Latent TB and COVID-19: Friends or foes?

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TB bacteria under Scanning Electron Microscope (Credit: NIAID/creative commons CC by 2.0)

 

The overall death toll due to COVID-19 has been much lower in India so far, compared to many of the other countries. This could be due to several factors. Recently, it has been suggested that BCG, a live-attenuated vaccine used against tuberculosis, might confer protection against COVID-19. This topic is being debated heavily since India has implemented universal BCG vaccination for a very long time.

However, this article is about another equally important but mostly underestimated factor, which might also play an important role in immunity against COVID-19: latent tuberculosis infection (LTBI).

According to the World Health Organization, LTBI is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifest active TB. What this means is that many people who get infected with Mycobacterium tuberculosis, the bacterium that causes tuberculosis, do not develop the disease. Only a small percentage of these infected individuals actually go on to develop symptoms. In the rest, the bacteria will enter a state of dormancy or “slumber”. However, the sleeping bacteria can occasionally wake up and stimulate an immune response. On the one hand, this can confer protection against other, unrelated diseases. But it can also induce chronic inflammation, which can make people more susceptible to metabolic diseases such as diabetes and hypertension.

In India, more than one third of our population has latent TB infection. This is one of the reasons why we are unable to completely eradicate tuberculosis.

Why is latent TB relevant under the current circumstances?

A recent study from China, which has not been peer-reviewed yet, has shown that patients with latent TB had a higher risk of contracting COVID-19 infection and their symptoms were found to be more severe. If this turns out to be true, then India might face a great increase in the number of COVID-19 infections, given its large latent TB burden. The study, however, has several drawbacks. It was conducted only on 36 COVID-19 patients, which is a very small sample size.

India falls under the tropical zone, which generally has a greater burden of infectious diseases compared to countries which are farther away from the equator. Populations that inhabit tropical countries have to deal with higher infection loads, and are constantly under the pressure of natural selection for genes which ensure better immunity. As a result, many people living in tropical countries might be able to resist infections better, even if not completely eliminate them. Recent genetic studies suggest marked differences in the expression of genes linked to the immune system between populations which inhabit tropical versus subtropical zones.

This is where LTBI finds importance. Could it contribute to any potential herd immunity against COVID-19? We do not know yet. But if this was hypothetically true, it brings up an interesting question.

How could a bacterial infection, which is dormant no less, confer protection against a viral infection?

Some of the studies conducted in our lab and also at other places have clearly shown better immune responses in LTBI subjects compared to those who are not infected with LTB. This means that immune cells ‒ the workhorses of our body that keep us healthy ‒ present in LTBI subjects produce more cytokines. These cytokines, which are proteins involved in cell signalling, are the major weapons used by our immune cells to fight infections. Since LTBI somehow makes our body (especially the immune cells) produce more of these chemicals, at least those infected with LTB may be better equipped to fight COVID-19.

Of course, there is also a flipside. An overload of these cytokines (called a cytokine storm) can actually damage the body and can sometimes be fatal, as seen in some COVID-19 patients. If LTBI works synergistically with COVID-19, then the consequences can be severe, as suggested in the China study. The nature of the cytokine storm and how it is modulated by an overlapping LTB infection can be a vital factor in determining susceptibility to COVID-19 infection. This is an important question that needs to be addressed immediately.

V. Aravindhan is an Assistant Professor at the Department of Genetics, University of Madras. His research focuses on studying latent tuberculosis infection in diabetes patients, among other things. Recently, in collaboration with Dr. Vijay Viswanathan (MV Hospital for Diabetes, Chennai) he completed a DBT-funded study (BT/PR5693/MED/29/585/2012) which looked at the prevalence of latent tuberculosis infection in diabetes patients. As part of this study, the immune response induced by LTBI was also studied by measuring cytokine responses. This article was written based on those observations.