Randomized clinical trial of BCG vaccine in patients with convalescent COVID-19: Clinical evolution, adverse events, and humoral immune response.

BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine may confer cross-protection against viral diseases in adults. This study evaluated BCG vaccine cross-protection in adults with convalescent coronavirus disease 2019 (COVID-19). METHOD: This was a multicenter, prospective, randomized, placebo-controlled, double-blind phase III study (ClinicalTrials.gov: NCT04369794). SETTING: University Community Health Center and Municipal Outpatient Center in South America. PATIENTS: a total of 378 adult patients with convalescent COVID-19 were included. INTERVENTION: single intradermal BCG vaccine (n = 183) and placebo (n = 195). MEASUREMENTS: the primary outcome was clinical evolution. Other outcomes included adverse events and humoral immune responses for up to 6 months. RESULTS: A significantly higher proportion of BCG patients with anosmia and ageusia recovered at the 6-week follow-up visit than placebo (anosmia: 83.1% vs. 68.7% healed, p = 0.043, number needed to treat [NNT] = 6.9; ageusia: 81.2% vs. 63.4% healed, p = 0.032, NNT = 5.6). BCG also prevented the appearance of ageusia in the following weeks: seven in 113 (6.2%) BCG recipients versus 19 in 126 (15.1%) placebos, p = 0.036, NNT = 11.2. BCG did not induce any severe or systemic adverse effects. The most common and expected adverse effects were local vaccine lesions, erythema (n = 152; 86.4%), and papules (n = 111; 63.1%). Anti-severe acute respiratory syndrome coronavirus 2 humoral response measured by N protein immunoglobulin G titer and seroneutralization by interacting with the angiotensin-converting enzyme 2 receptor suggest that the serum of BCG-injected patients may neutralize the virus at lower specificity; however, the results were not statistically significant. CONCLUSION: BCG vaccine is safe and offers cross-protection against COVID-19 with potential humoral response modulation. LIMITATIONS: No severely ill patients were included.

Clinical implications of single cell sequencing for bladder cancer.

Bladder cancer (BC) is the 10th most common cancer worldwide, with about 0.5 million reported new cases and about 0.2 million deaths per year. In this scoping review, we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines. We searched PubMed, CENTRAL, Embase, and supplemented with manual searches through the Scopus, and Web of Science for published studies until February 2023. We included original studies that used at least one single-cell technology to study bladder cancer. Forty-one publications were included in the review. Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy. Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples. The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level. Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management. This nascent tool can advance the early diagnosis, prognosis judgment, and targeted therapy of bladder cancer.

Increased expression of miR-320b in blood plasma of patients in response to SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recent research has demonstrated how epigenetic mechanisms regulate the host-virus interactions in COVID-19. It has also shown that microRNAs (miRNAs) are one of the three fundamental mechanisms of the epigenetic regulation of gene expression and play an important role in viral infections. A pilot study published by our research group identified, through next-generation sequencing (NGS), that miR-4433b-5p, miR-320b, and miR-16-2-3p are differentially expressed between patients with COVID-19 and controls. Thus, the objectives of this study were to validate the expression of these miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR) and to perform in silico analyses. Patients with COVID-19 (n = 90) and healthy volunteers (n = 40) were recruited. MiRNAs were extracted from plasma samples and validated using qRT-PCR. In addition, in silico analyses were performed using mirPath v.3 software. MiR-320b was the only miRNA upregulated in the case group com-pared to the control group. The in silico analyses indicated the role of miR-320b in the regulation of the KITLG gene and consequently in the inflammatory process. This study confirmed that miR-320b can distinguish patients with COVID-19 from control participants; however, further research is needed to determine whether this miRNA can be used as a target or a biomarker.

Healthcare Workers (HCWs) and non-HCWs reaction to Bacillus Calmette-Guérin (BCG) in the BATTLE trial.

OBJECTIVES: Healthcare workers (HCWs) may have different response to Bacillus Calmette-Guérin (BCG) vaccination due to previous occupational exposure to Mycobacterium particles. We report subgroup analysis of the BATTLE trial, comparing BCG effects in HCWs vs non-HCWs. This was a secondary analysis of a trial. METHODS: The BATTLE trial was a double-blind placebo-controlled phase III clinical trial that investigated BCG revaccinating adults who were recently infected with SARS-CoV-2 virus. BCG and placebo recipients were sub-grouped based on regular occupational contact with patients into HCWs (48 BCG and 50 placebo) and non-HCWs (124 BCG and 134 placebo). Weekly COVID-19 symptom progression and injection site reactions were compared between subgroups on weeks one, two, three, and six follow-ups. RESULTS: HCWs were more likely to complain of itching on the injection site early after injection (OR = 2.5, p = 0.049). They developed peeling and crusting on the site of injection faster than non-HCWs (during the second week, p = 0.033 and 0.040, OR = 3.3 and 2.7, respectively). HCWs were also more likely to maintain their papule or develop a late onset pustule during later weeks (weeks four and six, p = 0.024 and 0.006, OR = 2.2 and 8.6, respectively). In terms of COVID-19 symptom progression, recovery from anosmia was more likely in the non-HCWs who received BCG (week six, pHolm's corrected = 0.002, OR = 3.3). CONCLUSION: HCWs' local reaction to BCG injection was slightly more rapid and more intense, possibly due to their occupational exposure. BCG may also ameliorate COVID-19 induced inflammation and anosmia in non-HCWs but not HCWs. Therefore, HCWs might be less likely to benefit from BCG vaccination. CLINICALTRIALS: gov register number NCT04369794.

Comparing Bacillus Calmette-Guérin (BCG) strains in convalescent COVID-19 patients.

Aim: We previously published results of the BATTLE trial, showing that patients recently infected with SARS-CoV-2 can benefit from receiving Bacillus Calmette-Guérin (BCG) with minimal adverse effects. The study incorporated two strains of this vaccine. In this study, patient outcomes were compared based on the strain of BCG because different strains have been shown to have different immunogenicity. Methods: BATTLE was a double-blind controlled trial of COVID-19 convalescent patients; symptom progression, injection-site lesion characteristics and adverse effects were compared between recipients of placebo, Russian BCG strain or Brazilian BCG strains. Results: There was no statistically significant difference between the two BCG strains in terms of symptom progression, lesion-size or type. Conclusion: The two strains have similar clinical outcomes in COVID-19 convalescent patients.

We previously published results of the BATTLE trial, showing that patients recently infected with SARS-CoV-2 virus can benefit from receiving BCG with minimal adverse effects. This article shows that the two BCG strains, Russian and Brazilian, have similar clinical outcomes in COVID-19 convalescent patients.

Time Analysis of an Emergent Infection Spread Among Healthcare Workers: Lessons Learned from Early Wave of SARS-CoV-2.

Aim: To find whether an emergent airborne infection is more likely to spread among healthcare workers (HCW) based on data of SARS-CoV-2 and whether the number of new cases of such airborne viral disease can be predicted using a method traditionally used in weather forecasting called Autoregressive Fractionally Integrated Moving Average (ARFIMA). Methods: We analyzed SARS-CoV-2 spread among HCWs based on outpatient nasopharyngeal swabs for real-time polymerase chain reaction (RT-PCR) tests and compared it to non-HCW in the first and the second wave of the pandemic. We also generated an ARFIMA model based on weekly case numbers from February 2020 to April 2021 and tested it on data from May to July 2021. Results: Our analysis of 8998 tests in the 15 months period showed a rapid rise in positive RT-PCR tests among HCWs during the first wave of pandemic. In the second wave, however, positive patients were more commonly non-HCWs. The ARFIMA model showed a long-memory pattern for SARS-CoV-2 (seven months) and predicted future new cases with an average error of ±1.9 cases per week. Conclusion: Our data indicate that the virus rapidly spread among HCWs during the first wave of the pandemic. Review of published literature showed that this was the case in multiple other areas as well. We therefore suggest strict policies early in the emergence of a new infection to protect HCWs and prevent spreading to the general public. The ARFIMA model can be a valuable forecasting tool to predict the number of new cases in advance and assist in efficient planning.

BCG vaccine safety in COVID-19 convalescent adults: BATTLE a randomized controlled trial.

INTRODUCTION: The safety of BCG revaccination is uncertain and there is no data on its use in patients with COVID-19. METHODS: COVID-19 convalescent adults confirmed by SARS-CoV-2 RT-PCR in South-America were 1:1 randomized in the first 14 days of symptoms to BCG intradermal vaccine or placebo and evaluated for adverse events on days 7, 14, 21, and beyond 40 days. CLINICAL TRIAL REGISTRATION: NCT04369794. RESULTS: 151 placebo and 148 BCG patients were included in the final analysis, with an average age of 40.7 years. No severe adverse event to BCG was reported. On day 7, 130 (87.8%) of the BCG recipients had local reaction, average size of 10.6 ± 6.4 mm, compared to only 2 (1.3%) placebos. Lesions gradually shrunk in size (mean 10.5 mm, 9.7 mm, and 6.8 mm at 14, 21, and beyond 40 days, respectively. The number of symptoms in any of the visits was not different between groups, and anosmia resolved earlier (25.7% vs. 37.1% at 7 days, OR = 1.70, 1.01-2.89, p = 0.035) in the BCG recipients. CONCLUSION: The BCG revaccination is safe in convalescent COVID-19 adults of a tuberculosis endemic region, regardless of tuberculin or IGRA test results. Local adverse events were similar though occurred earlier to that previously reported in children.

Factors associated with not adopting healthy behavior among hypertensive individuals: a population-based study in Brazil.

Adoption of a healthy lifestyle is strongly recommended for the control of hypertension, but professional advice alone does not ensure uptake of healthy behavior. Therefore, this study aimed to investigate the factors-associated with non-adoption of healthy behaviors among individuals with a medical diagnosis of hypertension. It was a cross-sectional study using data from the National Health Survey (PNS) carried out in Brazil in 2013, based on interviews with adults (≥18 years) (n = 60,202). The outcome variable was the non-adoption-two or fewer-of healthy behaviors (regular physical activity, recommended consumption of fruit and vegetables, no excessive alcohol consumption, no smoking, and very low/low salt intake [self-perceived]). A logistic regression model was used to verify the factors-associated with non-adoption of healthy behaviors. Approximately 64% of the study sample did not adopt healthy behaviors, i.e., they adopted two or fewer healthy habits. The most frequently mentioned healthy behaviors were not drinking excessively (91.5%), followed by not smoking (86%). Short time since disease diagnosis (OR = 1.20, 95% CI: 1.01-1.43), not using antihypertensive medication (OR = 1.38, 95% CI: 1.13-1.68), not making regular doctor visits (OR = 1.43, 95% CI: 1.23-1.65), and good self-rated health (OR = 1.16, 95% CI: 1.01-1.36) increased the chance of individuals not adopting healthy behaviors compared with their respective reference categories, independently of gender, age, schooling, and economic status. Counseling strategies should consider patient particularities, and health professionals need to be aware of issues that can interfere with the adoption of healthy behaviors of hypertensive patients.