Scientists Found Cause of Unusual Pathologies After COVID-19 Recovery

American biologists have discovered the cause of a wide range of symptoms that can persist long after formal recovery from COVID-19. The reason is that the virus disrupts the normal function of the ACE2 receptor, which is involved in many of the protein bindings necessary for normal body function. The results are published in the journal PeerJ – Life& Environment.

Many people who have had COVID-19 continue to suffer for weeks, and sometimes months, even after testing negative for the coronavirus from long-term symptoms of post-CVID syndrome, such as abnormal blood clotting, heart failure, kidney damage, confusion, memory loss or difficulty concentrating, gastrointestinal problems and even male infertility.

Although the SARS-CoV2 virus itself has been fairly well studied to date, the mechanisms that cause these unusual complications, which are not directly related to the virus, have remained unclear until now. Researchers at the University of Rochester have suggested that the cause of numerous organ failures after COVID-19 is a disruption of protein connections.

The SARS-CoV2 coronavirus is known to use the ACE2 receptor, angiotensin-converting enzyme 2, to enter human cells. Using an evolution rate correlation approach that they developed, the scientists identified protein partners of ACE2. The researchers assumed that ACE2 is most likely to have functional interactions with those proteins that have the same rate of change with it during evolution.

“We hypothesize that ACE2 has protein interactions that are disrupted during SARS-CoV-2 infection, which contributes to the spectrum of COVID-19 pathologies,” University of Rochester biology professor John Werren, the study leader, is quoted in a press release.

The evolution rate correlation method allowed the authors to identify a number of potential partner proteins for ACE2 that had not previously been identified as interacting with ACE2, but which may be directly related to complications faced by people infected with the coronavirus – excessive blood clotting as well as an overactive inflammatory response known as a cytokine storm.

The researchers found a link between ACE2 and key proteins involved in the coagulation pathway. According to the authors, this link may underlie impaired blood clotting throughout the body, one of the hallmarks of severe COVID-19. Some proteins involved in cytokine signaling also appear to evolve with ACE2.

“These candidate protein interactions have yet to be confirmed. But if they are confirmed, our results will help develop more effective treatments for COVID-19 and chronic complications following it,” says Werren.

Biomedical researchers now use a number of powerful tools to detect and examine proteins that interact with each other in biological processes. These include genetic screening, protein co-precipitation and proteomic profiling. The authors hope that the protein evolution rate correlation method they developed will be a useful addition to the biomedical research toolkit.