New Study on Possible Causes of Post-COVID Syndrome

There has been a buzz in the media about some exciting new research that has begun to unravel what may be causing Post-Acute Sequale of SARS-COV2 (PASC). A recent study from the University of Arkansas for Medical Sciences made a discovery about auto-antibodies in PASC. Antibodies are the parts of our body that help fight off infections from things like the coronavirus. When antibodies attack a person’s own cells, it is called an auto-antibody.

Specifically, this study found auto-antibodies against angiotensin converting enzyme 2 (ACE2) in patients with PASC. It is already well known that ACE2 is a very important protein in the body that is responsible for many important functions. Specifically, ACE2 is a protein found on the surface of many cell types and tissues including those found within the lungs, heart, blood vessels, kidneys, liver, and gastrointestinal tract. It helps regulate cell function by decreasing the amount of angiotensin II, another protein that can cause widespread inflammation when left unchecked. Changes in how this enzyme functions could lead to numerous symptoms, such as changes in blood pressure, pain, inflammation, and fatigue.

While it is tempting to believe we have found the answer to PASC, caution and patience are needed. All research, published or unpublished, has its limitations. In this case, researchers had no way of knowing the symptoms of the the blood sample donors since the samples were de-identified. In other words, there was no way to make a connection between auto-antibody levels or ACE2 activity and symptom severity. Likewise, the researchers also did not know when in the donor’s illness the samples were taken. Were they taken on day 1 of the infection or day 30?

Another limitation was the small number of samples analyzed.  A total of 80 blood samples were tested, 67 from patients known to have COVID-19 infection, and 13 without. Typically, having more participants allows researchers to be more confident that their findings are real, and not just occurring by chance. It is kind of like flipping a quarter. If you flip a quarter, it will either end up as heads or tails.  There are no other options. The chance of getting heads or tails is equal (in a perfect world, don’t get me started on how dirty quarters are).  Yet, flip a quarter ten times, you might get 7 heads and 3 tails.  Does that mean something is wrong with your coin? Not at all, that’s just the nature of statistics.  If you flip the coin 10 trillion times, you are going to get pretty close to 50% tails and 50% heads.

Finally, the researchers noted that auto-antibodies were more frequently present in patients who were hospitalized versus outpatients. This is surprising since some studies, including our own at Mayo Clinic, have found that most of our patients with post-COVID symptoms were never hospitalized.  Also, it was noted that the study focused on ACE2 free in the blood, which is not nearly as active as the ACE2 that is bound to the surfaces of cells.

These limitations do not indicate that this exciting research is of low quality or faulty. In fact, this is an excellent study and a good step forward in figuring out this condition. This is one of the first few studies looking at what may be happening on a chemical level in PASC. In addition, in the main text of the article, the authors clearly showed their methods and data, noted the limitations, and mentioned there were no financial conflicts to worry about.  But all research articles need healthy skepticism and scrutiny. Only by looking beyond the sensational headlines and even article abstracts, will we be able to figure out PASC and avoid the pitfalls

Learn more about the most recent developments with post-COVID syndrome by following the Newsfeed and discuss your experience in the Post-COVID Recovery discussion group.