BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial)

Pittet, Laure F; Messina, Nicole L.; Gardiner, Kaya; Orsini, Francesca; Abruzzo, Veronica; Bannister, Samantha; Bonten, Marc J. M.; Campbell, John; Croda, Júlio; Dalcolmo, Margareth; Elia, Sonja; Germano, Susie; Goodall, Casey; Gwee, Amanda; Jamieson, Tenaya; Jardim, Bruno; Kollmann, Tobias R.; Lacerda, Marcus Vinícius Guimarães; Lee, Katherine J.; Legge, Donna; Lucas, Michaela; Lynn, David J.; McDonald, Ellie; Manning, Laurens; Munns, Craig F; Perrett, Kirsten P.; Prat‐Aymerich, Cristina; Richmond, Peter; Shann, Frank; Sudbury, Eva; Villanueva, Paola; Wood, Nicholas; Lieschke, Katherine; Subbarao, Kanta; Davidson, Andrew; Curtis, Nigel

doi:10.1136/bmjopen-2021-052101

Cited by 35 publications

(39 citation statements)

References 37 publications

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“…Therefore, due to the supporting evidence obtained in experimental studies and according to the results presented in Table 3, this case report emphasizes that the BCG vaccine generates a protective effect against viral pathogens such as COVID-19 (Pittet et al, 2021).…”

Section: Discussionsupporting

confidence: 68%

“…Given the above, this case report makes clear the importance of BGG vaccination as a booster to the immune system of the general population, especially for the vulnerable of population in patients (Pittet et al, 2021).…”

Section: Discussionmentioning

confidence: 78%

“…Tuberculosis and COVID-19 linked to social distancing is largely to blame for the decrease in access to Tuberculosis healthcare and treatment (Pittet et al, 2021). This case report demonstrated that the absence of BCG vaccination is related to an increase in mortality in 60% of patients with a positive result for COVID-19 (Miller et al, 2020).…”

Section: Discussionmentioning

confidence: 80%

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COVID-19 in Socially Vulnerable Patients with Tuberculosis in Brazil

Ramos¹,

Araújo²,

Venturini³

et al. 2022

GJHS

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INTRODUCTION: COVID-19 is a global public health problem. The first case reported in the socially vulnerable population in the territory of Mato Grosso do State/Brazil occurred in August 2020. However, information about the co-infection of Tuberculosis (TB) and COVID-19 is rarely described in the world literature. Objective: to describe for the first time a group of vulnerable patients who died or not due to Tuberculosis and COVID-19, using a Cohort study of a control group and a treatment group. METHODS: Reporting 7 cases of TB associated with COVID-19 confirmed by respiratory RT-PCR, hospitalized in a hospital department of COVID-19 (CEAA: 42969320.0.0000.0021). RESULTS: The patients included in this case report were aged between 19 and 83 years, respectively, with a predominance of females, 4 patients were vaccinated with BCG. In addition, 3 patients died from COVID-19, and 2 patients were considered cured by COVID-19. The mean time to diagnosis between Tuberculosis and COVID-19 in the “control group” was 43 days and the mean time to diagnosis in the “treatment group” was 37 days. The average number of days of hospital stay in the “control group” was 50 days and in the “treatment group” it was 40 days. In the patients in the “control group”, 2 presented a unilateral pulmonary cavity lesion on the X-ray. In the “treatment group”, only 1 patient presented a unilateral pulmonary cavity lesion on the X-ray, and 2 presented a bilateral pulmonary cavity lesion, and only one developed bilateral non-cavitary lesion with infiltrates. Regarding drug resistance to the treatment of Tuberculosis, in the “treatment group” only 2 patients were sensitive and 3 were resistant. On the other hand, in the “control group”, 1 patient presented resistance and 1 sensitivity. It was found that 4 patients with drug resistance to Tuberculosis died (57%). Among the patients who died, it was observed that patients aged 83, 70 years and 66 years were not vaccinated with Bacillus Calmette-Guérin (BCG). It was found in this case report that patients with COVID-19 and Tuberculosis have 60% less chance of cure. Furthermore, patients cured with pulmonary sequelae of COVID-19 may be at greater risk of developing advances in the worsening of Tuberculosis in the future. However, according to the results found in this case report, in some socially vulnerable regions where the forms of advanced Tuberculosis occur there is the presence of drug-resistant Mycobacterium Tuberculosis strains. CONCLUSION: Our study showed that Mycobactrium tuberculosis (MTB) infection in the socially vulnerable population increased the susceptibility to SARS-CoV-2 and the severity of COVID-19 or vice-versa. Based on this case report, it is recommended that, in the socially vulnerable population, the status of MTB infection be verified in patients with suspected COVID-19 at hospital admission.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 80%

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COVID-19 in Socially Vulnerable Patients with Tuberculosis in Brazil

Ramos¹,

Araújo²,

Venturini³

et al. 2022

GJHS

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show abstract

“…In the low TB endemic setting of this study, a local adverse reaction was not attributable to LTBI. Our study has important implications for BCG vaccination policy in an era when BCG vaccination and revaccination is increasingly being considered for novel applications, including to reduce the impact of COVID-19 32 .…”

Section: Discussionmentioning

confidence: 95%

“…Healthcare workers (HCW) were recruited in Stage 1 of the BRACE trial in six hospitals in Australia from March to May 2020, and randomised in a 1:1 ratio and open-label design to receive BCG vaccine or no BCG 32 . All participants received influenza vaccine to the contralateral arm within three days.…”

Section: Methodsmentioning

confidence: 99%

Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

et al. 2022

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The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.

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Off‐target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2: implications for protection against severe COVID‐19

et al. 2022

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Background and objectives Because of its beneficial off‐target effects against non‐mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID‐19). Using samples from participants in a placebo‐controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID‐19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS‐CoV‐2. Methods This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID‐19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ‐irradiated SARS‐CoV‐2‐infected or mock‐infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single‐cell immunophenotyping was made by flow cytometry. Results BCG vaccination, but not placebo vaccination, reduced SARS‐CoV‐2‐induced secretion of cytokines known to be associated with severe COVID‐19, including IL‐6, TNF‐α and IL‐10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4+ and CD8+ T cells, and an activation of eosinophils in response to SARS‐CoV‐2. Conclusions The immunomodulatory signature of BCG’s off‐target effects on SARS‐CoV‐2 is consistent with a protective immune response against severe COVID‐19.

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BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial)

Cited by 35 publications

References 37 publications

COVID-19 in Socially Vulnerable Patients with Tuberculosis in Brazil

COVID-19 in Socially Vulnerable Patients with Tuberculosis in Brazil

Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

Off‐target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS‐CoV‐2: implications for protection against severe COVID‐19

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