Last updated on February 7th, 2023 at 01:35 pm
A new study shows that the BCG vaccine (for tuberculosis) is ineffective against COVID-19. You may be wondering why anyone would use it for COVID-19. Still, the BCG vaccine has some exciting characteristics that led to the hypothesis that the vaccine might prevent or improve the outcomes of COVID-19.
I wrote previously about new clinical studies involving the BCG vaccine; however, it’s not surprising that it didn’t work against COVID-19. Nevertheless, the vaccine has numerous applications outside of preventing tuberculosis and not working for COVID-19 which makes it one of the more exciting vaccines out there.
We will take a look at the BCG vaccine and the new study that shows it does not work for COVID-19.
All about the BCG vaccine
Before we jump into this, we should talk about the vaccine itself.
The Bacillus Calmette-Guerin vaccine, or BCG vaccine, was initially developed to prevent tuberculosis. That disease is caused by a bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. Tuberculosis is treatable with advanced medicines, but it takes a long time and can be expensive. Without treatment, the patient will die.
The BCG vaccine is one of the oldest vaccines available on the market, first used in 1921 (pdf). With the successful eradication of tuberculosis in many countries, the vaccine is rarely used in those countries. However, it is still given to about 100 million children every year in countries where tuberculosis is still endemic.
The BCG vaccine works like most vaccines – it is made from an attenuated, live bovine tuberculosis bacillus, Mycobacterium bovis which induces an adaptive immune response against tuberculosis bacterium.
At this point, you’re wondering why this vaccine is still around or important. Well, it seems it has some other purposes.
- There is some very preliminary, but promising, research that the BCG vaccine may help reverse type 1 diabetes. We’re a long way from knowing if it will work, but it is encouraging researchers looking for a “cure” for type 1 diabetes.
- The BCG vaccine is one of the most successful immunotherapies for some forms of cancer. In fact, the vaccine is the “standard of care with bladder cancer,” specifically for non-muscle-invasive bladder cancer (NIMBC), since about 1977. The vaccine seems to treat and prevent the recurrence of NIMBC. Unfortunately, low supplies of the BCG vaccine have caused a shortage of the BCG vaccine for cancer patients. Just to be clear, the BCG vaccine is not a vaccine against bladder cancer, it is part of the immunotherapy for the disease – the vaccine is injected directly into the bladder.
- The vaccine has also been evaluated as a therapy for colorectal cancer. It is being evaluated as an adjuvant to autologous colorectal cancer cells for the treatment of stage II colon cancer. Moreover, a number of other cancer vaccines undergoing development use the BCG vaccine as an adjuvant to provide an initial stimulation of the patient’s immune system.
- In a secondary analysis of a BCG vaccination trial, conducted between 1935-1938 (yes, 1935-38), of 2,963 American Indian/Alaskan Native children aged <20 in five states, researchers found BCG vaccine group had a significantly lower rate of lung cancer, after adjusting for a variety of confounders including tobacco smoking history, alcohol abuse, and sex of participants. The BCG vaccine group had approximately 18.2 cases per 100,000 person-years compared to 45.4 cases for the placebo group. That is a 2.5X reduction in the risk of lung cancer. However, there are a lot of concerns about this study, and I don’t think that we’re close to the vaccine becoming a standard of care for preventing lung cancer.
- There is some preliminary evidence that the BCG vaccine may reduce the incidence of Alzheimer’s disease. The researchers showed that, among bladder cancer patients, patients who did not receive the BCG vaccine therapy had a 4.7X higher risk of Alzheimer’s disease compared to those who did. This is an interesting study that might become a future research direction.
Scientists aren’t sure why the vaccine is effective against some cancers (and please don’t assume that it works as a treatment for hundreds of different cancers). It is possible that the BCG vaccine stimulates the immune system in such a way that it causes it to attack bladder cancer. But more research is necessary to determine the mechanisms, which could help improve it for cancer therapy.
Ironically, the vaccine has a very wide range of effectiveness, and we probably should develop a better vaccine. Since it’s mostly used for children in underdeveloped countries, there probably isn’t much incentive to improve it. That’s sad.
BCG vaccine and COVID-19 study
In a study published on 31 January 2023 in Clinical Microbiology and Infection, Eva L. Koekenbier, MD, and colleagues examined the results of a 6000-patient phase 3 clinical trial comparing the BCG vaccine to a placebo group.
These are the key results:
- In a group of older patients with a median of two comorbidities, COVID infections were reported in 4.2% of patients who received the BCG vaccine compared with 3.7% of those given a placebo, hazard ratio (HR) = 1.12. In other words, the BCG vaccine showed a statistically insignificant increase in the risk of COVID-19 infection.
- Clinically relevant respiratory tract infections were reported by 66 patients in the BCG vaccine group and 72 in the placebo group, HR = 0.92.
- COVID-related hospitalizations occurred in 18 BCG recipients and 21 placebo recipients, HR = 0.86.
- Thirteen BCG recipients died compared with 18 placebo recipients, HR = 0.71.
- There were five deaths in the BCG group and six in the placebo group related to COVID.
These results compare favorably to two recent randomized placebo-controlled trials that showed that the BCG vaccine was not effective against COVID in healthcare workers and relatively healthy adults.
Although the BCG vaccine has some promise in treating cancer (it already is useful in some forms of bladder cancer) and type 1 diabetes, it is not very useful in preventing COVID-19 infections. These COVID-19 studies were started early in the pandemic when we didn’t have viable vaccines, and the BCG vaccine seems to have shown some promise in animal studies.
Now, we have data that it doesn’t work for stopping COVID-19. However, research on its usefulness in other diseases continues. Stay tuned.
- BCG vaccines: WHO position paper – February 2018. Vaccins BCG: Note de synthèse de l’OMS – Février 2018. Wkly Epidemiol Rec. 2018;93(8):73–96. Published 2018 Feb 23.
- Escobar LE, Molina-Cruz A, Barillas-Mury C. BCG vaccine protection from severe coronavirus disease 2019 (COVID-19). Proc Natl Acad Sci U S A. 2020 Jul 9:202008410. doi: 10.1073/pnas.2008410117. Epub ahead of print. PMID: 32647056.
- Gofrit ON, Klein BY, Cohen IR, Ben-Hur T, Greenblatt CL, Bercovier H. Bacillus Calmette-Guérin (BCG) therapy lowers the incidence of Alzheimer’s disease in bladder cancer patients. PLoS One. 2019;14(11):e0224433. doi: 10.1371/journal.pone.0224433. eCollection 2019. PubMed PMID: 31697701; PubMed Central PMCID: PMC6837488.
- Moorlag SJCFM, Taks E, Ten Doesschate T, van der Vaart TW, Janssen AB, Müller L, Ostermann P, Dijkstra H, Lemmers H, Simonetti E, Mazur M, Schaal H, Ter Heine R, van de Veerdonk FL, Bleeker-Rovers CP, van Crevel R, Ten Oever J, de Jonge MI, Bonten MJ, van Werkhoven CH, Netea MG. Efficacy of BCG Vaccination Against Respiratory Tract Infections in Older Adults During the Coronavirus Disease 2019 Pandemic. Clin Infect Dis. 2022 Aug 24;75(1):e938-e946. doi: 10.1093/cid/ciac182. PMID: 35247264; PMCID: PMC8903481.
- Ten Doesschate T, van der Vaart TW, Debisarun PA, Taks E, Moorlag SJCFM, Paternotte N, Boersma WG, Kuiper VP, Roukens AHE, Rijnders BJA, Voss A, Veerman KM, Kerckhoffs APM, Oever JT, van Crevel R, van Nieuwkoop C, Lalmohamed A, van de Wijgert JHHM, Netea MG, Bonten MJM, van Werkhoven CH. Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial. Clin Microbiol Infect. 2022 Sep;28(9):1278-1285. doi: 10.1016/j.cmi.2022.04.009. Epub 2022 Apr 28. PMID: 35489606; PMCID: PMC9046133.
- The writing committee for the BCG-PRIME study group; Writing committee; Koekenbier EL, Fohse K, van de Maat JS, Oosterheert JJ, van Nieuwkoop C, Hoogerwerf JJ, Grobusch MP, van den Bosch MAAJ, van de Wijgert JHH, Netea MG, Rosendaal FR, Bonten MJM, Werkhoven CHHV; BCG-PRIME study group. Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial. Clin Microbiol Infect. 2023 Jan 31:S1198-743X(23)00044-7. doi: 10.1016/j.cmi.2023.01.019. Epub ahead of print. PMID: 36736662; PMCID: PMC9892323.