As someone who did his whole PhD studying how viruses can cause cardiac damage, I feel like it is time to discuss this topic.

So, let’s talk about viruses, our immune system, and the vulnerability of the mammalian heart

1/ https://twitter.com/sciam/status/1300533019636371456

In vertebrates, the heart is the first organ to develop and plays critical roles in the distribution of nutrients and oxygen throughout the body.

Despite the essential functions of the heart, this organ displays limited plasticity after cardiac injury. 2/

In contrast with some amphibians and eg zebrafish, the cardiomyocytes (muscle cells) found in the adult mammalian heart possess extremely limited regenerative capacity.

Huh? This means cardiac muscle cells rarely ever undergo mitosis. If you lose them, they don’t come back. 3/

So, if you think about it, essentially most of the cardiomyocytes you have right now are the same ones you had as a kiddo.

The exact number is highly debatable, but it is estimated that only ~1% of cardiomyocyte turnover per year in young adults. 4/

There are other cells in our body with poor generation potential. However, cardiac cells are, for example, not protected by physical barriers (e.g. no blood-brain-barrier-like structure) and are exposed to essentially any microbe that has access to the blood. 5/

‘Viral myocarditis’ is broadly defined as damage and inflammation of the myocardium, the muscle tissue of the heart, as a result of a viral infection.

It often resolves, but it can progress to more severe conditions such as dilated cardiomyopathy and even heart failure. 6/

Myocarditis is recognized as one of the leading causes of sudden death in young adults and found in ~10% of patients with unexplained heart failure.

Because it often resolves w/o clinical manifestations, the epidemiological data come mainly from post-mortem biopsies. 7/

Classically, the cases of sudden death are associated with young adults that are highly active (eg athletes) — likely because of the high cardiac output needed for those activities.

Yet, many of y’all reading this rn have had a cardiac viral infection w/o knowing it. 8/

Myocardial impairment is typically the result of a synergistic coalition between the loss and insufficient regeneration of cardiomyocytes.

Viruses in the heart isn’t something new. In North America and Western Europe, viruses are the most common cause of viral myocarditis. 9/

Historically, enteroviruses & adenoviruses have been the most frequently identified viruses in post-mortem studies. But many others such as parvovirus B19, herpesvirus 6, hepatitis C virus, and Epstein-Barr are commonly found. Plus, ~25% cases show co-infection w 2+ viruses. 10/

The limited mitotic activity displayed by cardiomyocytes in the heart would imply that cells that are lost during myocardial injury are virtually incapable of regeneration from existing myocytes to the extent of the original make-up of the heart.

But, what causes damage? 11/

It depends on the virus. Both direct cytopathic effects by the virus (virus kills infected cell) and/or by secondary immune-mediated pathologies (our immune cells destroy the infected cell — a problem for the heart) have been associated with the loss of cardiomyocytes. 12/

What happens after ? In most cases, another cell type, the cardiac fibroblast, takes over the space left by the lost cardiomyocyte. The end result is “scar tissue” similar to what happens in other tissues.

So, what’s the problem then? 13/

These cells will never be cardiomyocytes. They differentiate into ‘myofibroblasts’ with characteristics of a cardiomyocyte (eg some beating) — but will never be the same. If you have a skin scar, you can appreciate differences in eg elasticity compared to the unscared tissue. 14/

Back to viruses: what makes it so that a virus can damage the heart?

The answer is complicated and depends on both properties of the virus and the host. I spent a few years studying how diff strains of the same virus differ in their ability to damage the heart. 15/

Even for the case of a single virus studied, we found that genetic differences between viral strains, cardiac-specific innate antiviral differences, cardiac cell type-specific responses within the heart, and others all dictate the outcome of a cardiac viral infection. 16/

This is just me saying: the outcome of a cardiac viral infection depends on many variables. The heart is a complex organ that relies on intercellular communication between its cell types, and any virus that messes up this balance will have an impact whether acute or chronic. 17/

So, back to COVID19. It is not surprising to see cardiac damage even in asymptomatic infections because of the nature of the disease itself in ‘resolving’ acutely. If this wasn’t the case, we would all be dead by now as viruses have been infecting our hearts for awhile now. 18/

This does not mean there won’t be any long-term effects such as abnormal heart rhythms etc, and we are starting to see those effects (again, especially in athletes.)

Unfortunately, many of the symptoms are hard to distinguish from eg respiratory issues until it is too late. 19/

Lastly, why do I think we are seeing so many cases of myocarditis in COVID19 patients? (1) the lungs/heart relationship, (2) we know what to look for prior to a biopsy, (3) the affected population matches epi data, (4) virus has access to the heart, (5) it’s a pandemic. 20/

TL;DR — Viral myocarditis isn’t new. We are seeing a lot of COVID19 patients dispaying cardiac complications, particularly in young athletes. It’s difficult to pinpoint the root of SARS2 and myocarditis because many viral and host factors determine disease outcome. 21/end