, de acordo com a predominância do tipo de alimentos comercializados. Para a análise, a densidade de estabelecimentos in natura juntamente com os mistos por mil habitantes (usuários cadastrados nos centros de saúde) foram calculadas.  Resultados: Foram investigados 111 estabelecimentos, sendo 20% que comercializavam alimentos in natura (saudáveis), 27% alimentos ultraprocessados (não saudáveis) e 53% considerados mistos. Conclusões: Foram observadas áreas que podem ser consideradas desertos alimentares, locais onde há pouca (ou ausência) de oferta de alimentos in natura, e por consequência dificultando o acesso a alimentos saudáveis.

Introduction: The communities' food environment can positively or negatively influence access to quality food and consequently, people's health. Objective: Identify the presence of food deserts in a health district of a Brazilian capital. Methods: Descriptive, cross-sectional and exploratory study, using secondary data from different institutional sources to map the spatial distribution of food establishments such as restaurants, bakeries, supermarkets, minimarkets/grocery stores, fruit and vegetable stores, street vendors and cafeterias/fast food. The establishments were grouped into fresh, ultra-processed and mixed food categories, according to the predominance of the type of food offered. For the purpose of analysis, the density of fresh food establishments together with mixed food establishments per thousand inhabitants (as registered in the health centers) was calculated.  Results: A total of 111 establishments were investigated, 20% selling fresh foods (healthy), 27% ultra-processed foods (unhealthy) and 53% considered mixed food sellers. Conclusions: Areas that can be considered food deserts were found, i.e. places where there is little (or absence) of fresh food supply, and consequently making access to healthy foods difficult.

Seroprevalence and indexes of IgG antibodies for SARS-CoV-2 infection among People Living With HIV, tuberculosis patients and healthcare workers, in Salvador, Brazil

ABSTRACT Introduction: COVID-19 can trigger different clinical presentations in distinct population groups, some of which are considered at higher risk of SARS-CoV-2 infection. Little is known about the susceptibility of certain populations to the infection. Objectives: We aimed to determine the prevalence of COVID-19 among People Living With HIV/AIDS (PLWH) attending a tertiary public hospital in Salvador, Brazil, patients with active pulmonary tuberculosis and Hospital's Healthcare Workers (HCW), and to compare their SARS-CoV-2 antibody levels. Methods: In this observational study we included 2294 participants from June 9, 2020 to August 10, 2021. IgG SARS-CoV-2 antibodies from all participants (275 PLWH, 42 with active tuberculosis and 1977 healthcare workers) were measured. Prevalence of COVID-19 and antibodies indexes were compared across groups. Results: We detected a higher prevalence of COVID-19 in patients with active tuberculosis (42.9%) than in PLWH (22.5%) or HCW (11.7%). Previously vaccinated participants with a COVID-19 history had median higher IgG antibody indexes (8.2; IQR: 5.5-10) than those vaccinated who did not have COVID-19 until the time of this study (4.1; IQR: 1.6-6.2, p < 0.001). Conclusion: Prevalence of previous SARS-CoV-2 infection was higher among tuberculosis patients than that found in HCW and PLWH, but antibodies levels were similar across groups.

A Simplified Sanger Sequencing Method for Detection of Relevant SARS-CoV-2 Variants.

Molecular surveillance of the new coronavirus through new genomic sequencing technologies revealed the circulation of important variants of SARS-CoV-2. Sanger sequencing has been useful in identifying important variants of SARS-CoV-2 without the need for whole-genome sequencing. A sequencing protocol was constructed to cover a region of 1000 base pairs, from a 1120 bp product generated after a two-step RT-PCR assay in samples positive for SARS-CoV-2. Consensus sequence construction and mutation identification were performed. Of all 103 samples sequenced, 69 contained relevant variants represented by 20 BA.1, 13 delta, 22 gamma, and 14 zeta, identified between June 2020 and February 2022. All sequences found were aligned with representative sequences of the variants. Using the Sanger sequencing methodology, we were able to develop a more accessible protocol to assist viral surveillance with a more accessible platform.

Frequent Infection of Cats With SARS-CoV-2 Irrespective of Pre-Existing Enzootic Coronavirus Immunity, Brazil 2020.

Carnivores such as cats and minks are highly susceptible to SARS-CoV-2. Brazil is a global COVID-19 hot spot and several cases of human-to-cat transmission have been documented. We investigated the spread of SARS-CoV-2 by testing 547 domestic cats sampled between July-November 2020 from seven states in southern, southeastern, and northeastern Brazil. Moreover, we investigated whether immune responses elicited by enzootic coronaviruses affect SARS-CoV-2 infection in cats. We found infection with significantly higher neutralizing antibody titers against the Gamma variant of concern, endemic in Brazil during 2020, than against an early SARS-CoV-2 B.1 isolate (p<0.0001), validating the use of Gamma for further testing. The overall SARS-CoV-2 seroprevalence in Brazilian cats during late 2020 validated by plaque reduction neutralization test (PRNT90) was 7.3% (95% CI, 5.3-9.8). There was no significant difference in SARS-CoV-2 seroprevalence in cats between Brazilian states, suggesting homogeneous infection levels ranging from 4.6% (95% CI, 2.2-8.4) to 11.4% (95% CI, 6.7-17.4; p=0.4438). Seroprevalence of the prototypic cat coronavirus Feline coronavirus (FCoV) in a PRNT90 was high at 33.3% (95% CI, 24.9-42.5) and seroprevalence of Bovine coronavirus (BCoV) was low at 1.7% (95% CI, 0.2-5.9) in a PRNT90. Neutralizing antibody titers were significantly lower for FCoV than for SARS-CoV-2 (p=0.0001), consistent with relatively more recent infection of cats with SARS-CoV-2. Neither the magnitude of SARS-CoV-2 antibody titers (p=0.6390), nor SARS-CoV-2 infection status were affected by FCoV serostatus (p=0.8863). Our data suggest that pre-existing immunity against enzootic coronaviruses neither prevents, nor enhances SARS-CoV-2 infection in cats. High SARS-CoV-2 seroprevalence already during the first year of the pandemic substantiates frequent infection of domestic cats and raises concerns on potential SARS-CoV-2 mutations escaping human immunity upon spillback.

Candida albicans commensalism in the oral mucosa is favoured by limited virulence and metabolic adaptation.

As part of the human microbiota, the fungus Candida albicans colonizes the oral cavity and other mucosal surfaces of the human body. Commensalism is tightly controlled by complex interactions of the fungus and the host to preclude fungal elimination but also fungal overgrowth and invasion, which can result in disease. As such, defects in antifungal T cell immunity render individuals susceptible to oral thrush due to interrupted immunosurveillance of the oral mucosa. The factors that promote commensalism and ensure persistence of C. albicans in a fully immunocompetent host remain less clear. Using an experimental model of C. albicans oral colonization in mice we explored fungal determinants of commensalism in the oral cavity. Transcript profiling of the oral isolate 101 in the murine tongue tissue revealed a characteristic metabolic profile tailored to the nutrient poor conditions in the stratum corneum of the epithelium where the fungus resides. Metabolic adaptation of isolate 101 was also reflected in enhanced nutrient acquisition when grown on oral mucosa substrates. Persistent colonization of the oral mucosa by C. albicans also correlated inversely with the capacity of the fungus to induce epithelial cell damage and to elicit an inflammatory response. Here we show that these immune evasive properties of isolate 101 are explained by a strong attenuation of a number of virulence genes, including those linked to filamentation. De-repression of the hyphal program by deletion or conditional repression of NRG1 abolished the commensal behaviour of isolate 101, thereby establishing a central role of this factor in the commensal lifestyle of C. albicans in the oral niche of the host.

Chlorhexidine mouthwash reduces the salivary viral load of SARS-CoV-2: A randomized clinical trial.

OBJECTIVES: This study aimed to evaluate the effect of 0.12% chlorhexidine gluconate on the salivary load of SARS-CoV-2. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was performed on 100 participants positive for SARS-CoV-2. In the test group (n = 50), volunteers gargled with a mouthwash containing 15 ml of 0.12% chlorhexidine gluconate for 1 min, while the control group (n = 50) used a placebo. Saliva samples were obtained before (baseline) and 5 and 60 min after using the solutions. Real-time reverse transcription polymerase chain reaction assays (qRT-PCR) were carried out and the cycle threshold (Ct) was computed. The chi-square test and t-test were used for group comparison (p ≤ 0.05). RESULTS: The differences in Ct values between the 5-min evaluation and baseline (test group: 2.19 ± 4.30; control: -0.40 ± 3.87, p = 0.002) and between 60 min and baseline (test group: 2.45 ± 3.88; control: 0.76 ± 4.41, p = 0.05) were significantly greater in the test group, revealing a reduction of viral load. Furthermore, there was a reduction in the load of SARS-CoV-2 in 72% of the volunteers using chlorhexidine versus 30% in the control group (p = 0.001). CONCLUSIONS: Chlorhexidine gluconate (0.12%) was effective in reducing salivary SARS-CoV-2 load for at least 60 min.

Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response.

BACKGROUND: Over-the-counter use of ivermectin amongst other drugs as SARS-CoV-2 treatment has been increasingly common, despite the lack of evidence on its clinical efficacy. OBJECTIVE: To evaluate the effect of ivermectin use on production of antibodies against SARS-CoV-2 in health care workers (HCW) diagnosed with COVID-19 and of Th1/Th2 cytokines by stimulated peripheral blood mononuclear cells of the same cohort (PBMCs). METHODS: This cross-sectional study evaluated seroconversion and neutralizing antibodies production in HCW at Complexo Hospitalar Universitário Professor Edgard Santos (Salvador, Brazil), diagnosed with COVID-19 from May to July, 2020, as well as in vitro production of antibody against SARS-CoV-2 and Th1/Th2 cytokines. Analyses were performed between December 2020 and February 2021. Participants were stratified according to the use of ivermectin (≤ 1 dose vs. multiple doses) for treatment of COVID-19. RESULTS: 45 HCW were included (62% women). Mean age was 39 years, and disease severity was similar across groups. Neutralizing antibodies were detected less frequently in multiple doses (70%) vs. ≤ 1 dose (97%) groups, p = 0.02). PBMCs of patients in multiple doses group also were less likely to produce antibodies against SARS-CoV-2 following in vitro stimulation with purified spike protein in comparison with patients in ≤ 1 dose group (p < 0.001). PBMC´s production of Th1/Th2 cytokines levels was similar across groups. Abdominal pain (15% vs 46%, p = 0.04), diarrhea (21% vs. 55%, p = 0.05) and taste perversion (0% vs. 18%, p = 0.05) were more frequently reported by participants that used multiple doses of ivermectin. CONCLUSIONS: Although there was no evidence for differential disease severity upon ivermectin use for treatment of COVID-19 it was associated with more gastro-intestinal side-effects and impairment of anti-SARS-CoV2 antibodies production, in a dose dependent manner. This potentially impacts the effectiveness of immune response and the risk of reinfection and warrants additional studies for clarifying the mechanisms and consequences of such immunomodulatory effects.