The global search for answers to long COVID-19 yielded a possible cause in 2021 by a research team in the UAMS Division of Nephrology. Their discovery of rogue antibodies that appear to be key players in long COVID-19 was published in The Public Library of Science ONE (PLOS ONE), drawing national attention and hope for those with the syndrome. Long COVID-19’s symptoms include fatigue, brain fog, difficulty breathing and joint pain, which disrupt educations, careers and the basic activities of life.
Leading the UAMS research is John Arthur, M.D., Ph.D., a nephrologist who has treated kidney failures caused by the virus, SARS-CoV-2. He became aware that a protein known as ACE2 (angiotensin-converting enzyme 2) plays a key role in the body’s immune response to coronavirus. Arthur has studied ACE2 for many years because of its role in kidney function. “ACE2 just so happens to be the protein that the coronavirus hijacks to get into cells,” said Arthur. Arthur is the chief of nephrology at UAMS, and Co-Director of the UAMS Translational Research Institute.
His research in 2020 of ACE2’s role in coronavirus infections and then a 2021 conversation with Terry Harville, M.D., Ph.D., led to the discovery of rogue antibodies that appear weeks after an initial COVID-19 infection. Harville is a professor in the Department of Pathology and Department of Internal Medicine, and medical director of the Tissue Typing Lab at UAMS.
The two hypothesized that in people with long COVID, the antibodies created to attack the virus lead to autoantibodies that attack the ACE2. The autoantibodies attach to the ACE2 and disrupt its work, a possible cause of long COVID-19.
The team tested de-identified blood samples for ACE2 antibodies in 67 patients with known SARS-CoV-2 infection and 13 with no history of infection. In 81% of patients with a history of COVID-19, the samples had the autoantibodies that attacked the ACE2. In participants with no history of COVID-19, no autoantibodies were created to attack the ACE2 enzyme.
“Everything that we’ve found is consistent with these autoantibodies as the instigators of long COVID, so it’s an exciting development that merits further study,” Arthur said.
What’s Next?
Arthur is moving his research into the next phase to determine whether there is an association between long COVID-19 symptoms and the rogue autoantibodies. In spring 2022, his team was sending surveys to every person tested for COVID-19 in the UAMS system – more than 100,000 people. They are also collecting some 10,000 remnant blood samples.