Short summary

In this cohort study we will link data from the Copenhagen School Health Record Register (CSHRR) to data Danish register data on confirmed COVID-19 cases and hospitalisations.

We will use the data to examine the hypothesis that BCG vaccination during childhood decreases the risk of confirmed COVID-19 cases by 20% by comparing birth cohorts between 1968-1974, during the time when BCG was phased out.

Rationale

Background

The Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis has been shown in numerous studies to have beneficial non-specific effects on overall health and survival (1-3). These findings are supported by immunological studies showing a biological mechanism whereby BCG may be able to train the innate immune system (4).

Long-term effects of BCG vaccination on survival until early adult life (follow-up to 2010) have been indicated using data from the Copenhagen School Health Record Register (CSHRR) (5).

Currently trials are undertaken to test the immediate effect of providing BCG to adults to protect them against COVID-19 (6). It has also been shown that countries with a BCG childhood vaccination program have lower COVID-19 mortality (7), but these findings are based on ecological analyses and prone to bias. Cohort studies with long term follow-up of comparable groups of individuals exposed or not exposed to BCG are warranted.

We aim to conduct a follow-up of the CSHRR cohort born from January 1968 to June 1974, which experienced the phase out of BCG in Denmark, in order to investigate whether BCG vaccination in childhood may carry a long-term protective effect on COVID-19 infection and COVID-19 hospital admission.

Furthermore, we will conduct a new analysis of the long-term effect of BCG vaccination on survival (4), where data has been updated to 2020.

Hypotheses

Primary hypothesis

BCG vaccination registered at school entry (~7 years old) reduces the risk of COVID-19 infection and COVID-19 hospital admission by 20%.

Secondary hypotheses Smallpox vaccination registered at school entry (~7 years old) reduces the risk of COVID-19 infection and COVID-19 hospital admission by 20%. BCG vaccination registered at school entry (~7 years old) reduces all-cause mortality by 40% between the registered school entry and 2020.

Description of the cohort

We plan a cohort study that will include all data from the CSHRR cohort born from January 1968 to June 1974. Information on childhood vaccinations, social characteristics and anthropometric measurements was recently digitalized in this part of the cohort which is important for the current study. Using the Danish unique ID numbers, we will link these individuals to the data on confirmed COVID-19 cases.

When sufficient confirmed COVID-19 cases have been registered, we will perform an interim analysis. This will later be followed by a full analysis when the COVID-19 pandemic has ended.

Data and biological material

We will use information about childhood vaccination, background characteristics and health and social information in childhood from the Copenhagen School Health Record Register. This cohort will be merged with information about positive COVID-19 testing, hospitalisation with COVID-19 and information about country of origin of the child and the parents.

Further we will consider including information on co-morbidity, use of medicine, address at the beginning of the pandemic to be able to adjust for potential regional differences and confounding in the data.

Collaborating researchers and departments

Department of Clinical Research, University of Southern Denmark

• Christine Stabell Benn
• Peter Aaby

Department of Biostatitics, University of Copenhagen

• Thorkild I.A. Sørensen
• Andreas Rieckmann

Department of Economics, Copenhagen Business School

• Moira Daly
• Cédric Schneider

Department of Clinical Epidemiology, University of Aarhus

• Signe Sørup

Publications associated with the project

5. Andreas Rieckmann et al., Vaccinations against smallpox and tuberculosis are associated with better long-term survival: a Danish case-cohort study 1971-2010, International Journal of Epidemiology, Volume 46, Issue 2, April 2017, Pages 695-705.