Discovery of antibodies to COVID-19 may explain long COVID
Discovery of antibodies to COVID-19 may explain long COVID

Discovery of antibodies to COVID-19 may explain long COVID

UVA Health researchers have discovered a potential explanation for some of the most perplexing mysteries of COVID-19 and the long run of COVID. The surprising findings could lead to new treatments for the difficult acute effects of COVID-19, long-term COVID, and possibly other viruses.

Researchers led by UVA’s Steven L. Zeichner, MD, PhD, discovered that COVID-19 can prompt some people’s bodies to produce antibodies that act like enzymes the body naturally uses to regulate important functions — blood pressure , for example. Related enzymes also regulate other important body functions, such as blood clotting and inflammation.

Doctors may be able to target these “abzymes” to stop their unwanted effects. If abzymes with rogue activities are also responsible for some of the features of long COVID, doctors could target abzymes to treat the difficult and sometimes mysterious symptoms of COVID-19 and long COVID at the source, rather than simply treating downstream symptoms.

“Some patients with COVID-19 have severe symptoms and it is difficult for us to understand their cause. We also have a poor understanding of what causes long-term COVID,” said Zeichner, a pediatric infectious disease expert at UVA Children’s. “Antibodies that act like enzymes are called ‘abzymes.’ Abzymes are not exact copies of enzymes and therefore work differently, sometimes in ways that the original enzyme does not. If patients with COVID-19 produce abzymes, it is possible that these false abzymes could harm many different aspects of physiology. If this turns out to be true, then developing treatments to deplete or block rogue absims may be the most effective way to treat the complications of COVID-19.

Understanding the magnitude of COVID-19

SARS-CoV-2, the virus that causes COVID, has a protein on its surface called the Spike protein. When the virus begins to infect a cell, the Spike protein binds to a protein called angiotensin-converting enzyme 2, or ACE2, on the surface of the cell. ACE2’s normal function in the body is to help regulate blood pressure; it cuts a protein called angiotensin II to make a derivative protein called angiotensin 1-7. Angiotensin II constricts blood vessels, raising blood pressure, while angiotensin 1-7 relaxes blood vessels, lowering blood pressure.

Zeichner and his team thought that some patients could make antibodies against the Spike protein that looked enough like ACE2 that the antibodies also had enzymatic activity like ACE2, and that’s exactly what they found.

Recently, other groups have found that some patients with long-term COVID have problems with their clotting systems and with another system called “complement.” Both the coagulation system and the complement system are controlled by enzymes in the body that cut other proteins to activate them. If patients with prolonged COVID produce abzymes that activate proteins that control processes such as coagulation and inflammation, this may explain the source of some of the long symptoms of COVID and why the long symptoms of COVID persist even after the body has cleared the initial infection. This may also explain the rare side effects of the COVID-19 vaccination.

To determine whether the antibodies could have unexpected effects in patients with COVID, Zeichner and his colleagues examined plasma samples collected from 67 volunteers with moderate or severe COVID on or around day 7 of their hospitalization. The researchers compared what they found with plasma collected in 2018, before the pandemic began. The results show that a minority of COVID patients have antibodies that act like enzymes.

Although our understanding of the potential role of abzymes in COVID-19 is still in its early stages, enzyme antibodies have already been detected in certain cases of HIV, Ziechner notes. This means there is a precedent for a virus to trigger abzyme formation. It also suggests that other viruses can cause similar effects.

Zeichner, who is developing a universal coronavirus vaccine, expects UVA’s new findings to renew interest in abzymes in medical research. He also hopes his discovery will lead to better treatments for patients with both acute COVID-19 and long-term COVID.

“Now we need to study pure versions of antibodies with enzyme activity to see how the abzymes might work in more detail, and we need to study patients who have had COVID-19 who did and did not develop long-term COVID,” he said. “There is still much work to be done, but I think we have made a good start in developing a new understanding of this challenging disease that has caused so much suffering and death around the world.” The first step to developing effective new therapies for a disease is developing a good understanding of the underlying causes of the disease, and we have taken that first step.

The findings have been published

The researchers published their findings in the scientific journal mBio, a publication of the American Society for Microbiology. The research team consisted of Yufeng Song, Regan Myers, Frances Mel, Lila Murphy, Bailey Brooks and faculty members from the Department of Medicine, Jeffrey M. Wilson, Alexandra Kadl, Judith Woodfolk.

“It is great to have such talented and dedicated colleagues here at UVA who are excited to work on new and unconventional research projects,” said Zeichner.

Zeichner is the McClemore Birdsong Professor in the Departments of Pediatrics and Microbiology, Immunology and Cancer Biology at the University of Virginia; the director of the Pendleton Pediatric Infectious Diseases Laboratory; and part of the UVA Child Health Research Center.

Abzym’s research was supported by UVA, including the Manning Fund for COVID-19 Research at UVA; the Ivy Foundation; Pendleton Laboratory Fund for Research in Pediatric Infectious Diseases; a Minerva Research Grant from the College Board; Coulter Foundation; and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, grant R01 AI176515. Additional support came from the HHV-6 Foundation.

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