Is there a way to tame the Covid virus?

NK Ganguly/Suparno Chakrabarti | Updated on April 29, 2021

Help at hand Mycobacterium W has been found useful in treating critically ill Covid patients   -  REUTERS

Use of immuno-modulator like Mycobacterium W could be an effective method till vaccines achieve herd immunity

The emergence of mutations of SARS-CoV-2 from the UK (B.1.1.7), South Africa (B.1.351), Brazil (P.1 lineage) and then California (B.1.427 and B.1.429) and now in India (B.1.617 and reports of a triple mutant) are worrisome in the war against Covid-19 as they spread infections faster and also escape neutralising immune response following disease or vaccine. Various strategies are being explored by scientists around the world to overcome this challenge. Harnessing the power of innate immunity is one of them.

The development of infection is dependent on characteristics of the infective agent and the host. Infection management is directed to the pathogen (infective agent) or the host. In the absence of effective anti-infective agent against a particular pathogen like smallpox, polio, measles and SARS-Cov-2, emphasis for management is based on host-directed therapies. Host-directed therapies in the form of boosting of host immune system is a well-known effective measure. Vaccines are the best example of host-directed therapy. Effective vaccination strategy is responsible for eradication of smallpox and elimination of polio.

Vaccines produce protective antibodies against vaccine specific pathogen and thereby provide protection. This is known as “adaptive” immunity of the body. Adaptive immune response requires exposure to a pathogen (virus or bacteria) or a pathogen specific vaccine for generation of antibodies. Adaptive immunity takes a few weeks to develop after exposure to a vaccine or a pathogen and is specific. Its efficacy is variable against subsequent mutants. This is best demonstrated by the influenza vaccine and needs vaccination each year with appropriate change to take care of changes in circulating strains.

Innate immunity

Innate immunity is the other type of immunity. It is the first defence mechanism that gets activated quickly (within hours) on entry of a pathogen such as SARS-CoV-2 virus. Since it recognises conserved patterns of pathogen as “non self”, it does not need previous exposure to pathogen to mount the response for destroying them and its efficacy does not change with development of mutants. Humans primarily rely on innate immunity for protection from infection by novel pathogen like SARS-CoV-2.

Unlike antibodies, the innate immune system activates macrophages and natural killer (NK) cells to fight the pathogens. They achieve this by various mechanisms including release of chemokines and cytokines.

Macrophages are the most efficient immune cells to engulf pathogens and destroy them. They also play a key role in generating pathogen specific immunity by presenting them to the adaptive immune system. NK cells directly attack the virus infected cells like T cells, without the need for priming. Such properties of innate immunity offer protection on exposure and prevents infection during pandemic with novel pathogens like Covid-19. Innate immune response under normal circumstances is well balanced. Its dysregulation leads to a cytokine storm, which makes patients significantly sick requiring ICU care. This is seen in severe Covid-19.

Immuno-modulators modulate the immune system by either stimulating or suppressing it. They are used in a variety of conditions like inflammation, cancer, and infections. Immuno-modulator like dexamethasone and tocilizumab induce immuno-suppression. Both have been used in the management of critically ill Covid-19.

Mycobacterium W (also known as Mycobacterium Indicus Pranii and commercially available as Sepsivac) is a unique indigenous immunomodulator. It is a potent stimulator of innate immune response. It also balances dysregulated innate immune response, without inducing immunosuppression. Based on its unique properties, it was developed for reducing morbidity and mortality of gram-negative sepsis under NMITLI programme of the Council of Scientific and Industrial Research (CSIR) and is approved for same. It is approved in India as an adjuvant to addition to standard of care in gram negative sepsis. Cytokine storm and associated changes seen in Covid-19 are identical to changes seen in gram negative sepsis.

Looking at similarities between the two, it was also evaluated successfully in critically ill patients with Covid-19 again under the NMITLI programme. In a recent article in a peer reviewed journal of the European Respiratory Society, administration of Mycobacterium W with standard of care offered huge benefits — faster clinical recovery with 30 times (Odds) better recovery on Day 14. This was also associated with reduction in ICU days, faster viral clearance and early discharge from the hospital. The study was conducted at leading hospitals across India including AIIMS Delhi, AIIMS Bhopal, AIIMS Raipur and PGIEMR, Chandigarh.

Being a potent stimulator of immune response, Mycobacterium W is also found useful in various infections. It is also found to provide protection against Covid-19.

In “high risk” population of workers caring for Covid-19 patients in hospital setting and also in a larger field trial its protective efficacy against development of symptomatic Covid-19 was found to be 93 per cent (p =0.0001) in health workers (HCWs) following administration of 0.2 ml.

In a field trial, protective efficacy against development of symptomatic Covid-19 following administration of 0.1 ml was found to be 70.3 per cent. Both these studies provide a real-life evidence of protective efficacy of Mw against development of symptomatic Covid-19.

As the war against Covid-19 hots up, use of immuno-modulator like Mw could prove to be an easy, quick and effective strategy until specific immunity from the vaccines provides the critical level of herd immunity to halt its transmission. Administration of Mycobacterium W to critically ill as well as those prone to get infected might be an immediate solution in flattening the rising Covid- 2.0 curve.

Ganguly, is Former Director General – Indian Council of Medical Research, and Chakrabarti is Head, Dept of Blood and Marrow Transplantation and Hematology, Dharamshila Narayana Superspeciality Hospital

Published on April 29, 2021

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