Rethinking BCG in the pandemic

Publicação: 8 de October de 2020

BCG has been studied in several situations linked to cellular immunity

In the pandemic, it has revealed itself as a vaccine that can teach the human immune system to prevent or ameliorate Sars-CoV-2 infection.

The number of deaths from COVID-19 in Brazil could be 14 times higher if the vaccine against the Bacillus Calmette-Guérin (BCG), which causes tuberculosis, was not mandatory in the country. The conclusion is from a study by the University of Michigan (USA) published in August in the journal Science. The paper revealed that lower rates of infection and death are repeated in all countries where vaccination is recommended. The daily rate of infections in 135 countries and deaths in 134 over the first 30 days of the pandemic in each nation were analyzed. Among the countries that have the recommended BCG are China, Brazil and France. Some nations recommended it because tuberculosis is no longer a threat, like Australia and Spain. Others never recommended it, like the USA and Italy.

In the midst of many uncertainties about the cure of COVID-19, Brazilian researchers are evaluating the effectiveness of this vaccine, old known in our National Vaccination Calendar, against the disease. Professor of Pulmonology and phthisiology at the Federal University of Rio de Janeiro (UFRJ) Dra. Fernanda Mello, coordinator of a clinical trial on BCG, explains that the ProBCG Rio study is a phase IIB clinical trial, that is, performed in a limited number of participants, with the aim of evaluating the vaccine’s effectiveness in situations of natural exposure infection, that is, in areas where there is active transmission of the infectious agent. “In view of the fact that health professionals are the portion of the population most at risk of contamination, they will be the participants of this study, where they will be submitted to vaccination with BCG or with placebo, and followed up in order to compare the groups regarding the occurrence of COVID-19 and / or its severe forms”, she details.

The study is expected to recruit participants in two to four months and to accompany them for one year. According to Dr. Mello, in approximately one and a half years all results should be available. She also points out that throughout the study partial analyses will be made, which may indicate the possible effects of BCG vaccination. However, there is no prediction of release of this vaccine to prevent COVID 19 and there is currently no available literature on its effect on animals infected with SARS-CoV-2.

Asked if the vaccine can protect against COVID-19, Dr. Mello recalls that it is formally indicated in newborns for the prevention of severe forms of tuberculosis. “However, several studies prove that it induces cross-protection for other infectious agents, including viral agents. Therefore, BCG could assist in the immune response to SARS-CoV-2” she points out. However, she explains that the vaccine is not specific to COVID-19, and may prove useful as long as a specific vaccine is not available on a large scale.

Regarding the immune mechanism, it seems to stimulate the induction of nonspecific innate immune response, whose epigenetic changes would influence the human reaction to other infectious agents. The BCG vaccine, by stimulating monocytes and lymphocytes, could then contribute to the immune system’s response against SARS-CoV-2.

But can BCG revaccination in Brazil (1994-2004) have an impact, since the age was 6 to 13 years and this can make a difference with data from other countries without revaccination? According to Dr. Mello, the literature suggests that the innate nonspecific immunity mentioned needs to be stimulated from time to time. But data on revaccination will be collected in the study, which will allow the analysis of this factor. Finally, she warns that at this time, there is no indication of vaccination of the general population with BCG for the prevention of COVID 19 and that it will be necessary to wait for the results of the studies being conducted.

UFMG develops vaccine based on the use of recombinant BCG

Researchers from the Federal University of Minas Gerais (UFMG) in partnership with the Federal University of Santa Catarina and the Butantan Institute-SP are also using the tuberculosis vaccine to develop an immunizer against COVID-19. The idea is to have a double vaccine to protect against both diseases. The team’s work involves cloning the genes of the SARS-CoV-2 virus so that the bacteria can produce them. The main advantages, if the immunizer can actually be developed, is the safety of the vaccine and BCG’s ability to protect against heterologous diseases by the phenomenon of trained immunity. Animal testing should begin only at the end of the year and there is still no forecast for human testing.

Quartet bets on BCG

Brazil, Australia, Spain, the Netherlands and the United Kingdom have decided to test the BCG vaccine in an attempt to verify whether it can be effective and safe in treating the viral disease. The vaccine will be tested on 10 thousand health professionals in various parts of the world in a phase III study. In Brazil, it will be reapplied to 2 thousand volunteers in Campo Grande, Mato Grosso do Sul, and 1 thousand volunteers in Rio de Janeiro under the coordination of Fiocruz researchers, Dr. Julio Croda and Dr. Margareth Dalcolmo.

This is the largest phase III study that analyzes the efficacy to assess whether BCG has an impact on the incidence of infection, hospitalizations and deaths associated with COVID-19. Health workers older than 18 years without previous infection can participate in the study, as well as residents in Rio de Janeiro and Campo Grande. Interested parties should pre-register at the link: https://servicos.matogrossodosul.fiocruz.br/redcap/surveys/?s=WCEMCKLK97. The study is expected to begin in Brazil this October and accompany volunteers for one year.

Professor Croda points out that there is still no evidence that BCG is effective against COVID-19, nor how long it keeps human beings immune against other respiratory diseases. “For this reason, people should not take the vaccine believing that they can avoid the new coronavirus, and it is necessary to wait for the final results of the phase III study”, he argues.

Other countries have also decided to test the BCG vaccine against the new coronavirus. This is the case of Mozambique. The Manhiça Research and Health Centre, Maputo province, will study the effectiveness of the vaccine used against tuberculosis in the country. The Netherlands is another country following suit. Scientists have begun an experiment at 22 school hospitals across the country on the impact of the tuberculosis vaccine on vulnerable elderly people to establish whether it offers protection against COVID-19.