Bacillus Calmette-Guérin vaccination as defense against SARS-CoV-2 (BADAS): a randomized controlled trial to protect healthcare workers in the USA by enhanced trained immune responses
Author:
DiNardo Andrew R., Arditi Moshe, Kamat Ashish M., Koster Kent J., Carrero Santiago, Nishiguchi Tomoki, Lebedev Maxim, Benjamin Aaron B., Avalos Pablo, Lozano Marisa, Moule Madeleine G., McCune Brittany, Herron Baysia, Ladki Malik, Sheikh Daanish, Spears Matthew, Herrejon Ivan A., Dodge Courtney, Kumar Sathish, Hutchison Robert W., Ofili Theresa U., Opperman Lynne A., Bernard Jessica A., Lerner Seth P., Udeani George, Neal Gabriel, Netea Mihai G., Cirillo Jeffrey D.ORCID
Abstract
Abstract
Background
A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.
Methods
This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at high risk, including those with comorbidities (hypertension, diabetes, obesity, reactive airway disease, smokers), racial and ethnic minorities, elderly, teachers, police, restaurant wait-staff, delivery personnel, health care workers who are defined as personnel working in a healthcare setting, at a hospital, medical center or clinic (veterinary, dental, ophthalmology), and first responders (paramedics, firefighters, or law enforcement), will be randomly assigned to two treatment groups. The treatment groups will receive intradermal administration of BCG vaccine or placebo (saline) with groups at a 1:1 ratio. Individuals will be tracked for evidence of SARS-CoV-2 infection and severity as well as obtaining whole blood to track immunological markers, and a sub-study will include cognitive function and brain imaging. The majority of individuals will be followed for 6 months, with an option to extend for another 6 months, and the cognitive sub-study duration is 2 years. We will plot Kaplan-Meier curves that will be plotted comparing groups and hazard ratios and p-values reported using Cox proportional hazard models.
Discussion
It is expected this trial will allow evaluation of the effects of BCG vaccination at a population level in high-risk healthcare individuals through a mitigated clinical course of SARS-CoV-2 infection and inform policy making during the ongoing epidemic.
Trial registration
ClinicalTrials.gov NCT04348370. Registered on April 16, 2020.
Funder
Texas A and M University
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Medicine (miscellaneous)
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