A recent article published in Cell Reports Medicine demonstrated that Bacillus Calmette-Guerin (BCG) vaccinations might offer a platform for protection against emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and other pathogenic infections in type 1 diabetics.
During the past 17 years, randomized clinical studies and epidemiological investigations showed that the BCG vaccine against tuberculosis protected people from numerous infections, such as upper respiratory tract infections, malaria, leprosy, bacterial, and viral infections. Additionally, the BCG vaccine might safeguard humans from immunological disorders like multiple sclerosis and type 1 diabetes.
There is a demand for effective and safe platform vaccines to immunize against SARS-CoV-2 infection and other contagious pathogens. As the SARS-CoV-2 pandemic got underway, epidemiological studies started to find a link between neonatal BCG vaccination and lower coronavirus disease 2019 (COVID-19) mortality and morbidity, even in elderly adults decades following the standard newborn vaccinations on a nation-by-nation basis. On the contrary, several global groups with various neonatal exposures, BCG strains, and other communities did not exhibit these benefits.
Since adults or newborns have never received the BCG vaccine in the United States (US), a randomized study of BCG for potential COVID-19 protection provides a clear comparison in a vaccine-naive US adult population.
About the study
In the current placebo-controlled, double-blinded, randomized phase II/III research, the scientists assessed the efficacy and safety of the multi-dose BCG vaccinations for preventing COVID-19 and other infectious illnesses in a SARS-CoV-2-unvaccinated, high-risk-community-based group, over 15 months, from 1 January 2020 to April 2021.
The authors aimed to discover whether the BCG vaccine would provide a platform vaccine approach to safeguard against a wide range of infectious diseases, such as SARS-CoV-2 infection in the at-risk population.
Type 1 diabetic adults were considered the high-risk group in the study. The team recruited 144 participants and randomly assigned 48 to placebo and 96 to BCG arms. Further, no volunteers dropped out during the 15-month research.
The present parallel trial was derived from an ongoing randomized, double-blinded study of BCG for treating long-established adult type 1 diabetes. Therefore, all participants were fully immunized with three BCG or placebo vaccinations at the SARS-CoV-2 pandemic onset in the US on 1 January 2020.
The study results indicated that, contrary to antigen-specific COVID-19 vaccinations, no participants experienced any systemic side effects from BCG during the vaccination period. Localized skin reactions are a known side effect of the BCG vaccine and typically start between two and four weeks after vaccination. No excessive local responses were documented as adverse reactions. Notably, other SARS-CoV-2 vaccinations were not yet available during the timespan of the trial and had no impact on the research.
The BCG vaccine was 92% effective against SARS-CoV-2 infection, with a cumulative incidence of 1% of BCG-treated subjects and 12.5% of placebo-treated volunteers meeting the criteria for confirmed COVID-19 diagnosis based on symptoms and positive serologies. Besides, the team discovered no polymerase chain reaction (PCR)-positive symptomatic subjects in the BCG arm, i.e., 0%, compared to five symptomatic, PCR-positive participants in the placebo cohort, i.e., 10.4%.
If only the PCR data were regarded, these results demonstrated 100% efficacy for the BCG vaccine against SARS-CoV-2 infection at 0.99 posterior probability. In addition, there were no SARS-CoV-2-related deaths in either the placebo group or the BCG group.
The researchers noted that excluding the COVID-19 viral epitope II, practically all SARS-CoV-2 domains included in the heatmap comparisons exhibited a noticeably greater cumulation of antibody reactivity in the placebo cohort relative to the BCG arm. Besides, BCG vaccination decreased the duration and severity of all infectious illness symptoms versus the placebo group.
Moreover, the study data showed that all infectious illness symptoms of BCG recipients were similar to or less severe than those of their household members. On the other hand, relative to their household members, most placebo participants experienced a more severe illness. BCG recipients typically felt milder symptoms than placebo recipients or non-diabetic household controls.
In conclusion, the study illustrated that the BCG vaccine offers efficient protection against COVID-19 and comprehensive protection against other infectious diseases in type 1 diabetic adults in the US.
The study findings also depicted that the BCG vaccination was efficient, safe, cost-effective, and perhaps protective against the constantly evolving SARS-CoV-2 strain of the COVID-19 pandemic, given its extensive protection against other infections. The authors mentioned that although the efficacy of the BCG vaccine requires one to two years to manifest, the immunity might last decades.