COVID-19 Is a Vascular Disease: Coronavirus’ Spike Protein Attacks Vascular System on a Cellular Level

Representative images of vascular endothelial control cells (left) and cells treated with the SARS-CoV-2 Spike protein (right) show that the spike protein causes increased mitochondrial fragmentation in vascular cells. Credit: Salk Institute

Salk researchers and collaborators show how the protein damages cells, confirming COVID-19 as a primarily vascular disease.

Scientists have known for a while that SARS-CoV-2’s distinctive “spike” proteins help the virus infect its host by latching on to healthy cells. Now, a major new study shows that they also play a key role in the disease itself.

The paper, published on April 30, 2021, in Circulation Research, also shows conclusively that COVID-19 is a vascular disease, demonstrating exactly how the SARS-CoV-2 virus damages and attacks the vascular system on a cellular level. The findings help explain COVID-19’s wide variety of seemingly unconnected complications, and could open the door for new research into more effective therapies.

“A lot of people think of it as a respiratory disease, but it’s really a vascular disease,” says Assistant Research Professor Uri Manor, who is co-senior author of the study. “That could explain why some people have strokes, and why some people have issues in other parts of the body. The commonality between them is that they all have vascular underpinnings.”

Salk researchers collaborated with scientists at the University of California San Diego on the paper, including co-first author Jiao Zhang and co-senior author John Shyy, among others.

While the findings themselves aren’t entirely a surprise, the paper provides clear confirmation and a detailed explanation of the mechanism through which the protein damages vascular cells for the first time. There’s been a growing consensus that SARS-CoV-2 affects the vascular system, but exactly how it did so was not understood. Similarly, scientists studying other coronaviruses have long suspected that the spike protein contributed to damaging vascular endothelial cells, but this is the first time the process has been documented.

In the new study, the researchers created a “pseudovirus” that was surrounded by SARS-CoV-2 classic crown of spike proteins, but did not contain any actual virus. Exposure to this pseudovirus resulted in damage to the lungs and arteries of an animal model—proving that the spike protein alone was enough to cause disease. Tissue samples showed inflammation in endothelial cells lining the pulmonary artery walls.

The team then replicated this process in the lab, exposing healthy endothelial cells (which line arteries) to the spike protein. They showed that the spike protein damaged the cells by binding ACE2. This binding disrupted ACE2’s molecular signaling to mitochondria (organelles that generate energy for cells), causing the mitochondria to become damaged and fragmented.

Previous studies have shown a similar effect when cells were exposed to the SARS-CoV-2 virus, but this is the first study to show that the damage occurs when cells are exposed to the spike protein on its own.

“If you remove the replicating capabilities of the virus, it still has a major damaging effect on the vascular cells, simply by virtue of its ability to bind to this ACE2 receptor, the S protein receptor, now famous thanks to COVID,” Manor explains. “Further studies with mutant spike proteins will also provide new insight towards the infectivity and severity of mutant SARS CoV-2 viruses.”

The researchers next hope to take a closer look at the mechanism by which the disrupted ACE2 protein damages mitochondria and causes them to change shape.

Reference: “SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2” by Yuyang Lei, Jiao Zhang, Cara R. Schiavon, Ming He, Lili Chen, Hui Shen, Yichi Zhang, Qian Yin, Yoshitake Cho, Leonardo Andrade, Gerald S. Shadel, Mark Hepokoski, Ting Lei, Hongliang Wang, Jin Zhang, Jason X.-J. Yuan, Atul Malhotra, Uri Manor, Shengpeng Wang, Zu-Yi Yuan and John Y-J. Shyy, 31 March 2021, Circulation Research.
DOI: 10.1161/CIRCRESAHA.121.318902

Other authors on the study are Yuyang Lei and Zu-Yi Yuan of Jiaotong University in Xi’an, China; Cara R. Schiavon, Leonardo Andrade, and Gerald S. Shadel of Salk; Ming He, Hui Shen, Yichi Zhang, Yoshitake Cho, Mark Hepokoski, Jason X.-J. Yuan, Atul Malhotra, Jin Zhang of the University of California San Diego; Lili Chen, Qian Yin, Ting Lei, Hongliang Wang and Shengpeng Wang of Xi’an Jiatong University Health Science Center in Xi’an, China.

The research was supported by the National Institutes of Health, the National Natural Science Foundation of China, the Shaanxi Natural Science Fund, the National Key Research and Development Program, the First Affiliated Hospital of Xi’an Jiaotong University; and Xi’an Jiaotong University.

Cell BiologyCOVID-19Infectious DiseasesMolecular BiologyPopularSalk Institute
Comments ( 45 )
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  • David D. Walgenbach

    Some one in the scientific community must comment on the joint sites of cooperation
    of the research and the varied nationality of the scientists working on the project!

  • Willam

    And what about those many numbers in the total population who contract the virus, recover with seemingly little damage if any to their vascular system? Are their other unknown factors that give them natural immunity?

  • Richard Alexander

    I’m wondering what this research implies about mRNA vaccines that stimulate the production of spike proteins. Would these vaccines not cause similar harm?

    • That Guy

      It would be nice for them to address it, but given millions vaccinated, apparently not

      • Star Bailey

        I feel like there are a lot of propagandists showing up in the comments here. They say things like “vaccines are perfectly safe” which everyone knows is a blatant lie. Vaccination is a calculated risk and with tried and true vaccines the risks are very rare, but no vaccine is “safe” in that deaths and injuries occur due to allergies, negligence and medical incompetence. Anyone who says there is “no risk” with vaccines is a liar, else why would all throughout history there have been huge billion-dollar payouts for vaccine deaths and injuries? That being said, most vaccines are essential for health but with these covid vaccines there has been a suspension of scepticism and government and corporate coercion that is extremely alarming.

        • Otrebor

          Honestly i think you have a bigger problem to worry about then the vaccine Bailey

    • anti-mario

      To all those wondering if the MRNA vaccine produces the spike.

      1. the vaccine has an imprint (kind of like a foot print but not the foot) of the spike and an enzyme which your immune system’s beta cells identify as an antigen it needs to examine.

      2. your beta cells then process and read the enzyme with the mrna of the spike to watch out for the foot that will cause all this damage.

      Unless the MRNA vaccine gets into one of your cells exactly while its splitting, past the cell wall, past the cell nucleus, guide its self into the exact spot it can attach its self to your cell’s own RNA (when dividing)… its not going to cause any harm to your body. Even if breaks from the enzymes which tell your immune system not to get rid of the useless mrna the body will most likely just get rid of the mrna.

      Your beta cells in your immune system know better than to copy random mrna in the body. If the mrna wiggles free from the enzyme that stabilizes the mrna vaccine, the immune system will just eradicate the mrna anyways.

      You retards fell asleep in biology 101 of high school and it shows. You dumb asses also watched too much resident evil and think thats actual science and it shows.

      I hope in the future humanity will be a little smarter but seeing how the future is based off you, we are F-ed.

    • Pierre Little

      Cellular biology 101. Can not happen as this paper suggests. Spikes created inside cells from mRNA are degraded before they exit the cell through the MCH mechanism and the result it the standard immune system hand off is made to fully consume and degrade these protein peptides. Watch this

  • eah

    Is the ‘spike’ protein that allegedly attacks the vascular system the same one that the Pfizer mRNA vaccine stimulates the body to produce? — asking for a concerned friend who took the vaccine.

    • Jonathan M

      The vaccine has a limited number of spike proteins, and since it’s not part of a virus it cannot reproduce. The vaccine allows the body to recognize spike proteins so it can learn to fight them, without the risk of a virus that can replicate spike proteins to the point of killing a person.

      This explains why the vaccine can make you a little bit ill. If it’s comforting, a little back-of-the-envelope math shows that people are at least 50,000 times more likely to die from covid than to get a serious complication from the vaccine.

      • Star Bait

        How can you give the odds of someone dying of covid vs a vaccine like AstraZenica when you don’t even know their medical history or current medications?

    • SinaSinasina

      Even if it’s turns out to be true that mRna spike proteins can harm your cells. (a pretty tall order) There is not enough of the viral matter in the vaccine to do significant harm without replication, which it cannot do.

  • John Malcolm

    These findings should be VERY WIDELY reported to help vaccine skeptics understand the risks they are taking with their own health and that of others.

    • Star Bailey

      I would argue the opposite. If spike proteins are dangerous, why do the vaccines produce them?

  • Star Bailey

    Don’t the mRNA vaccines produce spike proteins?

    • Jonathan M

      Yes, and that’s why it can make you a little ill. But since it’s not part of a virus, it cannot replicate. This gives your body the opportunity to learn how to fight it without the risk of the virus replicating so much that it does serious damage or kills you.

      • Star Bailey

        Covid makes most people “not ill at all” or “a little ill” as well. The point of the mRNA vaccines that you don’t *need* the virus itself there to replicate because the mRNA is there to be read and the spike protein is produced. The point of the article is that the spike protein is dangerous, so if the vaccine is producing spike proteins, it’s quite a leap in logic to say that the vaccine is “safe” (whatever definition that is today).

    • Pierre Little

      Watch this video. mRNA created Spike proteins CAN NOT free float around and infect other AC2 receptors in your body.

    • CitizenOnce

      Yes, that’s why they induce vascular effects in some cases. Just like the virus.

  • DER

    I agree that if the mRNA vaccines themselves stimulate the human body’s cells to produce spike proteins, shouldn’t there be some concern that by this process the mRNA vaccines could ultimately cause the same vascular damage?

    • Pierre Little

      With mRNA vaccine technology the spike protein is made inside the cellular machinery, but it goes on to be destroyed once it is made inside the cells and CAN NOT EXIT the Cell intact.

    • CitizenOnce

      You are correct

  • Ed Brss

    Vaccines that trigger spike protein production only affect a very limited number of cells, as the genetic material that these vaccines contain does not auto-replicate in the body. In that way, these few cells are able to produce safe levels of spike protein, which are enough to trigger the intended immune response without any of the damaging effects. In contrast, the virus is able to produce many copies of itself in a very short time before the body can make any attempt to control it. This means that very large amounts of circulating spike proteins are produced, generating the adverse effects that the authors identified in their study. If you have access to any vaccine, please take it, they are all good to protect you and your loved ones.

  • pbar

    The Pfizer/BioNTech and Moderna vaccines carry instructions to produce a variant of the spike protein that has been locked into what’s called a “prefusion-stabilized conformation”.

    Because the vaccine produced spike proteins are locked into this state, they cannot properly bind to the ACE2 receptors in other, healthy cells. This is because the normal spike protein must change its shape in order to achieve “fusion” with the ACE2 receptor.

    So the vaccines should be perfectly safe, even in light of this new information.

    • Star Bailey

      No vaccine is “perfectly safe.” It is a calculated risk. And the vaccines are in emergency use trials until 2023. Why can’t people sue pharmaceutical companies if they have disabling reactions or their family members die from it? If they are so safe, surely companies should have confidence in their products?

  • Pierre Little

    This research goes against all cellular biology. China researchers trying to scare people from getting mRNA vaccines? Saying you can get just as sick with the Spike protein as the Covd-19 virus itself? Wow. Incredibly ignorant. With nRNA vaccine technology the spike protein is made inside the cellular machinery, but it goes on to be destroyed once it is made inside the cells and CAN NOT EXIT the Cell intact. This is cellular biology 101. Spikes proteins can not be floating around after being made and transit to other AC2 receptors elsewhere in the body. Incredible this document is even published.

  • Pierre Little

    This whole website is a fake website, likely created by the 50 cent army at the CCP in China. You can not even find any real person on the board listed in Linkedin. This is demonstrably a propaganda site. Martin Beaulieu, Ph.D. from Laval is not a real person.

    Lying CCP. You will not win with your lies.

    • Pierre Little

      Actually found a real Martin Beaulieu on Linkedin and he is a beer brewmaster now? I stand corrected. This site might not be a propaganda site for the CCP but I find it truly hard to understand how it could post an article on the science of mRNA vaccines with the suggestion that the spike protein of the Covd-19 virus could be as bad as the actual virus given that cellular biology precludes spikes migrating elsewhere in the body.

    • CitizenOnce


  • Adam Mercy

    This is not the first paper to show this, Magro (2020) showed this definitively.
    A synethetic mRNA gene is a great way to make spike proteins and cause damage because lipid nano-particles can travel into the brain – whereas the virus does not.

    Caveat Emptor.

    Adam Mercy
    Mercy School | Scientific Media

  • Pierre Little

    I stand corrected. Actually found a real person with Martin Beaulieu on Linkedin and he lists himself as a PHD but is currently doing beer brewing ?

  • NewsView

    Check out this UK model, which predicts on page 10 #32 that up to 70% of COVID-19 hospitalizations/deaths this fall will be among the twice vaccinated. (An oddly specific characterization given that some COVID-19 vaccinations that do not require a second shot.) See:

    The model anticipates a certain amount of vaccine failure in the 50+ group but then goes on to state on page 18 #56 that the rate of hospitalization/death is NOT evidence that vaccine effectiveness is in doubt but rather a reflection of the fact that a high percentage of people in this age group were fully vaccinated to begin with.

    My first instinct would be to blame any Fall/Winter COVID-19 spike on the fact that vaccine-induced immunity is temporary — with some estimates as little as 6-9 months (the apparent hope, however, is that we can go 12 months between boosters). My second instinct would be to blame any Fall/Winter surge in the UK — and similarly here — on variants. However, the model does not account for variants. Given this, what other explanation can there be apart from a lower rate of vaccine effectiveness than we have been led to believe?

    Indeed, there are those who have looked at the vaccine clinical trial data and made the observation that the rate of COVID-19 cases among the control group was too small relative to the reduction of cases in the vaccinated group to extrapolate a high rate of effectiveness for vaccines.

    What’s more, we have Dr. Fauci and others — President Biden among them too — insisting that the fully vaccinated continue to wear their masks. Dr. Fauci has openly said that it is unknown if vaccines will prevent viral shedding vs. limiting serious illness. (The chief hope, apparently, is to limit hospitalizations/death not necessarily case case counts, many of which may presumably become asymptomatic following vaccination.) Meanwhile, NPR — not exactly a conspiracy website — has also reported that the vaccines may contribute to more variants (hastening so-called immune escape). See:

    Taken together, it looks as if Operation Warp Speed delivered a questionable “vaccine” but to recoup their losses Big Pharma still needs to put the jab into people’s arms even though much more is unknown than known!

  • Felix Steinhardt

    My replay is to

    Pierre Little | May 3, 2021 at 12:13 pm | Reply

    With mRNA vaccine technology the spike protein is made inside the cellular machinery, but it goes on to be destroyed once it is made inside the cells and CAN NOT EXIT the Cell intact.


    pbar | May 3, 2021 at 10:14 am | Reply

    The Pfizer/BioNTech and Moderna vaccines carry instructions to produce a variant of the spike protein that has been locked into what’s called a “prefusion-stabilized conformation”.

    Because the vaccine produced spike proteins are locked into this state, they cannot properly bind to the ACE2 receptors in other, healthy cells. This is because the normal spike protein must change its shape in order to achieve “fusion” with the ACE2 receptor.


    All nice, but the spike proteins are already IN the cells since they are produced there and the study says: […] but this is the first study to show that the damage occurs when CELLS are exposed to the spike protein on its own.

    So the spike proteins don’t need to exit the cells and they don’t need to bind to new cells. They are produced INSIDE cells, right where they want to be. I find this very concerning and I already got my first shot.

    • Pierre Little

      Okay they are in the cell… so what? There are no AC2 receptors inside the cell. This is the issue, why create spikes inside cellular machinery? Because it is stopped once made, because the cell recognizes is as foreign protein and send it off for destruction, and hands it’s smashed parts from the endoplasmic reticulum (ER) to the MCH mechanism which hands it off to the T-Cell immune system for removal. This is how the immune system becomes ramped up against these degraded pieces of proteins. The premise of this study is the Spike proteins are attaching to the epithelial cells that line our circulatory system. These spikes are wild versions that are already in the circulatory system from an active infection because they are attached to the membrane holding the nucleocapsid. The mRNA vaccines builds the protein within the safe environment of the host cell structure from the inside out…spikes are not created outside this environment. Which is totally different from the wild version. More confirmation watch this:

      • Felix Steinhardt

        Thank you Pierre for your explanation! I’m a layman but I think I got it.
        The damage happens when a free spike protein binds to a cell. There is no damage when the spike protein is just inside a cell.

        So it’s like the spike protein is a burglar. If a burgler, theoretically, is born inside your house and cannot get out alive and is killed by the residents, there is no damage and no damage in the future at other houses. The damage happens when a burgler breaks in with a pry bar (spike protein bind to a cell and wants to get in).

  • NewsView

    @ Pierre Little

    What leads you to believe that the spike protein will remain in the cell vs. expressed into the surrounding tissue by which not only antibody response will be built up (a good thing) but also attack by NK cells (another aspect of the immune system) and thus pro-thrombotic, pro-inflammatory aftereffects?

    From what I understand, it’s not entirely clear where vaccine-induced spike proteins will show up because that would require tissue biopsies that were not done in human subjects. But there are clues provided by COVID-19 infection itself — and the implications are disturbing apart from the usual antivaxxer suspects. See:

    The mRNA vaccination process “hijacks” the cell to encode these proteins so we’re not talking a limited number taken up by the vaccine itself after which no more are produced by the body. See:

    If these spike proteins are expressed in endothelial cells, which are found in the vascular system, brain and other organs, the protein can presumably damage that tissue in a way that may not be readily apparent. Regardless, studies have apparently found that the spike protein can cross the blood-brain barrier — which is a giant red flag for the decision to target the spike protein for vaccine development on the assumption that it was a passive (harmless) target. See: and

    In Israel, where vaccination rates are much higher, myocarditis cases are under review for possible association with vaccination. Meanwhile, the Department of Justice is investigating myocarditis (inflammation of the heart) following cases in vaccinated service members. Simply put, there are too many VAERS adverse event reports to pass off all serious aftereffects as coincidence or to dismiss them as “background” rates. For example, J&J isn’t the only vaccine where blood coagulation disorders have occurred. We’re on the receiving end of a very incomplete picture from mainstream media because they don’t want to encourage vaccine hesitancy. See:

    As the old saying goes, where there is smoke there is fire. Does that mean people who are vaccinated face the same health risks as COVID-19 itself? No. Having said that, a more complete answer would depend on the age and health status of the vaccinated individual. In elderly patients who are not already on death’s door, tolerance appears to be quite good (less, even, of flu-like symptoms post vaccination). And since elderly people are at increased risk of COVID-19 complications, it makes more sense for them to be vaccinated than not. But does that hold true for the rest of us?

    My educated guess is this: Now that the vaccines are about to be used in kids as young as 12, I expect a more robust immune response and the presence of a better (faster) metabolism will translate into more immediate reports of adverse events among younger vaccine recipients — the same group (with some exceptions!) who would not be expected to be at high risk from COVID-19 itself. In contrast, middle-aged adults with co-morbid conditions who are vaccinated may be more likely to experience delayed adverse events (on the whole).

    Of course, none of this even begins to account for how vaccines will alter our immune response, for better or for worse, to COVID-19 variants. A study out of Israel implies that prepping the immune system to expect the original COVID-19 may paradoxically put it at a disadvantage when exposed to the South African variant. Here is a quote “the prevalence of the South African strain among vaccinated individuals who were infected despite their inoculation was eight times higher than its prevalence in the unvaccinated infected population”. See:

    The COVID-19 vaccine argument thus far has been one-size-fits all: COVID-19 vaccinations are harmful (antivaxxers) vs. helpful (the majority). In reality, the jury is still out — which is why these are approved for emergency use, not “FDA approved” in the usual (year’s long) tradition.

  • Sietze

    We are slowly getting to the right conclusion. The solution for the problem with Covid19 is Zyesame/Aviptadil. This is an a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP). This is concentrated in the lungs to help you to breath. This helps to stop the cytokine storm in the beginning and repairs your lungs (if not to damaged). See the next video and it becomes all clear.

    Aviptadil is now in internatial research project with Remdesivir, which could help in start of the sickness.

  • Rebecca Jesty

    Reading these comments Jonathan is wrong. The new technology treatments give mRNA to teach your own cells to make the spike proteins. The body then recognises these as foreign and starts to make antibodies.

    With this in mind, your own body making the spike protein cant be a good thing, however long they last for.

  • Vaxy

    It is not true that spike proteins can’t exit cells, because reactions in your cells do not happen immediately. The mrna enters a cell (also in the brain, thanks to the lipid hull). Much mrna will be destroyed fast by enzymes but some will trigger the cell to produce the spike proteins. Other enzymes destroy the spike proteins and parts of it will be presented to the immune system outside the cell. So far, your assumption is true. BUT: Then the immune system will destroy that cell (also some brain cells which will not regenerate). Now, when the cell gets destroyed, all spike proteins which were produced shortly and did not become destroyed yet will float through your tissue and if you are unlucky, enter a blood vessel. I think, adverse effects of the vaccine happen more often if the needle hits near a bigger blood vessel in the muscle. The vaccines are clearly beneficial to elderly people but I would never let my children be vaxxed without long term studies.

  • Victor Banks

    In order to overcome the viruses. It must first be understood by all. Where,when,and how, the virus entered the human biological systems. Who committed such evil ? Why did he or she do it ? Because apparently they don’t believe in GOD AND ANGELS. But Science proves as well as they are proof of INTELLIGENCE EXISTENCE. MAN WAS CREATED BY GREAT INTELLIGENCE. THUS VIRUSES WERE CREATED WITH CERTAIN INTELLIGENCE IN THE PHYSICAL ENVIRONMENT. Somewhere over in China. Or more exactly between Russia,China, and the Eastern Province of Tibet. Lies tall mountains in which hidden within them lies a sea of water. So clean,white,and pure. That if one drink from it ! He becomes clean !!!! And white !!!! Also you become able to look down into the middle of the earth. And look into the heavens and see the sun and all the stars in Heaven. So solving the issues of viruses and other harmful parasites.
    Can be overcome by locating this sea.There is one man who saw this sea. And he thought it was glass laying down on the ground. Until he approached it and looking down saw down into the earth and was alarmed. It was as he saw as if someone sliced all the way to the middle. Anyway after drinking this water.He got a different blood type than anyone on earth. And he can transfuse wiping away this virus. Find him.

  • Victor Banks

    The Garden of Eden was found but no one was,or is able to walk into it. It is a beautiful forest with trees so tall and wide. And it is located upon a plateau. Those who are living in the space station over a year. Had to look down and seen it ! There are animals living in it. But the devil and his seed cannot go into it !!!! :

  • Wyatt Mann iz a fkng ID107

    Hey Wyatt Boy, U.R.A. MORE-ON P.O.S. Da world wood B a better place if you wood go kll yslf