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.

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.

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.

Incontinence after laparoscopic radical prostatectomy: a reverse systematic review.

PURPOSE: To report the prevalence of the definitions used to identify post-prostatectomy incontinence (PPI) after laparoscopic radical prostatectomy (LRP), and to compare the rates of PPI over time under different criteria. MATERIALS AND METHODS: In the period from January 1, 2000, until December 31, 2017, we used a recently described methodology to perform evidence acquisition called reverse systematic review (RSR). The continence definition and rates were evaluated and compared at 1, 3, 6, 12, and >18 months post-operative. Moreover, the RSR showed the "natural history" of PPI after LRP. RESULTS: We identified 353 review articles in the systematized search, 137 studies about PPI were selected for data collection, and finally were included 203 reports (nr) with 51.436 patients. The most used criterion of continence was No pad (nr=121; 59.6%), the second one was Safety pad (nr=57; 28.1%). A statistically significant difference between continence criteria was identified only at >18 months (p=0.044). From 2013 until the end of our analysis, the Safety pad and Others became the most reported. CONCLUSION: RSR revealed the "natural history" of PPI after the LRP technique, and showed that through time the Safety pad concept was mainly used. However, paradoxically, we demonstrated that the two most utilized criteria, Safety pad and No pad, had similar PPI outcomes. Further effort should be made to standardize the PPI denomination to evaluate, compare and discuss the urinary post-operatory function.

Presence and predominance of histological grade 3 define cT1HG bladder cancer prognostic groups.

PURPOSE: Current World Health Organization/International Society of Urological Pathology (2004 WHO/ISUP) grading of bladder urothelial carcinoma relies on the highest pathologic grade of the specimen and does not reflect the inherent qualitative and quantitative heterogeneity of disease. MATERIALS AND METHODS: We retrospectively studied consecutive urothelial high-grade cT1 (cT1HG) carcinomas submitted to adjuvant bacille Calmette-Guérin between 2008 and 2015 to evaluate the prognostic potential of grade 3 (presence or predominance) according to the 1973 WHO system concerning disease progression and cancer-specific death. RESULTS: Among 253 patients, grading distribution was 34.4% 1+2, 7.5% 2+1, 20.2% 2+2, 19.0% 2+3, 5.1% 3+2, and 13.8% 3+3. Recurrence was diagnosed in 115 (45.5%), progression in 83 (32.8%), and cancer-specific death in 50 patients (19.8%). Mean time to recurrence, progression, and death from disease were 35.9±31.7, 47.6±44.5, and 51.2±50.4 months, respectively. Grade 3 presence (2+3, 3+2, or 3+3) occurred in 96 (37.9%) and independently predicted time to progression (p<0.001; hazard ratio [HR], 3.11; 95% confidence interval [CI], 1.88-5.14). Grade 3 predominance (3+2 or 3+3) occurred in 48 (18.9%) and independently predicted time to disease-specific death. CONCLUSIONS: Grade 3 presence and predominance are independent predictors of progression and disease-specific death and occur in about 40% and 20% of cT1HG, respectively. Describing qualitative and quantitative heterogeneity in urothelial carcinoma grading might improve the stratification of patients. This gives three prognostic high-grade groups based on WHO/ISUP 1973: prognostic grade group I (grade 3 absence), prognostic grade group II (grade 3 presence), and prognostic grade group III (grade 3 predominance).