Why Is COVID-19 Severe for Some?

Are the antibodies we produce to fight COVID-19 infection causing severe disease? A new paper—so new in fact that it hasn’t yet been peer-reviewed—from scientists in Hangzhou, China, appears to indicate just that. The researchers’ data suggests that at least two antibodies that target the spike protein that enables the COVID-19 virus to enter human cells are “pathogenic”—meaning these antibodies create illness all by themselves. It’s hard to think of antibodies—one of the body’s best infection fighters—as “pathogenic,” but that’s exactly what happens in autoimmune disease. Antibodies that the body develops in response to foreign invaders attach to body tissues instead, sometimes causing catastrophic damage. In early 2020, Japanese researchers discovered that many COVID-19 deaths were caused by part of the body’s immune reaction. In a peer-reviewed article published in Inflammation and Regeneration, the scientists argued that it was a “cytokine storm” that overwhelmed the body and was implicated in the high death rates from the virus. This new Chinese study shows that yet another component of the immune system may be a danger as well. The fact that antibodies that target COVID-19’s spike protein are harmful is disturbing enough, but it’s especially disturbing knowing that these same antibodies are likely to be triggered by COVID-19 vaccines as well as the virus. All three of the vaccines approved for emergency use by the CDC stimulate the production of antibodies against the spike protein—the mRNA vaccines from Moderna and Pfizer, and the recombinant vector vaccine from Johnson and Johnson. Spike Protein Antibodies Attack Body Tissues The Chinese researchers suspected that some antibodies triggered by a pathogenic virus could attack body tissues. To test the hypothesis, they identified seven different COVID-19 antibodies. They then analyzed how well each of these antibodies bound to human lung cells, both healthy and damaged ones. Antibodies binding to your own tissue cells can cause autoimmune damage. As the researchers expected, two of the antibodies bound strongly to damaged lung cells—and one of those bound strongly to healthy cells as well. The researchers then injected the antibodies, as well as some combinations, into the bodies of healthy pregnant mice at three-day intervals. They wanted to see what, if any, damage the antibodies would do to the mice and their pups. Again as expected, the same two antibodies that had bound well to the human lung cells did extensive damage to the mouse pups’ tissues. In fact, the antibody that could bind to healthy human lung cells, REGN10987, killed nearly half the pups. “This is a very troubling finding,” says Zoey O’Toole, a vaccine safety advocate who has a background in physics and engineering and who reviewed the study carefully. “It should give anyone pause, especially pregnant women.” How Does SARS-CoV-2 Kill? One of the big questions about SARS-CoV-2, also known as COVID-19, is exactly how it causes serious illness in those who have died as well as in others who develop long-term symptoms. Most viruses cause short-term illness that resolves once the body has had time to develop antibodies, which appears to be the case for the majority of people who contract COVID-19. Why is it, then, that some people die after two to three weeks of illness, when their immune systems have already cleared the virus from their bodies? And why do some people—known as “long haulers”—have long-term multi-organ damage that seems to have nothing to do with the virus itself? We know that no two people have identical immune responses. With COVID-19, we’ve also seen that those who get severely ill have higher levels of inflammatory cytokines in their blood. This is the “cytokine storm” that the media latched onto as an explanation for severe infectious disease. How Antibodies Create Severe Disease But elevated cytokines are only part of the picture. Researchers have long suspected an autoimmune aspect to severe COVID-19 disease as well. An article in Nature in January noted that surprisingly high percentages of people with severe disease from COVID-19 had auto-immune antibodies. These antibodies targeted the immune system itself, as well as the blood vessels, heart, and brain. Since COVID-19 was first identified, we have seen auto-immune responses worsening the effect of the disease, increasing inflammation and immune dysregulation, and sometimes increasing the activity of the virus itself. The Chinese researchers don’t suggest how the antibodies damage tissues, but autoimmunity researchers have long understood that the particular proteins our antibodies lock on to when they target a virus are sometimes found in our own cells. This “molecular mimicry” might be only a partial match, but even that can be enough to cause otherwise helpful antibodies to attack our own healthy cells. COVID-19 Vaccine Design The findings from this pre-print have profound implications for vaccine design. In or

Why Is COVID-19 Severe for Some?

Are the antibodies we produce to fight COVID-19 infection causing severe disease?

A new paper—so new in fact that it hasn’t yet been peer-reviewed—from scientists in Hangzhou, China, appears to indicate just that.

The researchers’ data suggests that at least two antibodies that target the spike protein that enables the COVID-19 virus to enter human cells are “pathogenic”—meaning these antibodies create illness all by themselves.

It’s hard to think of antibodies—one of the body’s best infection fighters—as “pathogenic,” but that’s exactly what happens in autoimmune disease. Antibodies that the body develops in response to foreign invaders attach to body tissues instead, sometimes causing catastrophic damage.

In early 2020, Japanese researchers discovered that many COVID-19 deaths were caused by part of the body’s immune reaction. In a peer-reviewed article published in Inflammation and Regeneration, the scientists argued that it was a “cytokine storm” that overwhelmed the body and was implicated in the high death rates from the virus.

This new Chinese study shows that yet another component of the immune system may be a danger as well.

The fact that antibodies that target COVID-19’s spike protein are harmful is disturbing enough, but it’s especially disturbing knowing that these same antibodies are likely to be triggered by COVID-19 vaccines as well as the virus.

All three of the vaccines approved for emergency use by the CDC stimulate the production of antibodies against the spike protein—the mRNA vaccines from Moderna and Pfizer, and the recombinant vector vaccine from Johnson and Johnson.

Spike Protein Antibodies Attack Body Tissues

The Chinese researchers suspected that some antibodies triggered by a pathogenic virus could attack body tissues. To test the hypothesis, they identified seven different COVID-19 antibodies. They then analyzed how well each of these antibodies bound to human lung cells, both healthy and damaged ones. Antibodies binding to your own tissue cells can cause autoimmune damage.

As the researchers expected, two of the antibodies bound strongly to damaged lung cells—and one of those bound strongly to healthy cells as well.

The researchers then injected the antibodies, as well as some combinations, into the bodies of healthy pregnant mice at three-day intervals. They wanted to see what, if any, damage the antibodies would do to the mice and their pups.

Again as expected, the same two antibodies that had bound well to the human lung cells did extensive damage to the mouse pups’ tissues.

In fact, the antibody that could bind to healthy human lung cells, REGN10987, killed nearly half the pups.

“This is a very troubling finding,” says Zoey O’Toole, a vaccine safety advocate who has a background in physics and engineering and who reviewed the study carefully. “It should give anyone pause, especially pregnant women.”

How Does SARS-CoV-2 Kill?

One of the big questions about SARS-CoV-2, also known as COVID-19, is exactly how it causes serious illness in those who have died as well as in others who develop long-term symptoms.

Most viruses cause short-term illness that resolves once the body has had time to develop antibodies, which appears to be the case for the majority of people who contract COVID-19.

Why is it, then, that some people die after two to three weeks of illness, when their immune systems have already cleared the virus from their bodies?

And why do some people—known as “long haulers”—have long-term multi-organ damage that seems to have nothing to do with the virus itself?

We know that no two people have identical immune responses. With COVID-19, we’ve also seen that those who get severely ill have higher levels of inflammatory cytokines in their blood. This is the “cytokine storm” that the media latched onto as an explanation for severe infectious disease.

How Antibodies Create Severe Disease

But elevated cytokines are only part of the picture. Researchers have long suspected an autoimmune aspect to severe COVID-19 disease as well.

An article in Nature in January noted that surprisingly high percentages of people with severe disease from COVID-19 had auto-immune antibodies. These antibodies targeted the immune system itself, as well as the blood vessels, heart, and brain.

Since COVID-19 was first identified, we have seen auto-immune responses worsening the effect of the disease, increasing inflammation and immune dysregulation, and sometimes increasing the activity of the virus itself.

The Chinese researchers don’t suggest how the antibodies damage tissues, but autoimmunity researchers have long understood that the particular proteins our antibodies lock on to when they target a virus are sometimes found in our own cells.

This “molecular mimicry” might be only a partial match, but even that can be enough to cause otherwise helpful antibodies to attack our own healthy cells.

COVID-19 Vaccine Design

The findings from this pre-print have profound implications for vaccine design. In order for a vaccine to be as safe and effective as possible, it would have to be one that stimulates antibodies that neutralize the pathogen but don’t bind to any body tissues, so that people who got it would be safe from autoimmune effects.

Unfortunately, it seems that industry scientists didn’t take molecular mimicry into consideration when designing the COVID-19 vaccines.

The spike protein that makes SARS-CoV-2 so infectious to humans was the target the vaccine makers focused on when designing their vaccines. They believed that the spike protein itself, apart from the rest of the virus, was harmless. If the isolated protein wasn’t the disease agent, getting the body to make the protein for a short time would be safe.

But, as the new research from China underscores, there may be at least three problems with this approach.

Potential Problems with COVID-19 Spike Protein Vaccines

Firstly, the spike protein itself isn’t harmless, as has since been found. In fact, according to science published by an international team of researchers in March in the journal Circulation Research, the spike protein can damage lung endothelial cells, just like the ones that bound to the antibodies in the Chinese study, as well as the endothelial cells that line blood vessels throughout the body.

“If you remove the replicating capabilities of the virus, it still has a major damaging effect on the vascular cells,” Dr. Uri Manor, co-author of the study and a researcher at the Salk Institute of Biological Studies in La Jolla, California, said in an interview for Salk.edu.

In the first paragraph of the press release, Salk.edu asserts in parentheses that spike proteins “behave very differently from those safely encoded in the vaccines.” However, neither the study itself or the press release offer any evidence to justify this claim. At the same time, we have seen that many adverse effects reported after vaccination, including blood clots and strokes, are vascular events similar to those associated with the disease itself.

Secondly, as this new research shows, antibodies generated to neutralize the spike protein may be particularly toxic to human cells, especially if the cells have already been damaged.

Finally, the Hangzhou researchers’ data suggested that the one thing that could prevent the ill effects of the pathogenic antibodies is when there are also non-pathogenic antibodies alongside them, doing their job normally. But whether the vaccines as they’ve been formulated can actually trigger production of healthy, non-pathogenic antibodies remains an open question.

“This study suggests that antibodies to other parts of the virus can counteract the potential harm of anti-spike antibodies,” explains O’Toole. “That’s an important finding. But there’s no virus in the mRNA vaccines. So, it’s very unlikely that these vaccines can produce enough beneficial antibodies to help.”

The Upshot

As we learn more about SARS-CoV-2’s ability to harm human beings, there is a growing body of evidence that suggests the vaccines can also cause harm.

In our rush to find a way to prevent severe COVID-19, we may unwittingly be doing more harm than good. It may be years before we know the full extent of the damage.

Which was worse, the disease or its preventive? Only time will tell.

Jennifer Margulis

Jennifer Margulis

Jennifer Margulis, Ph.D., is an award-winning journalist and author of Your Baby, Your Way: Taking Charge of Your Pregnancy, Childbirth, and Parenting Decisions for a Happier, Healthier Family. A Fulbright awardee and mother of four, she has worked on a child survival campaign in West Africa, advocated for an end to child slavery in Pakistan on prime-time TV in France, and taught post-colonial literature to non-traditional students in inner-city Atlanta. Learn more about her at JenniferMargulis.net