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03/23/2022

The anatomy of a cure for long COVID

In the fight against long COVID—only just begun—Canada needs to be at the forefront of researching the causes for these lingering problems and not just hammering away at the symptoms.

It has been estimated that long COVID impacts about 14%-to 30% of people infected with the coronavirus, leaving patients with a substantial burden of health loss affecting almost every organ and regulatory system in the body.”1

The World Health Organization defines long COVID as a condition that occurs about “three months from the onset of COVID-19 with symptoms that last for at least two months and cannot be explained by an alternative diagnosis . . .. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.”2

To date Canada has had about 3.5 million COVID-19 infections. To put this in perspective, there are about 38 million people in Canada, so about 9% of Canadians have had COVID-19. This is likely an underestimation of actual infections—but even with this conservative number, at least 500,000 to 1 million Canadians may have long COVID.

Read: Long COVID: For the 1 in 10 patients who become long-haulers, COVID-19 has lasting effects

So what can be done to help the growing number of long COVID patients? In my previous article, Dr. Angela Cheung, a physician, professor of medicine and co-lead of several national long-COVID studies stated, Long COVID will be the post-pandemic-pandemic.” 

To manage the pandemic of long COVID, she explained that Canada needs to develop specialty clinics in provinces that facilitate national and international connections between specialists in order to provide the best care for these patients. Canada also needs to fund more research into treatments.

One crucial research area is developing treatments for the cardiovascular manifestations of long COVID. Studies have shown that it carries a substantial risk of cardiovascular disease.3“These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection . . .. Compared with those who were not infected, patients with mild disease had more than three times the risk of myocarditis, an inflammation of the heart muscle."

Since even mild COVID-19 can lead to serious cardiovascular disease, what research is needed to develop treatments? 

Read: Curiosity could be the key to long COVID

Dr. Glen Pyle, professor of Biomedical Science at the University of Guelph and a heart researcher who’s won multiple awards elegantly states, “We need to start at the beginning because this is a new disease. Effective treatments depend on knowing how the disease develops and create therapies that specifically target the problem, not the symptoms.

The question is, which pathways is COVID-19 using to cause the heart injury in the long run? If you dont know the pathway, and how the heart is failing, youll treat it in ways that will mask the symptoms and not treat the problem. The most effective treatment would be to identify the problem and fix that specific problem.” 

This is the crux of the issue: not all treatments are equal. For example, treating a fever makes a patient feel better, but finding that the cause of the fever is an infection caused by a certain bacteria and giving antibiotics, is fixing the problem. Not giving antibiotics can result in a worsening infection. 

Dr. Pyle explains that this research, Often involves smaller projects, we call them plug and play.’ That is, we know some molecules or systems are involved in other types of heart disease so lets see if theyre involved here. Which pathways are we looking at?

We think what happens is theres an injury to the heart. Theres not a lot of evidence that the virus itself infects the heart muscle cells. Its probably the immune response to the virus that causes the damage. The immune system becomes quite active fighting the virus and may do some damage to the heart. When heart muscle cells die, for all intents and purposes they’re gone and replaced with scar tissue. The scar tissue prevents the heart from rupturing, but it doesn’t contract as well as muscle tissue, so it puts a load on the heart. Other muscle cells grow larger to compensate but the muscle isn’t as well constructed as it should be—it cant contract as effectively. The heart tries to compensate but it cant do it properly and in the long-term we may see heart failure develop.” 

Read: We've got to get on top of long COVID before it drowns us

So, why do people with mild COVID-19 still develop cardiovascular complications?  

The analogy is someone who has a smallheart attack,” he says “Once the damage occurs the heart fixes the injury by making scar tissue. This starts a cycle where the repair doesnt actually fix the problem and instead causes a bit more dysfunction, until eventually you end up with heart failure. With COVID-19, a little bit of damage can grow over time and can end up in the same place. Heart failure is a disease that feeds on itself.”

Certainly, after understanding how heart damage progresses in both serious and mild cases of COVID-19 to create long-COVID heart failure, one can see why Dr. Pyle sees discovering the pathway by which the heart is damaged as crucial to developing a treatment. Which prompts the question, how do you find the pathway? 

We have heart samples from animals infected with SARS-CoV2,” said Dr. Pyle. We are screening them for known markers of injuries—pathways that cause heart damage and, eventually, heart failure.”   

This sounds promising, so what results did he obtain?

“It was a small project because we had samples and know the pathways,” said Dr. Pyle. “We put in a request for funding for $50,000. They were looking for larger projects and felt it wasn’t worth their time.”

This is a disappointing response from the national funding bodies in Canada, a country that has long been known for funding basic research: these are often smaller projects that provide the crucial building blocks for understanding diseases. Recently, we have seen a move to fund more applied research, that is, research that is focused on treatments. However, we can’t develop effective treatments until we understand a disease because, as Dr. Pyle explained, we are only treating symptoms not stopping disease progression. 

The need for research into mechanisms of injury is being recognized by other countries. Dr. Svati Shah, chair of the Research Committee at the American Heart Association, explains that, "We dont understand why some people are susceptible to long COVID or what the mechanisms are or why long COVID might develop," and to help figure this all out, the American Heart Association is investing $10 million in research starting April, 2022.4

It’s time Canada robustly supported basic science again. Long COVID is a new disease and basic research is the engine for developing treatments that can actually help patients. Long COVID patients deserve more than having their symptoms treated. They deserve having Canadian research expertise be laser focused on the causes and using this information to develop cures. 

Dr. Mary Fernando is a physician in Ottawa. Find her on Twitter @MaryFernando_.

References: 

  1. Long-Haul COVID Cases Could Spike after Latest Wave
  2. WHO publishes clinical case definition for long COVID
  3. Long-term cardiovascular outcomes of COVID-19
  4. $10 Million research program to fund new studies into the long-term effects of COVID-19
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