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Background: Bacillus Calmette-Guérin (BCG) injected during the COVID-19 convalescence period was safe and enhanced recovery from anosmia and dysgeusia in the acute phase., Objectives: To report the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19., Methods: Design: Double-blind, placebo-controlled, randomized (1:1) clinical trial., Intervention: BCG intradermal vaccine and placebo., Patients: A total of 157 BCG and 142 placebo recipients participated in the 6-month follow-up, and 97 BCG and 95 placebo recipients participated in the 12-month follow-up., Measurements: Long COVID symptoms and mechanistic analyses., Results: BCG reduced hearing problems at 6 months (odds ratio [OR] = 0.26) and sleeping, concentration, memory, and vision problems at 12 months (OR = 0.45, 0.36, 0.38, and 0.36, respectively). Sensitivity analyses confirmed that long COVID-19 symptoms were reduced at the 6- and 12-month follow-ups (p = 0.010 and 0.031, respectively). BCG's crossover interaction paradoxically increased hair loss in women and decreased it in men at 6 months (p = 0.032). BCG immunomodulation is likely mediated through inhibition of Fas ligand expression in the blood and increased induction of IL6, IL10, interferon-induced transmembrane protein 3, and angiotensin-converting enzyme 2 in cultured human macrophages., Conclusion: Long-term follow-up of the BATTLE trial participants revealed that BCG protects against long COVID development if administered within the COVID-19 convalescence period. The response to BCG was subject-specific, including a paradoxical crossover interaction based on sex., Limitations: Not tested for previous mycobacterial exposure; loss to follow-up, particularly at 12 months., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

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., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2024 Yadollahvandmiandoab et al.)

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, p Holm'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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Leonardo O. Reis reports financial support was provided by State University of Campinas., (Copyright © 2023. Published by Elsevier Ltd.)

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., Competing Interests: The authors declare that they have no competing interests in this work., (© 2022 Leme et al.)

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., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Leonardo O. Reis reports financial support was provided by Coordination of Higher Education Personnel Improvement.]., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.

Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February and 11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average traveled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil and provides evidence that current interventions remain insufficient to keep virus transmission under control in this country., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)