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Maybe we should think of Covid-19 as a heart disease.

When SARS-CoV-2 virus was added to human heart cells grown in lab dishes, the long muscle fibers that keep hearts beating were diced into short bits, alarming scientists at the San Francisco-based Gladstone Institutes, especially after they saw a similar phenomenon in heart tissue from Covid-19 patients’ autopsies. 

Their experiments could potentially explain why some people still feel short of breath after their Covid infections clear and add to worries that survivors may be at risk for future heart failure. 

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The new study was posted as a preprint on bioRxiv, meaning it has not yet been peer-reviewed or otherwise vetted by a scientific journal. The authors said they felt an urgent need to share their work so others could help them understand the mechanisms causing heart damage and work on ways to prevent or treat it.

“When we saw this disruption in those microfibers, … that was when we made the decision to pull the trigger and put out this preprint,” said Todd McDevitt, a senior investigator at Gladstone and a co-author of the study. “I’m not a scientist who likes to stoke these things [but] I did not sleep, honestly, while we were finishing this paper and putting it out there.” 

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His colleague Bruce Conklin, a senior investigator at Gladstone and a co-author, said the “carnage in the human cells” they saw was unlike anything that’s been previously described with other diseases. “Nothing that we see in the published literature is like this in terms of this exact cutting and precise dicing. We should think about this as not only a pulmonary disease, but also potentially a cardiac one.”

Looking like they were surgically sliced, fiber fragments known as sarcomeres bore no resemblance to the disintegration seen in other acquired or hereditary diseases of the heart muscle, the scientists said. And in another mystery, there were black holes where DNA should have been in the nucleus of these cells, leaving just an empty shell. Their observations were made using high-magnification imaging to capture what happens in the first 48 hours after exposure to the virus that causes Covid-19. 

The scientists first presented small amounts of virus to three types of human heart cells derived from stem cells: cardiomyocytes, cardiac fibroblasts, and endothelial cells. Only cardiomyocytes — the muscle cells — showed signs of viral infection that spread to adjacent muscle cells. They then obtained autopsy specimens from three Covid-positive patients and saw similar, though not identical, changes. 

Together, the sarcomere and DNA damage caused by infection could explain earlier findings of heart damage as well as case reports of lingering weakness in patients who recovered from even mild Covid-19 — if they hold up to further scrutiny and are confirmed in more patient samples.

I think it’s really important and elegant work, helping to define the potential mechanisms by which SARS-CoV-2 is leading to the observed heart damage and clinical manifestations,” said Gregg Fonarow, interim chief of the UCLA Division of Cardiology and director of the Ahmanson-UCLA Cardiomyopathy Center. “There was a real question, other than just a few case reports, as to whether the heart muscle cells themselves could be infected. This shows that at least in vitro, that absolutely can occur and that those cells engender a response that is damaging and disruptive to those cells.”

Gladstone_Comparison
Healthy heart muscle (left) has long fibers that allow the muscle to contract. SARS-CoV-2 infection dices up these fibers (right), which can harm the cells’ ability to beat. Gladstone

Caveats abound when extrapolating from lab-dish studies with human cells to patients, but the striking cell culture images add to a limited but growing body of evidence from autopsy reports and clinical studies of hearts in people infected by SARS-2. Balancing the “only in cell culture” limitation is one advantage of studying infection in a dish: Scientists can watch one possible causal factor at a time in isolation, rather than trying to tease out what’s happening during a viral infection that finds its way into every system in the body. Is it inflammation? Is it pulmonary stress? Did the patient have previous heart damage?

“This is the virus itself damaging the heart,” said UCLA’s Fonarow, who was not involved in the research. “There are no other ones in that test tube. There is no systemic inflammation.” 

Sahil Parikh, an interventional cardiologist at Columbia University Irving Medical Center who was not involved in the Gladstone study, says the jury is still out.

“The data are provocative: It suggests that cardiomyocytes, the heart muscle cells, in a Petri dish are damaged in ways that are potentially irretrievable,” he said. “The challenge here is that this paper has not been peer-reviewed by people who are experts in cardiology, who have not had a chance to tear it apart. I am reluctant to make a lot out of a pre-publication manuscript, no matter how provocative the finding.” 

The Gladstone scientists concede the need for outside experts, and they have submitted the manuscript to a leading journal. Since the pandemic began, doctors and basic scientists have been documenting how the virus — initially viewed as primarily a respiratory illness — reaches into many parts of the body, from the nose to the toes. It can trigger an overwhelming immune response called a cytokine storm in some people, multisystem inflammation in some children, neurological problems, and abnormal blood clotting in the brain, heart, and lungs. 

Concern about long-term damage to the heart stems from the fact that unlike the liver, for example, it cannot regenerate its tissues. Doctors in Germany reported earlier this summer that 39 autopsies and cardiac MRIs of 100 patients showed damage to the hearts of older people who died (average age of 85) and younger people (average age of 49) who weren’t even hospitalized for their apparently mild Covid-19 infections. 

The cardiac MRI study has since been corrected to amend statistical errors, but Fonarow, who co-authored an editorial that accompanied the two articles published in July in JAMA Cardiology, said the main message of heart damage still held true, raising the specter of heart failure for patients as they grow older and their hearts become weaker.

Patients who heard about that German study are asking for cardiac MRIs, Parikh said. 

“We worry that those patients who did demonstrate heart damage during the acute illness, or in the near term afterward, may have long-term sequelae that they will not recover from,” he said. “Many patients are just anxious and come to get checked out. To say there’s a clear pattern of acute and then chronic convalescent heart disease would be premature.”

The Gladstone scientists still don’t know if the heart can reassemble sarcomeres once they’ve been cut, perhaps after the infection clears. The heart cells in the three autopsy samples they studied looked different than what they saw in the lab dish 48 hours after exposure to the virus. In the patient samples, there were just hints of a disorderly rearrangement of the muscle fibers, Conklin said.

To learn more, the scientists said, autopsy data need to tell more of the story than current post-mortem exams do. They think that problem can be solved with available immunohistochemistry tests that can detect the sarcomere disarray they’ve seen in their experiments.

For patients actively fighting Covid-19 infections, there is a highly specific test that shows damage to heart muscle. Widely used when a heart attack is suspected, the blood test looks for troponin, which leaks into the blood when heart muscle dies. 

Conklin and McDevitt hope their work will pave the way for discovering drugs that might target an as-yet-unidentified enzyme in the virus that so efficiently slashes the sarcomeres. They propose high-throughput screening of available drugs that could possibly benefit patients, using an assay they developed. Further research would establish a timeline for when to intervene, which could be early in infection. 

Different heart medications are being tested to see if they can protect the hearts of Covid-19 patients, including drugs designed to lower blood pressure or treat diabetes, UCLA’s Fonarow said. And Columbia’s Parikh points out that there are treatments to help people whose hearts aren’t pumping strongly. 

Just because the heart isn’t squeezing well now doesn’t mean it can’t improve its squeezing function with appropriate medical therapy,” Parikh said.

Gladstone’s Conklin thinks of his late father, who had scarlet fever and strep throat in the 1930s, before the advent of antibiotics. He suffered heart valve damage that didn’t bother him for most of his life, but it did eventually “take him down” in his 80s. 

“Fifty years from now, what are we going to be seeing?” Conklin asked.

  • Other research shows the concurrent Bradykine Storms to the Cytokine Storms explaining the whole body system reach and damage. I’d like to see these results studied side by side.
    “A Supercomputer Analyzed Covid-19 — and an Interesting New Theory Has Emerged. A closer look at the Bradykinin hypothesis” Thomas Smith

  • Hi, my boyfriend, 32yo, got covid last March. He didn’t need hospitalisation, but after a few weeks in which he felt better, he developed more symptoms. He’s been diagnosed with POTS in June and still hasn’t recovered. He did chest X-ray and CT scan, and everything looked normal, but not an MRI. Are those tests enough to exclude a heart damage? He was prescribed ivabradine, but stopped taking it since he felt it was hiding symptoms (he had a relapse of fatigue and headaches after he started to go for slow walks every day). He also has irregular beats when the heart rate goes above 105/110. What would be the advice for him?

    • I can only speak to the nutritional aspects of recovery for your boyfriend: make sure he’s getting a minimum of 5,000 IU of Vitamin D3 per day. Every single cell in the body has D receptors and Covid19 depletes Vitamin D. This supports the immune system and helps prevent inflammation.

  • Curious as to whether anyone is looking at potential damage to the reproductive systems. Are we going to have a large increase in infertility and impotence in the future?

  • My opinion based on many decades of experienced with life. Travelled the world seen the environmental blight of too much development and excessive greed. Nature is giving the human species warning signs that we are on a suicidal path. Collectively humanity is too ignorant to see the big picture unfolding. It is a restless world of selfish denial. Politicians are hopelessly useless in understanding the deeper awareness as to what is happening, they dance to the tune of forever progress.
    Jardey
    A realist who sees the madness of a restless world.

  • I’d like to find out if it was made in a lab. I’m thinking it was since it seems to have a greater affinity for humans than animals.

    • You GREATLY exaggerate humans’ ability to design & build things like this. Look at all the modalities it has, and after 8 months of intense study by tens of thousands of the best human minds in this field, we really have a clue as to how only one or two of them work.

      For instance … and this is something REALLY fundamental and probably quite simple … the virus disables the interferon messaging to the immune system, we understand that … and then after a sufficient interval of time, it reveals itself and millions of its siblings. EXACTLY HOW does the virus manage to delay this for a couple of weeks?
      If this was “designed”, it was by either God or Darwin’s spirit, or aliens looking to eradicate the plague of humans. NO HUMAN IS CAPABLE OF DESIGNING SUCH A THING.

  • This information is worthless without at least a good number of before/after studies in vivo. The hype around athletes with myocardia totally ignores, for example, the growing literature on mixing steroids with aspartame leading to so-called “sudden death syndrome” in seemingly perfectly fit young athletes. Add the fatality rate of covid amongst diabetics and the elderly, and one has to ask: was myocardia really a consequence, or (just) the cause? This said in the firm conviction that aspartame and similar is a biochemical disaster that provably leads to both diabetes and heart problems, amongst many other things. I beg the anointed professionals to investigate that side of this issue.
    In the end, the original promise of this (designed) virus was as carrier of vaccine-strain RNA, has Frankenstein’s monster escaped?

  • Shortly after birth human cardiomyocytes (heart muscle cells) stop dividing. Rather than continuing to divide the cells simply get bigger as we age allowing the heart to grow. Once the SARS-CoV2 virus destroys some fraction of these cells the remaining cells will begin to enlarge further (hypertrophy). This increases stress and leads to further cell death and dysfunction. This vicious but not virtuous cycle is exactly what happens after a heart attack. If true in vivo these data suggest that many if not the majority of COVID-19 patients may have sequalae simular to patients who suffer myocardial infarctions (heart attacks).

  • We also have.. Dr. Eric Topol, a cardiologist and director of the Scripps Research Translational Institute in La Jolla, California who said ”it goes after the heart.. ” and now we note how.. thanks to these docs. .. Dr. Topol.. “We thought this was only a respiratory virus. Turns out, it goes after the pancreas. It goes after the heart. It goes after the liver, the brain, the kidney and other organs. We didn’t appreciate that in the begining,In addition to respiratory distress, patients with COVID-19 can experience blood clotting disorders that can lead to strokes, and extreme inflammation that attacks multiple organ systems. The virus can also cause neurological complications that range from headache, dizziness and loss of MEMORY, taste or smell to seizures and confusion”.

  • This cell damage is not surprising, as SARS-Cov-2 encodes three (!) porins (i.e. ion channel cell toxins). One of them, protein 3a, has been shown in SARS-Cov-1 to leave the protein-producing cell and to be inserted into the membranes of neighboring cells, punching holes into them. This porin function of 3a was shown to be essential for its apoptotic effects. Note also that SARS survivors had lots of antibodies against 3a.

    Regrads,
    Ralf Stephan, biocurator

    • Looks like a good job well done. From US Lawyer Dr. Stephan Boyle who drafted bio warfare legislation.. “I also went through the scientific article where the Australian health board working with Wuhan … genetically engineered HIV into SARS, that is all verified in scientific papers. In addition, it seems to me that they took that back to the [Wuhan] BSL4 and applied nanotechnology to it. The size of the molecules indicates we are dealing with nanotechnology. That’s [something]you need to do in a BSL4. Biological weapons nanotechnology is so dangerous, people working with it have to wear a moon suit with portable air … We also know that one of the cooperating institutions [to Wuhan BSL4]was Harvard, and that the chairman of the Harvard chemistry department, [Dr. Charles Lieber], a specialist in nanotechnology, set up an entire laboratory in Wuhan where [according to reports]he specialized in applying nanotechnology to chemistry and biology.
      My guess is, based on what I’ve read in the literature, that they tried to weaponize all that together. And that is SARS-CoV-2 that we are dealing with now.
      So, it’s SARS, which is genetically engineered biowarfare agent to begin with. Second, it has gain-of-function properties, which makes it more lethal, more infectious. It has HIV in there. That was confirmed by an Indian scientist … and it looks like nanotechnology [has been used]…..

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