Welcome to Molecular Ideas, and thank you for sharing your time with us! Today, we will explore how to leverage the unexpected relationship between tuberculosis and COVID-19 to curb our current pandemic.
Ten months into the COVID-19 pandemic, it may be easy to think that our old definition of ‘normalcy’ may never return. No matter how much we all want a mask-free world where we can commune with our loved ones, mounting case numbers and the tragic loss of life as a result of COVID-19 is a reality we must continue to bear.
With the approval of Comirnaty® (the Pfizer-BioNTech vaccine) and Moderna’s vaccine, we have a collective opportunity to manage this disease. (Until then, please wear a mask). There are plenty of self-evident learnings we can take from this pandemic to prevent a similar disease from emerging on a global scale again, ranging from geopolitical transparency, governmental preparedness, and personal protection. (Once again, please wear a mask).
As a global community, we also need to reflect on how we can manage infectious diseases when they emerge. Even in this unprecedented time, we can look to humanity’s oldest pathogen – tuberculosis – as a case study for success.
At first glance, comparing tuberculosis to COVID-19 may seem odd. After all, one is an ancient bacterium expected to have survived 70,000 years; the other is a novel virus. However, there are fundamental commonalities in how they affect us and have been managed throughout the life sciences industry, including:
1) They are masters at evading the immune system and may never register as symptomatic conditions.
2) Basic research plays a critical role since we are still learning about how to counter and manage these pathogens in the scientific and clinical communities.
3) Therapy development is being managed by a rarely-seen coalition of pharmaceutical companies, NGOs, and government agencies.
TB’s long interplay with humanity has yielded many insights into managing infectious disease. However, we continue to learn so that we can hopefully eradicate a disease that affects millions worldwide each year.
Mycobacteria tuberculosis (or 'TB' for short) is a fascinating bacterium. It is a multi-drug-resistant bacteria, most commonly known for its association with HIV and AIDS in immunocompromised patients. Similar to COVID-19, it is a respiratory disease in which up to 90% of patients can be asymptomatic (known as ‘Latent’ TB infection). The key difference between TB and COVID-19 is that TB can remain latent for years or decades at a time. TB primarily evades the immune system thanks to its waxy (‘acid fast’) cell wall and low metabolic rate driven by unique transcription factors that allow infection to persist despite antibiotic treatment. Even under optimal laboratory conditions, modern TB has an infamously slow rate of growth – sometimes as long as one month. Despite this, the pathogen evolved form fare more virulent strains. While COVID-19 is comparatively simple and a virus, the emergence of the new UK strain (VOC – 202012/01) should give us pause. When infections are active, both pathogens manifest with a variety of symptoms that move beyond the lungs; establishing the root cause of the infection can be difficult without the guidance of the disease’s prevalence in your area and personal risk factors. This makes tracking of widespread diseases that become endemic in our society all the more critical - those tasked with controlling COVID-19 in the future could learn from the integrated network of public health and academic communities that continually monitor and research tuberculosis.
With that in mind, what can we hope to continue learning about TB and COVID-19 from a basic research perspective? Quite a bit. Bastions of basic research, such as the Jacobs Lab at Albert Einstein College of Medicine and the Center for Tuberculosis Research at Johns Hopkins University continue to provide the bedrock for new therapeutics by examining the genetic and metabolic underpinnings of TB. Both labs examine the phylogenetic cousins of this ancient disease, including M. haemophilum and M. leprae (leprosy) to provide us with clues for new pathways to target in drug development. COVID-19 is not the first SARS virus we’ve encountered in recent history, and it probably will not be the last. Critical breakthroughs in clinical care and vaccine development have resulted from exploring these avenues.
Finally, patients affected by both of these diseases have an inspiring outpouring of support from industry, government, and NGOs across the world. Approximately $10 billion has been spent on COVID-19 vaccine development in the last year, to say nothing of the trillions invested to manage the broader economic implications of this disease. The all-time-high of $772 million in funding for TB research in 2017 may seem minuscule by comparison. However, over 1.6 million people died globally from tuberculosis in 2017 – which is frighteningly close to the 1.77 million who have passed away from COVID-19 infections. In both cases, new treatments are needed as soon as possible.
The speed with which we have reached this tragic milestone of COVID-19 infections has driven top ten pharmaceutical companies and innovative biotechs to restructure their commercialization priorities to address this need. However, we can learn a lot about how to manage persistent COVID-19 infection in a post-vaccine world and the emergence of new diseases by looking at how the TB community has done more with less. In addition to the expected interplay between basic research institutions and industry, there are striking partnerships between industry players and various NGOs.
With a vaccine coming, COVID-19 will hopefully soon fade from our day-to-day lives. However, this does not mean we can be any less vigilant. While industry funding will likely shift back to align with pre-COVID-19 trends, established diseases need continued and exclusive therapy support. TB Alliance offers a proven framework for successfully intersecting the interests of governments, NGOs and pharmaceutical organizations to shepherd new tuberculosis therapeutics to market. Their latest success is pretomanid, approved by the FDA in late 2019. They are working on developing new regimens to ensure that ingenuity wins out over drug-resistance. As a drug-developing non-profit organization, their goal is to keep the disease in check as long as the need exists. With the emergence of new COVID-19 strains, an organization like this can help manage industry incentives for new vaccine modalities and coverage.
Exploring diseases of the past may continue to yield clues about how to curb this pandemic – and prevent the next one.
That’s all for today! As always, leave your thoughts, ideas, opinions, and suggestions in the comments.
