Statins are used to lower cholesterol levels and are believed to reduce the risk of developing the severe form of COVID-19. It is believed that they do so by removing the cholesterol used by the virus to infect the body. This means that statins could reduce the severity of the infection.
This discovery opens the door to new therapeutic pathways using the CH25H gene, which inhibits the virus’ ability to enter cells.
Although there is currently no vaccine or treatment available to fight SARS-Cov-2 infection, the use of safe drugs that are already on the market is one of the preferred therapeutic approaches of many health authorities around the world in the fight against the COVID-19 epidemic.
While the effectiveness of some treatments, such as the antiviral drug Remdesivir, remains controversial in the scientific community, other classes of drugs have shown encouraging results. This is especially true for statins, cholesterol-lowering drugs that are the subject of a recent publication in the American Journal of Cardiology.
According to the authors from the University of San Diego, statins are associated with a lower risk of developing a severe form of COVID-19 and faster recovery times. The reason: this removal of cholesterol from the cell membranes prevents the coronavirus from entering the cell membranes, according to the results of another study, this time published in The EMBO Journal.
Less Covid-19 complications and faster recovery
To enter lung cells and establish respiratory infections, SARS-Cov-2 uses a molecule called ACE2 which is found on the surface of most human cells.
It is, therefore, necessary to block this door by which the coronavirus reaches the lung cells. Statins, which influence the ACE2 enzyme, could be the answer.
To test the effectiveness of this class of cholesterol-lowering drugs, the researchers retrospectively analyzed the medical records of 170 COVID-19 patients and 5,281 control patients hospitalized at UC San Diego Health between February and June 2020. They collected anonymous data on disease severity, length of hospital stay, outcomes, and use of statins, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) in the 30 days prior to hospitalization.
Of the COVID-19 patients, 27% were taking statins at admission, 21% were taking an ACE inhibitor and 12% were taking an ARBs.
The researchers then found that having taken statins before COVID-19 hospitalization reduced the risk of developing a serious form of the disease by 50%. Patients who received statins also recovered faster than patients who did not take cholesterol-lowering medications.
“We have found that statins are not only safe but also potentially protective against a serious infection of COVID-19,” said Professor Lori Daniels, Director of the Cardiovascular Intensive Care Department at UC San Diego Health. Statins, through their known anti-inflammatory effects and binding capabilities, can specifically inhibit SARS-Cov-2 infection, as this could potentially stop the progression of the virus.
The key role of the CH25H gene
How can this protective effect of statins against coronavirus infections be explained? Another study conducted by Professor Tariq Rana, head of the Department of Genetics at the Division of Pediatrics, University of San Diego School of Medicine, examined the effect of statins on a gene called CH25H, which encodes an enzyme that alters cholesterol levels. “I was excited because with HIV, Zika and some others we knew that CH25H blocks the virus’ ability to enter human cells,” the researcher said.
By testing the enzyme activity of the CH25H gene, the research team found that it produces another enzyme called ACAT, which breaks down cholesterol in the cell membrane. They exposed SARS-Cov-2 to the CH25H gene, which then inhibited the virus’s ability to enter cells, almost completely blocking infection. “The difference between untreated cells and cells treated with CH25H was like day and night,” said Dr. Rana.
While SARS-Cov-2 uses the ACE2 receptor to initially bind to a cell, Rana’s study suggests that the virus also needs cholesterol (usually present in cell membranes) to fuse with the cell and enter it. CH25H removes much of the cholesterol from this membrane, thus preventing the virus from entering the cell.
Similarly, statins are likely to be beneficial in preventing or reducing the severity of SARS-CoV-2 infection, since they remove cholesterol from blood vessels but also from cell membranes. As a result, the coronavirus cannot enter them.
Researchers now want to develop the CH25H gene as a therapy. According to them, it may prove to be an even more effective antiviral agent than statins because it specifically targets cholesterol in the cell membranes instead of cholesterol throughout the body. In addition, statins can cause negative side effects such as digestive problems and muscle pain and may not be an option for many people with COVID-19.