Efficacy of BCG Vaccination in the Prevention of COVID19 Via the Strengthening of Innate Immunity in Health Care Workers — COVID-BCG  

Infection Clinical Trial

Official title: Randomized Controlled Trial Evaluating the Efficacy of Vaccination With Bacillus Calmette and Guérin (BCG) in the Prevention of COVID-19 Via the Strengthening of Innate Immunity in Health Care Workers

Status Recruiting

Clinical Trial Summary

Healthcare Workers (HCW) are at high risk for COVID-19. In addition to the risk of serious forms among HCW, significant absenteeism due to illness would have dramatic consequences in our ability to fight COVID-19. No coronavirus vaccine is available today and drug treatments are only at the start of clinical evaluation. Available since 1921, the bacillus Calmette and Guérin (BCG) is the most widely used vaccine in the world (> 3 billion doses administered) with an extremely low rate of adverse effects. BCG is indicated for the prevention of tuberculosis (TB), but more recent studies have shown that it also has nonspecific immune properties which may be interesting in the current COVID-19 epidemic. Data in mice and in humans have demonstrated protection conferred by BCG against viral respiratory infections such as influenza. In countries with high endemic TB, BCG decreases the incidence of acute respiratory infections by up to 80%, neonatal BCG vaccination has been shown to greatly reduce the risk of sepsis and of hospitalization of children for reasons other than TB. A recent study conducted in South Africa showed that re-vaccination with BCG in adults reduced the incidence of respiratory infections by 70% compared to unvaccinated controls. Beyond respiratory infections, BCG has also shown protective effects against inflammatory diseases. These non-specific beneficial effects are likely linked to the induction of "trained innate immunity", implying epigenetic and metabolic re-programming of innate immune cells. It is therefore possible that revaccination with BCG could significantly reduce the incidence and severity of COVID-19. Very recent ecological observations indeed suggest an inverse correlation between BCG vaccination coverage and the morbidity and mortality of COVID-19. In this context several trials began in Europe and Australia to evaluate the efficacy of BCG vaccination in populations at risk of exposure (HCW) or severe disease (elderly). This study is aligned with studies carried out in Australia, The Netherlands and Spain. In contrast to these latter studies, virtually all French study participants have been vaccinated in their childhood, since BCG vaccination was mandatory in France in neonates until 2007, and in HCW until recently. Therefore, the French study will be in a unique situation to evaluate the effect of re-vaccination with BCG in the context of BCG priming decades before revaccination.

Clinical Trial Description

Randomized, multicenter phase III controlled trial, in 2 parallel arms:

• One group vaccinated with BCG

• One group receiving placebo (0.9 % saline) Randomization in a 1: 1 ratio will be stratified on the center. The study will be proposed to all heath care workers eligible. At screening, the investigator will propose the study to the participant and explain the details by providing an information letter. After signature of the consent, evaluations specific for the study will be undertaken, such as clinical examination, blood sampling, nasopharyngeal sampling in case of clinical signs.

At the inclusion visit, participants corresponding to the inclusion criteria will be randomized to receive BCG or placebo.

Participants will receive a single dose of BCG vaccine (or placebo). The adult dose of BCG vaccine (or placebo) is 0.1 mL injected intradermally over the distal insertion of the deltoid muscle onto the humerus (approximately one third down the upper arm).

Follow-up visits will be done respectively at M3 and M6 and phone contacts between these two visits.

Blood samples will be collected prior to randomization (V0) and at 3 and 6 months to determine exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Where required, swab/blood samples will be taken at illness episodes to assess SARS-CoV-2 infection.

Participants will be followed for 6 months with regular mobile phone text messages 2 times weekly to collect local and general reactions until 30 days after vaccination and during the study to identify and detail COVID-19 infection.

Immunological studies will be conducted at a central Laboratory. Analysis will take place after M6 visits.

A nested study will be carried out on blood samples of 72 study subjects in order to evaluate the impact of COVID-19 on innate immunity. These blood samples will be collected at M6 among 6 groups, each containing 12 study subjects:

• One group of subjects vaccinated with BCG that have remained sero-negative for SARS CoV2

• One group of subjects having received placebo that have remained sero-negative for SARS CoV2

• One group of symptomatic subjects vaccinated with BCG

• One group of symptomatic subjects having received placebo.

• One group without symptoms but sero-positive for SARS CoV2 vaccinated with BCG

• One group without symptoms but sero-positive for SARS CoV2 vaccinated with placebo ;

Related Conditions & MeSH terms

• Infection
• Viral, Agent as Cause of Disease Classified Elsewhere

• NCT number: NCT04384549
• Study type: Interventional
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Odile LAUNAY, Professor
• Phone: 01 58 41 28 58
• Email: odile.launay@aphp.fr
• Status: Recruiting
• Phase: Phase 3
• Start date: May 20, 2020
• Completion date: February 20, 2021