Cholesterol-lowering medications called statins were found to decrease the risk of severe COVID-19. According to a group of researchers, the secret might be the reduction in cholesterol levels that hampered the coronavirus.
The association between statin and less severe COVID-19 was revealed by researchers at the University of California – San Diego (UCSD), a US public research university. They found that patients who were taking statins for high cholesterol had less severe COVID-19 symptoms. Their investigation showed that a cellular mechanism might be disruptive for SARS-CoV-2's ability to infect healthy cells. The less cholesterol there was inside cells, the less the chance the coronavirus could infect. They published their findings in the American Journal of Cardiology and in The EMBO Journal.
Cardiovascular Deaths and Risk Factors
The American Heart Association, a US-based non-profit organization, defines cardiovascular diseases as an umbrella term for conditions related to heart problems and stroke. The term encompasses health issues in the heart, blood vessels, and blood vessels in the brain. Heart disease often refers to the accumulation of plaque inside arteries, while arrhythmia refers to the abnormal rhythm of the heart. Any of these problems can induce major complications to the cardiovascular and nervous systems.
In 2016, high systolic blood pressure was the top risk factor worldwide in cardiovascular disease, as per the German portal for statistics Statista. It was followed by dietary risks at 51.5%, high total cholesterol at 24.9%, air pollution at 18.9%, tobacco at 16.5%, high body mass index at 16.2%, high blood sugar at 16.1%, impaired kidney function at 7.8%, low physical activity at 7.4%, alcohol use at 4.5%, lead exposure at 2.9%, and occupational carcinogens at 1.5%.
Meanwhile, the online resource of research data Our World in Data highlighted the estimated number of deaths due to cardiovascular diseases in 2017. An estimated 17.79 million deaths were accounted for cardiovascular diseases worldwide. That was higher than the 17.52 million annual deaths in the past year. By age group, the estimated deaths were 11.34 million among adults aged 70 years and older, 5.15 million among adults aged 50 to 69 years, 1.26 million among people aged 15 to 49 years, 15,630 among children five to 14 years, and 30,091 among children younger than five years.
While many cardiovascular diseases are incurable, there are several ways to manage them. Oftentimes, doctors prescribed medications to control blood cholesterol, high blood pressure, and blood sugar levels to reduce the risk of health complications. If paired with proper diet and physical exercise, a patient may live a quality life. One of the drugs doctors prescribe is statin to control blood cholesterol.
Statin Decreases Severity of COVID-19
Recently, researchers at UCSD found a correlation between statin and COVID-19 severity. Initially, statin was observed to reduce the severity of the novel disease. But there was no obvious reason that could explain how the drug does it. Statin could only lower blood cholesterol and could not influence the infectivity of SARS-CoV-2. The truth was later revealed and statin did show a connection to COVID-19. The connection was cholesterol present within cells.
"We needed to confirm whether or not the use of statins has an impact on a person's severity of SARS-CoV-2 infection and determine if it was safe for our patients to continue with their medications," said Dr. Lori Daniels, the lead author of the clinical part of the study and director of the Cardiovascular Intensive Care Unit at UCSD Health.
Studies in the structure and composition of SARS-CoV-2 showed how it infects healthy cells. The virus requires the ACE2 receptor to hijack and control cellular machinery. This receptor is located on the outer surfaces of numerous human cells. The receptor plays a role in regulating blood pressure. As such, it can be affected by statin and similar medications for cardiovascular diseases. Yet the virus prefers to attack cells in the lungs.
Then, there is a problem in COVID-19 patients with cardiovascular diseases. Some doctors recommend discontinuation of maintenance medications, while others do not. The issue is some doctors think that those medications may adversely influence COVID-19 patients. But recent studies showed that stopping maintenance drugs may increase the risk of COVID-19 mortality.
Dr. Daniels and colleagues decided to examine if statins and other similar medications could adversely affect COVID-19 patients. They performed a retrospective analysis of electronic medical records of 170 COVID-19 patients and 5,281 non-COVID-19 patients hospitalized at UCSD Health, between February and June 2020. The data they collected was anonymized but included useful information, such as disease severity, length of hospitalization, outcome, and use of cardiovascular medications. The medications they highlighted were statins, ACE inhibitors, and ARBs. They measured the use of any of those drugs 30 days before hospitalization.
Results showed that 27% of patients were on statins, 21% were on ACE inhibitors, and 12% were on ARBs. The average hospitalization length among subjects was 9.7 days. Among the three cardiovascular drugs, statin had the highest statistical association with decreased COVID-19 severity of more than 50%. Patients who used statin before admission had a higher recovery rate than patients who did not use the drug.
Researchers suggested that statin features a protective effect against SARS-CoV-2. The possible explanation is the anti-inflammatory effects of the drug and binding capabilities, which hindered the infectivity of the coronavirus. Yet the explanation does not specify the molecular processes involved.
Tariq Rana, chief of the Division of Genetics at UCSD School of Medicine, led The EMBO study. Six months before Rana and his team got wind of statin, they were looking into genes that would turn on in lung cells as a response to the coronavirus. They identified the CH25H gene that was responding to the pathogen. The gene was also linked to an enzyme, which modifies cholesterol. Rana basically determined the molecular processes associated with statin use.
Inside the cells, the enzymatic activity of the gene produces a modified form of cholesterol called 25-hydroxycholesterol or 25HC. That cholesterol activates an enzyme known as ACAT located in the endoplasmic reticulum of cells. ACAT depletes accessible cholesterol on the cell membrane. Although SARS-CoV-2 would need the ACE2 receptor, it could not complete the hijack without cholesterol. Statin and similar drugs could remove cholesterol from cell membranes, the same way they do on blood vessels. It practically prevented the coronavirus from getting inside healthy cells.
Researchers speculated that if a drug based on the findings can be done, it may work as an antiviral for COVID-19. Such a drug will target the cholesterol in cell membranes instead of the cholesterol in blood vessels. This limits the potential side effects notable on statins.