Using BCG Vaccine to Enhance Nonspecific Protection of Health Care Workers During the COVID-19 Pandemic: A Randomized Controlled Trial.

BACKGROUND: The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes. RESULTS: There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98-1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07-5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI, .09-.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI, .96-1.24). CONCLUSIONS: In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes. CLINICAL TRIALS REGISTRATION: NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90).

Using BCG vaccine to enhance non-specific protection of health care workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark.

OBJECTIVES: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism.The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. HYPOTHESIS: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. TRIAL DESIGN: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. PARTICIPANTS: The trial will recruit 1,500 HCW at Danish hospitals.To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week.A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. MAIN OUTCOMES: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation.Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation.Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1.Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference.The physicians administering the treatment are not blinded.Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group.Trial Status: Current protocol version 5.1, from July 6, 2020.Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. TRIAL REGISTRATION: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291.Full protocol: The full protocol is attached as an additional file, accessible from the Trialswebsite (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Infections after transrectal ultrasonic guided prostate biopsies - a retrospective study.

Background: Transrectal ultrasound guided biopsies (TRUSp) are associated with a risk of serious infections. Recently, there has been a rise in incidence of infections after TRUSp and quinolone-resistant bacteria. The most commonly used prophylaxis is ciprofloxacin (CFLX). Objective: To document the incidence and risk factors of post-TRUSp infections and investigate the microbial resistance patterns for the patients presenting with a serious infection after TRUSp. Materials and methods: Data were collected, including age, comorbidity, previous TRUSp, number of biopsies, previously received antibiotics, time between TRUSp and hospitalization, results of microbiological cultivations, antibiotic prophylaxis, and development of infection for all patients at The University Hospital of Southern Denmark, Esbjerg who underwent TRUSp from November 2014 to November 2016. Results: In total, 590 patients were included and 37 (6.1%) patients were hospitalized with symptoms of infection. Of those 37 patients, 21 (56,8%) patients had positive microbiology (blood and/or urine), 18 (48.6%) patients were infected with E. coli and 11 (29.7%) patients had CFLX-resistant E. coli. If patients had previously received antibiotics, they had a significantly higher risk of developing infection after TRUSp (p = 0.01). Conclusion: Patients who have been exposed to antibiotics before TRUSp are at higher risk of developing serious infections as a complication to TRUSp. CFLX-resistant E. coli were a major reason for hospitalization.