The effect of BCG vaccination on infection and antibody levels against SARS-CoV-2-The results of ProBCG: a multicenter randomized clinical trial in Brazil.

OBJECTIVES: Evatuate if Bacillus Calmette-Guérin (BCG) vaccine could be used as a tool against SARS-CoV-2 based on the concept of trained immunity. METHODS: A multicenter, double-blinded, randomized clinical trial recruited health care workers (HCWs) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCWs receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac or COVISHIELD) was analyzed. Cox proportional hazard and linear mixed effect modeling were used. RESULTS: A total of 264 volunteers were included for analysis (BCG = 134 and placebo = 130). The placebo group presented a COVID-19 cumulative incidence of 0.75% vs 0.52% of BCG. The Moreau strain also presented a higher incidence rate (1.60% × 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log (immunoglobulin G) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance. CONCLUSION: Our results suggest that BCG has a tendency of protection against SARS-CoV-2 and higher immunoglobulin G levels than placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941).

Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST.

SETTING: Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH). DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH. OBJECTIVE: To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers. DESIGN: This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used. RESULTS: The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses. CONCLUSION: Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p=0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.

Impact of systemic corticosteroids on the clinical course and outcomes of patients with severe community-acquired pneumonia: a cohort study.

INTRODUCTION: Our aim was to evaluate the impact of corticosteroids on clinical course and outcomes of patients with severe community-acquired pneumonia (CAP) requiring invasive mechanical ventilation. METHODS: This was a cohort study of patients with severe CAP from 2 intensive care units in tertiary hospitals in Brazil and Portugal. RESULTS: A total of 111 patients were included (median age, 69 years; 56% men; 34% hospital mortality). Corticosteroids were prescribed in 61 (55%) patients. Main indications for their use were bronchospasm (52.5%) and septic shock (36%). Mortality rate of patients treated with and without corticosteroids was comparable (29.5% vs 32%, P = .837). No significant differences were observed on clinical course from day 1 to day 7 as assessed by the Sequential Organ Failure Assessment score (P = .95). Furthermore, C-reactive protein declined similarly in both groups (P = .147). In a multivariate analysis, mortality was associated with older age and higher Acute Physiology and Chronic Health Evaluation II score. CONCLUSIONS: In patients with severe CAP requiring invasive mechanical ventilation, adjunctive therapy with corticosteroids did not influence intensive care unit and hospital mortality. In addition, no changes were observed on weaning from vasopressors, on recovery from organ failure/dysfunction as assessed by the Sequential Organ Failure Assessment score, as well as on C-reactive protein course.

Lung production of platelet-activating factor acetylhydrolase in oleic acid-induced acute lung injury.

Platelet-activating factor (PAF) is a proinflammatory mediator that plays a central role in acute lung injury (ALI). PAF- acetylhydrolases (PAF-AHs) terminate PAF's signals and regulate inflammation. In this study, we describe the kinetics of plasma and bronchoalveolar lavage (BAL) PAF-AH in the early phase of ALI. Six pigs with oleic acid induced ALI and two healthy controls were studied. Plasma and BAL samples were collected every 2h and immunohistochemical analysis of PAF-AH was performed in lung tissues. PAF-AH activity in BAL was increased at the end of the experiment (BAL PAF-AH Time 0=0.001+/-0.001 nmol/ml/min/g vs Time 6=0.031+/-0.018 nmol/ml/min/g, p=0.04) while plasma activity was not altered. We observed increased PAF-AH staining of macrophages and epithelial cells in the lungs of animals with ALI but not in healthy controls. Our data suggest that increases in PAF-AH levels are, in part, a result of alveolar production. PAF-AH may represent a modulatory strategy to counteract the excessive pro-inflammatory effects of PAF and PAF-like lipids in lung inflammation.

Distribution of immune cell subsets and cytokine-producing cells in the uterine cervix of human papillomavirus (HPV)-infected women: influence of HIV-1 coinfection.

The aim of this study was to characterize the immune system profile in the uterine cervix of 17 human papillomavirus (HPV)-infected women, compared with 17 whom were coinfected with HIV-1. Five histologically normal cervices in immunocompetent women were used as controls. HPV infection was associated with a marked increase in cells expressing interleukin (IL)-6, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha). Coinfection by HPV and HIV-1 led to decreased expression of IL-6, TNF-alpha, and IFN-gamma. However, coinfection led to increased numbers of cells expressing IL-4, IL-10, and IL-8. Compared with the histologically normal cervices, increased numbers of macrophages (CD68, RFD7) and T lymphocytes (CD4, CD8) were seen in HPV-infected cervices; coinfection with HIV-1 was associated with a higher number of CD8 cells and lower number of CD68 cells. HPV DNA localized exclusively to the dysplastic squamous cells, whereas HIV-1 RNA was detected mainly in CD68-positive stromal cells. In conclusion, this study shows differential expression of various cytokines and classes of inflammatory cells, relative to HIV-1 infection and HPV coinfection, which may relate to the risk of transmission of HIV-1 and increased risk of cervical cancer in these women.