BCG vaccine may prevent long covid: why and what can we learn?

At the beginning of the pandemic, researchers have tried several strategies to fight against acute Covid-19, which was incredibly severe initially.

Quite soon, authors have hypothesized that the BCG vaccine (the far-to-be-perfect vaccine used to prevent severe forms of Tuberculosis) might have helped in preventing severe Covid-19 in infected people. The reasons behind this approach was that the bacille Calmette-Guérin (BCG) vaccine has has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. However, in the largest trial so far, although performed when severe covid was less frequent, BCG failed to reduce the risk of severe infection.

Honestly, I was not surprised, since I thought the immunemodulatory effects may have had other more subtle benefits, more on the development of chronic immune mediated conditions, like long covid.

And, a team thought about that as well.

This team has reported the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19.

This was a Double-blind, placebo-controlled, randomized (1:1) clinical trial. Intervention: BCG intradermal vaccine and placebo. Patients: A total of 157 BCG and 142 placebo recipients participated in the 6-month follow-up, and 97 BCG and 95 placebo recipients participated in the 12-month follow-up. Measurements: Long COVID symptoms and mechanistic analyses.

BCG reduced hearing problems at 6 months (odds ratio [OR] = 0.26) and sleeping, concentration, memory, and vision problems at 12 months (OR = 0.45, 0.36, 0.38, and 0.36, respectively). Sensitivity analyses confirmed that long COVID-19 symptoms were reduced at the 6- and 12-month follow-ups (p = 0.010 and 0.031, respectively). BCG's crossover interaction paradoxically increased hair loss in women and decreased it in men at 6 months (p = 0.032).

Authors’ Conclusion: Long-term follow-up of the BATTLE trial participants revealed that BCG protects against long COVID development if administered within the COVID-19 convalescence period.

This is perfectly in line with also other studies documenting that antiviral treatment during the acute infection reduces the risk of developing long covid. Briefly, helping the immune system in clearing the infection as much as possible following acute infection seems more and more to help in preventing long covid. This happened also with the metformin trial (see my previous posts). Basically, all these data go in the direction of the virus being the trigger of the events that characterizes long covid.

While interesting, practical questions about the BCG findings are:

• how can people have access to BCG in the covid convalescent phase? The vaccine is not easily available in most countries

• is it helpful also if used a bit later after convalescent phase?

• May it be a usefult therapeutic approach for those patients that have already developed Long Covid?

• Should it be used maybe in those patients that during the acute infection have a higher risk of developing long covid?

• is it also useful for ME/CFS? Well, someone tried it on himself and that has helped a lot"

Herbert Renz-Polster thinks that yes, BCG might help in most of these scenarios and should be tested more and more!

Given those questions, I think it is not likely that, in the short term, BCG will be used as a tool to prevent long covid, also for “marketing” reasons, more interest will focus on antivirals. However, this study remains of significant importance because further reinforce the importance of helping the human body to clear up viral infections to prevent long term consequences.