Short summary

Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other infections; significant reductions in morbidity and mortality have been reported, and a plausible immunological mechanism has been identified: "Trained innate immunity". We hypothesize that BCG vaccination can reduce the risk of COVID-19 and other infections among senior citizens during the COVID-19 pandemic.

Rationale

Background: The virus SARS-CoV-2 has spread rapidly throughout the world. Seniors are at high risk of severe COVID-19 when infected. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other infections; significant reductions in morbidity and mortality have been reported, and a plausible immunological mechanism has been identified: "trained innate immunity".

We hypothesize that BCG vaccination can reduce the risk of COVID-19 and other infections among senior citizens during the COVID-19 pandemic.

Objectives:

rimary objective: To reduce senior citizens' risk of acute infection during the COVID-19 pandemic.

Secondary objectives: To reduce senior citizens' risk of SARS-CoV-2 infection during the COVID-19 pandemic. To reduce senior citizens' risk of self-reported respiratory illness during the COVID-19 pandemic.

Study design: A placebo-controlled randomized trial.

Study population: 1900 seniors above 65 years of age.

Intervention: Participants will be randomized 1:1 to intradermal administration of a standard dose of BCG vaccine or placebo (saline).

Outcomes:

Primary outcome: Acute infection identified either by a doctor, antibiotics use, hospitalization, or death due to infection.

Secondary outcomes: Verified SARS-CoV-2 infection and self-reported respiratory illness. With an expected incidence of acute infection of 20%, we will be able to show a 25% reduction in the risk of acute infection in the intervention group versus the placebo group by including a total of 1900 individuals, 950 individuals in each group.

Risk for participants and impact: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. If BCG can reduce the acute morbidity in seniors by 25% it has tremendous public health importance, both during the COVID-19 pandemic and overall.

Description of the cohort

Senior citizens of 65 years of age or older.

Data and biological material

Blood samples, data from questionnaires and register data.

Collaborating researchers and departments

OPEN Open Patient data Explorative Network, Odense University Hospital

• Professor, MD, DMSc Christine Stabell Benn
• DMSc Peter Aaby
• PhD Mette Bliddal
• MSc, Statistician Sebastian Nielsen
• MD, PhD Frederik Schaltz-Buchholtzer

Municipality of Odense

• MD, PhD Lene Annette Norberg

Radboud Medical Centre, Nijmegen, The Netherlands

• Professor, MD, DMSc Mihai Netea

Statens Serum Institut

• MD, PhD Tyra Grove Krause

Department of Clinical Immunology, Odense University Hospital

• Professor, MD, DMSc Torben Barington