29 July On BCG and TB

Dear colleagues,

1. There is a lot to do about the possible protective effect of BCG vaccination on COVID.  This hypothesis is based on early epidemiological evidence that COVD was/is (?)  strikingly less in parts of the world where BCG vaccination is still generalized See https://www.who.int/news-room/commentaries/detail/bacille-calmette-gu%C3%A9rin-(bcg)-vaccination-and-covid-19.  

As discussed in the papers in attachment, there is indeed ample evidence that the non-specific “training” effect of BCG on the immune system (with skewing towards Th1, activation of NK and myeloid cells, associated with epigenetic changes…) may explain experimental, but also clinical-epidemiological evidence that BCG partly protects from a range of other infections. It is even used in some cancer therapies. At this moment, there is certainly no proof that childhood BCG vaccination may have a sufficient long-lasting effect to protect against COVID and the early epidemiological associations may be explained by other factors including population structure (i.e. a younger population in the areas with less severe COVID).     

Clearly, as with the early claims on effectiveness of various drugs (cholorquine, Kaletra etc), the only way to be sure is to carry out a  randomized double blind placebo controlled trial.  These trials are underway for BCG, but obviously, they will take more time than the treatment trials.

My personal opinion is that a positive effect in a particular context is not excluded, e.g. a BCG vaccine applied to health care workers, who will be exposed to SARS-CoV-2 in the next few months, but I do not think that BCG will become a  “COVID vaccine”.

For those who are interested in this matter, please follow up on these two trials:

- Reducing Health Care Workers Absenteeism in Covid-19 Pandemic Through BCG Vaccine (BCG-CORONA) https://clinicaltrials.gov/ct2/show/NCT04328441.  

- BCG Vaccination to Protect Healthcare Workers Against COVID-19 (BRACE). https://clinicaltrials.gov/ct2/show/NCT04327206

Based on the information on the websites, the first one is more active in recruiting and it might be easy to associate, since it takes place in the Netherlands.

There are probably others….

2. Association with Tuberculosis

2.1. Descriptive paper on 49 TB/SARS-CoV-2 cases over the world:

• In 19 (38.8%) patients COVID-19 appeared during anti-TB treatment and limited or no protection against COVID-19 might have favoured SARS-CoV-2 infection
• In 9 patients the two diagnoses were made simultaneously:  Any contribution of COVID-19 to TB pathogenesis cannot be excluded or confirmed.
• In 14 patients, diagnosis of active TB was made after SARS-CoV-2: does the virus activate latent TB?
• In 7 cases  COVID-19 occurred in patients with TB sequelae, but these were aolder and 6/7 had comorbidities
• The case fatality rate was high (6/49, 12.3%); 5/6 were >60 years old and all of them had ≥1 co-morbidities.

 Given the small number of deaths, larger studies are necessary to draw any scientific conclusion….

2.2. The large study in Western Cape gives a very curious picture: TB increased the risk for COVID-related death in “all COVD cases”, to a similar extent as HIV, b ut to a lesser extent as old age or diabetes.  The strange observation is that the hazard for current TB is insignificant in hospitalized COVID patients….See Fig 1 p.21.

2.3.  A population-based study in Taiwan shows a lower incidence of TB during the COVD epidemic (which was very mild), but no decrease in HIV or HCV.  The authors ascribe this effect to all the preventive measures, which -quite logically- should decrease other airborne but not necessarily blood- or sexually transmitted infections….

So, clearly, there is some interesting work to do for those researchers who are interested in TB/BCG and COVID interactions.

Guido