Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also been shown to induce protection against various infections with a viral aetiology, leading to significant reductions in morbidity and mortality. We hypothesize that BCG vaccination might be a potent preventive measure against SARS-CoV-2 infection and/or may reduce disease severity in elderly people, who are known to be at increased risk of illness and death from SARS-CoV-2 infection. Therefore, we will in this placebo-controlled adaptive multi-centre randomized controlled trial evaluate the ability of BCG to reduce hospital admission and its efficacy to improve the clinical course of SARS-CoV-2 infection in elderly people((≥ 60 years of age).
On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2)
outbreak a pandemic. The number of confirmed cases continues to rise, leading to significant
morbidity and mortality worldwide. Although individuals of any age can acquire SARS-CoV-2,
adults of middle age and older are most commonly affected. Moreover, recent reports
demonstrate that mortality rates rise significantly among patients 60 years and older.
Therefore, strategies to prevent SARS-CoV-2 infection or to reduce its clinical consequences
in elderly are desperately needed. Bacillus Calmette-Guérin (BCG) vaccine not only protects
against tuberculosis, but has also been shown to induce protection against various infections
with a viral aetiology, leading to significant reductions in morbidity and mortality. We
hypothesize that BCG vaccination may reduce hospital admission and improve the clinical
course of symptoms of elderly people during the SARS-CoV-2 outbreak. Primary objective: To
reduce hospital admission of community dwelling older persons during the pandemic of
SARS-CoV-2. Secondary objective: To reduce disease severity, the duration of hospital
admission, ICU admission, or death in elderly during the pandemic of SARS-CoV-2.
Study design: A placebo-controlled adaptive multi-centre randomized controlled trial.
Study population: Elderly people (≥ 60 years of age). Intervention: Participants will be
randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio.
Biological: BCG vaccine
Bacille Calmette-Guérin is a live attenuated strain of Mycobacterium bovis developed in 1921 to prevent tuberculosis and other mycobacterial related infections.
Biological: Placebo
0.9% NaCl
Inclusion Criteria:
- Adult (≥ 60 years)
Exclusion Criteria:
- Fever (>38 ºC) within the past 24 hours
- Suspicion of current active viral or bacterial infection
- Expected vaccination during the first three months of the study period
- Severely immunocompromised subjects. This exclusion category comprises: a) subjects
with known infection by the human immunodeficiency virus (HIV-1); b) neutropenic
subjects with less than 500 neutrophils/mm3; c) subjects with solid organ
transplantation; d) subjects with bone marrow transplantation; e) subjects under
chemotherapy; f) subjects with primary immunodeficiency; g) severe lymphopenia with
less than 400 lymphocytes/mm3; h) treatment with any immunosuppressant drugs such as
anti-cytokine therapies, and treatment with oral or intravenous steroids defined as
daily doses of 10mg prednisone or equivalent for longer than 3 months, or probable use
of oral or intravenous steroids in the following four weeks.
- Active solid or non-solid malignancy or lymphoma within the prior two years
- Active participation in another research study that involves BCG administration
Radboud University
Nijmegen, Gelderland, Netherlands
UMC Utrecht
Utrecht, Netherlands