STATNEWS: Carnage' in a lab dish shows how the coronavirus may damage the heart

[SheltieLover]

https://www.statnews.com/2020/09/04/carnage-in-lab-dish-shows-how-coronavirus-may-damage-heart/

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.

The new study was posted as a preprint on bioRxiv, meaning it has not yet been peer-reviewed or otherwise vetted by a scientific journal.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."

No wonder chumputin wants everyone in US infected!

[DFW]

1. That way, everyone can be as heartless as he is

(Sorry, I couldn't resist)

[BumRushDaShow]

2. There have been many other reports/studies that noted the coronary issues

I think why they seemingly haven't risen to the top of the reporting is because they were individually considered "limited studies". But at some point when you have dozens and dozens of "limited studies" and observations world-wide by researchers, hospitals, and medical examiners/coroners, all seeing the same thing ("in general" ), this phenomena needs to be highlighted more.

I.e., the commonly-accepted designation as a "respiratory disease" misses that it (or at least some form(s)) is more than that and in fact, suggestions have been made (again based on "limited studies" ) that the "respiratory" manifestation/presentation seems to result after an impact occurs elsewhere first before eventually migrating to the lungs.

[MaryMagdaline]

3. Good analysis

[Hugin]

4. Yeah, it's a scary thought, but, maybe this breakdown of cardiac muscle is what is occurring in the

Last edited Sat Sep 5, 2020, 09:39 AM - Edit history (2)

multitudes of people who are 'asymptomatic'.

I'm not sure what obvious symptoms this would cause in an otherwise healthy adult. Seeing the process in a patient would require imaging or diagnostics over an extended period of time and we can barely get people to take a swab.

This would also explain how the disease manifests in children as their smooth/cardiac muscle can still generally regenerate at a faster rate than older adults. Those over 50, who, when they lose smooth/cardiac muscle, never get it back. No telling if the damage is permanent in children. Especially, if there is a back and forth of viral action/regeneration going on over time in someone who has initially contracted the virus. Similar to what occurs with the Malaria parasite.

The only solution is to wear a goddamned mask and not get infected in the first place.

Some references:

https://en.wikipedia.org/wiki/Cardiac_muscle

https://en.wikipedia.org/wiki/Smooth_muscle

[BumRushDaShow]

6. One of the focuses has been on what it is able to attach to

i.e., ACE-2 receptors, and then moves on from there. I had seen this earlier - https://www.statnews.com/2020/04/10/coronavirus-ace-2-receptor/

where that (as well as an article I read yesterday that I was looking for again) basically summed it up as the virus managing to attach to wherever these receptors are (heart, lungs, kidneys, digestive system, with the above-linked article also mentioning that the nose has receptors that are of similar enough configuration to be an attaching point), and where once inside, it managed to basically McGyver substances to make less habitable parts of the body, more conducive to its further attachment and replication - notably in the lungs. And it can manifest itself to the point where the lung alveoli can become so impacted by swelling, blood clots, and mucus globules, that even with a ventilator, little O2 can actually reach the bloodstream due to the blockage from the infected sacs.

And there had been concern that those who were on ACE inhibitors for blood pressure/heart disease control, might be more severely impacted because of what COVID-19 seems to be doing - but 2 recent studies that came out last month (1 from human trials and the other done on mice) seemed to confirm that those on ACE inhibitors had little statistically significant negative impact when infected but still receiving the ACE-inhibitor meds (probably because ACE inhibitors impacts the level of ACE-1 vs ACE-2, the receptors of which COVID-19 uses).

The ACE-2 connection seems to have pretty much confirmed why the range of symptoms - breathing problems, heart arrhythmia, gastrointestinal issues, loss of taste/smell, kidney impact, where a number of patients ended up on dialysis while in the hospital, etc.

I swear - this is something I would NOT want to contract, let alone "dismiss" if "symptoms" are supposedly "mild", because it is rolling the dice on where it managed to attach itself when it got in your body and how your body will react to it, depending on the viral load. I.e., it might somehow bypass your lungs initially and end up finding dry land on your kidneys, eventually reproducing from there until it makes it to the heart or lung payload.

[Hugin]

7. I'm glad you're paying attention to these developments...

in what is turning out to be a virus that can cause irreversible damage in all areas of an organism.

I guess that's due to it's use of a multi-purpose and wide spread receptor within vertebrates (and it turns out invertebrates )

It's looking worse every day.

[BumRushDaShow]

8. Yes.

And this apparently seemed to have been known about past coronaviruses, but none to date have been as virulent as this one.

And obviously this one really "perfected" its "configuration" to maximize its abilities, which obviously fits with the "survival of the fittest" doctrine. Iterations/mutations that can't attach to a cell as effectively or long enough to replicate, will die out, being unable to get a foothold, whereas those that have a broader ability to make landfall, buy themselves enough time to replicate and survive.

And apparently most individuals have bodies that will say WTF is this?! and will send out things to start fighting it and if that fails, a certain percentage of those people have bodies that will then "throw everything its got" at it (the oft-mentioned "cytokine storm" ), resulting in killing the "host" (the person) itself when doing so because that all-hands-on-deck response kills "good" cells along with the invaders.

But now they are finding (and this is one of the articles that I saw yesterday) that in patients who end up with pneumonia, they apparently end up undergoing a "Bradykinin storm", which is something new to me seeing mentioned. I found the link to the article below from here - https://www.the-scientist.com/news-opinion/is-a-bradykinin-storm-brewing-in-covid-19--67876

A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm

Michael R Garvin, Christiane Alvarez, J Izaak Miller, Erica T Prates, Angelica M Walker, B Kirtley Amos, Alan E Mast, Amy Justice, Bruce Aronow, Daniel Jacobson Is a corresponding author

Oak Ridge National Laboratory, Biosciences Division, United States; University of Tennessee Knoxville, The Bredesen Center for Interdisciplinary Research and Graduate Education, United States; University of Kentucky, Department of Horticulture, United States; Versiti Blood Research Institute, Medical College of Wisconsin, United States; VA Connecticut Healthcare/General Internal Medicine, Yale University School of Medicine, United States; University of Cincinnati, United States; Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, United States; University of Tennessee Knoxville, Department of Psychology, Austin Peay Building, United States

Short Report Jul 7, 2020

<snip>

SARS-CoV-2 uses a human enzyme called ACE2 like a ‘Trojan Horse’ to sneak into the cells of its host. ACE2 lowers blood pressure in the human body and works against another enzyme known as ACE (which has the opposite effect). Therefore, the body has to balance the levels of ACE and ACE2 to maintain a normal blood pressure. It remains unclear whether SARS-CoV-2 affects how ACE2 and ACE work. When COVID-19 first emerged, a team of researchers in China studied fluid and cells collected from the lungs of patients to help them identify the SARS-CoV-2 virus. Here, Garvin et al. analyzed the data collected in the previous work to investigate whether changes in how the body regulates blood pressure may contribute to the life-threatening symptoms of COVID-19.

The analyses found that SARS-CoV-2 caused the levels of ACE in the lung cells to decrease, while the levels of ACE2 increased. This in turn increased the levels of a molecule known as bradykinin in the cells (referred to as a ‘Bradykinin Storm’). . Previous studies have shown that bradykinin induces pain and causes blood vessels to expand and become leaky which will lead to swelling and inflammation of the surrounding tissue. In addition, the analyses found that production of a substance called hyaluronic acid was increased and the enzymes that could degrade it greatly decreased. Hyaluronic acid can absorb more than 1,000 times its own weight in water to form a hydrogel. The Bradykinin-Storm-induced leakage of fluid into the lungs combined with the excess hyaluronic acid would likely result in a Jello-like substance that is preventing oxygen uptake and carbon dioxide release in the lungs of severely affected COVID-19 patients. Therefore, the findings of Garvin et al. suggest that the Bradykinin Storm may be responsible for the more severe symptoms of COVID-19.

<snip>

Although much focus has been on the lung due to the need for ventilator support of end-stage disease, COVID-19 also affects the intestine, liver, kidney, heart, brain, and eyes (Wadman, 2020). Nearly one-fifth of hospitalized patients experience cardiac injury (Shi et al., 2020), many of whom have had no history of cardiovascular problems prior to infection. Responses include acute myocardial injury, myocarditis, and arrhythmias (Driggin et al., 2020) that may be due to viral infection directly, which is consistent with high expression of the SARS-CoV-2 receptor ACE2 in cardiac tissue (gtexporta.org). An important extension of the RAS in controlling cardiac contraction and blood pressure is the potent inotrope apelin (APLN), which acts as an NO-dependent vasodilator when its receptor (APLNR) heterodimerizes with BDKRB1 (Bai et al., 2014). APLN (98 fold), APLNR (3190 fold) and BDKRB1 (2945 fold) are all upregulated in COVID-19 BAL. As with BK and ANG derived peptides, APLN is inactivated by Neprilysin (MME), which is significantly downregulated in the BAL samples from COVID-19 individuals (−16 fold). Therefore, increased APLN-signaling can be added to the imbalanced RAS.

In addition to cardiac dysfunction, neurological involvement in COVID-19 was revealed after an MRI assessment of COVID-19-positive patients with encephalopathy symptoms in France identified enhancement in leptomeningeal spaces and bilateral frontotemporal hypoperfusion (Helms et al., 2020) which are consistent with increased vascular permeabilization in the brain. Furthermore, earlier reports from China indicate high frequencies of dizziness, headache, as well as taste and smell impairment (Mao et al., 2020). The most recent reports from the United States and China indicate that 30–50% of COVID-19 patients experience adverse gastrointestinal symptoms (Cholankeril, 2020; Pan et al., 2020). Direct infection by the virus and damage to the kidney was also observed, specifically in the proximal tubules (Su et al., 2020). These latter two findings are not surprising given the higher expression of ACE2 in these tissues compared to tissues overall (gtexportal.org), which would facilitate infection by the virus. Finally, COVID-19 patients also frequently display skin rashes including ‘covid-toe’ that appear to be related to dysfunction of the underlying vasculature.

<snip>

https://elifesciences.org/articles/59177

[BumRushDaShow]

9. Sorry to keep on this but I finally found the article I was thinking about that had a good analogy

It was a summary of the publication of a supercomputer analysis of tens of thousands of genes & genetic data to look for correlations - https://spectrum.ieee.org/the-human-os/computing/hardware/has-the-summit-supercomputer-cracked-the-covid-code.amp.html (related to the excerpts from the paper I posted just above)

Bradykinin hypothesis in analogy -

Covid-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house. Once inside, though, they don’t just take your stuff — they also throw open all your doors and windows so their accomplices can rush in and help pillage more efficiently.

A Supercomputer Analyzed Covid-19 — and an Interesting New Theory Has Emerged
A closer look at the Bradykinin hypothesis
Thomas Smith

4 days ago·8 min read


According to the team’s findings, a Covid-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose, (The receptors, which the virus is known to target, are abundant there.) The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease’s cardiac and GI symptoms.

But once Covid-19 has established itself in the body, things start to get really interesting. According to Jacobson’s group, the data Summit analyzed shows that Covid-19 isn’t content to simply infect cells that already express lots of ACE2 receptors. Instead, it actively hijacks the body’s own systems, tricking it into upregulating ACE2 receptors in places where they’re usually expressed at low or medium levels, including the lungs.

In this sense, Covid-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house. Once inside, though, they don’t just take your stuff — they also throw open all your doors and windows so their accomplices can rush in and help pillage more efficiently.

<snip>

The end result, the researchers say, is to release a bradykinin storm — a massive, runaway buildup of bradykinin in the body. According to the bradykinin hypothesis, it’s this storm that is ultimately responsible for many of Covid-19’s deadly effects. Jacobson’s team says in their paper that “the pathology of Covid-19 is likely the result of Bradykinin Storms rather than cytokine storms,” which had been previously identified in Covid-19 patients, but that “the two may be intricately linked.” Other papers had previously identified bradykinin storms as a possible cause of Covid-19’s pathologies.

https://elemental.medium.com/a-supercomputer-analyzed-covid-19-and-an-interesting-new-theory-has-emerged-31cb8eba9d63

[Hugin]

10. Very informative.

This is a really active little wrench in the gears... This virus.

[Hugin]

5. K&R

More important than any of the Trumps.