A retrospective, observational study has found that people who received the BCG vaccination — which prevents tuberculosis — were less likely to report symptoms of COVID-19 and less likely to have antibodies against the infection in their blood.

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Scientists developed the BCG (bacillus Calmette-Guérin) vaccine more than 100 years ago to protect against the bacterial infection tuberculosis (TB).

According to the World Health Organization (WHO), by 2004, around 100 million children a year were receiving the vaccine.

In the United States, BCG is approved for people at high risk of developing TB and for treating some forms of bladder cancer.

But research also suggests that BCG vaccination early in life can reduce child mortality by up to 45%, mainly through reduced susceptibility to sepsis (blood poisoning) in babies, respiratory infections, and fever.

In adolescents and older people, there is also some evidence that BCG protects against viral respiratory infections.

Scientists believe the vaccine primes the “innate” immune system, the body’s first line of defense against viruses and other invading organisms. Unlike adaptive immunity, innate immunity rarely targets specific pathogens that the body has encountered in the past.

Researchers at the Cedars-Sinai Medical Center in Los Angeles, CA, wondered whether BCG might reduce susceptibility to SARS-CoV-2, the virus that causes COVID-19.

“We were interested in studying the BCG vaccine because it has long been known to have a general protective effect against a range of bacterial and viral diseases other than TB, including neonatal sepsis and respiratory infections,” says co-senior author Dr. Moshe Arditi, director of the Pediatric and Infectious Diseases and Immunology Division at Cedars-Sinai.

The team has reported their results online in The Journal of Clinical Investigation.

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Between May 11 and June 18, 2020, 6,201 healthcare workers gave blood samples and answered questions about their medical history, including whether they had received BCG and vaccines against two other bacterial infections and influenza.

In total, 1,836 said they had received the BCG vaccination, 4,275 said they had not received it, and 90 were unsure.

Those with the vaccination were less likely to report experiencing symptoms of COVID-19 at any time in the past 6 months.

Overall, 3.5% of the entire cohort tested positive for SARS-CoV-2 antibodies.

Among those who reported receiving the BCG vaccine, 2.7% tested positive, while among those who said they hadn’t received it, 3.8% tested positive.

“It appears that BCG-vaccinated individuals either may have been less sick and therefore produced fewer anti-SARS-CoV-2 antibodies, or they may have mounted a more efficient cellular immune response against the virus,” says Dr. Arditi.

After adjusting for age and sex, BCG vaccination — but none of the other vaccinations — was still associated with a reduced likelihood of testing positive for SARS-CoV-2 antibodies.

In their paper, the researchers write:

“Taken together, these results indicate that a history of BCG vaccination confers a nonspecific protective effect against infection with SARS-CoV-2 and decreases the presence of self-reported COVID-19 symptoms. This appears to be specific to BCG, as [other vaccinations] […] are not associated with similar protection against infection with SARS-CoV-2.”

One of the study’s limitations was that it relied on participants’ recollection of which vaccines they had received, and whether they had experienced typical COVID-19 symptoms in the previous 6 months.

In addition, the numbers in each group who developed symptoms or tested positive were relatively small, which limited the statistical power of the study and the reliability of its findings.

However, it is interesting to note that those who reported receiving the BCG vaccination were older on average. They were also more likely to have diabetes, hypertension, cardiovascular disease, and chronic obstructive pulmonary disease.

These are all factors that increase a person’s chances of developing a severe COVID-19 infection.

In August 2020, Medical News Today reported another observational study, which suggested countries with mandatory BCG vaccination had a degree of “herd immunity” against the disease.

There are 22 clinical trials currently investigating BCG’s potential to prevent or treat COVID-19, which should provide more definitive evidence. Dr. Arditi and Cedars-Sinai are involved in one of the studies.

No-one believes BCG will be more effective than specific vaccines for COVID-19, Dr. Arditi explains. But if the trials prove its worth, as a well-established vaccine, BCG could be quickly approved and rolled out for this application.

“It is a potentially important bridge that could offer some benefit until we have the most effective and safe COVID-19 vaccines made widely available,” he says.

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