The coronavirus disease (COVID-19) is a novel illness that has spread across the globe in just five months. Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral infection binds to the angiotensin-converting enzyme 2 (ACE2) to enter and invade cells.
Antibodies attacking SARS-CoV-2 virus. Illustration: Kateryna Kon / Shutterstock
Previously, concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose people to severe COVID-19. A team of researchers in Spain has found that RAAS inhibitors do not increase the risk of developing severe COVID-19 that may require hospital admission.
ACE2 and the novel coronavirus
The ACE2 is a protein on the surface of many cell types in the body. The SARS-CoV-2 targets the ACE2 on cells by binding and locking into them. Then, the virus enters and invades the cells, making the ACE2 a cellular doorway or receptor for the virus that causes COVID-19.
In contrast, other studies have proposed the use of angiotensin-receptor blockers as a preventive measure and treatment for the coronavirus infection. These drugs may help reduce lung injury caused by angiotensin II.
RAAS inhibitors are among the most used drugs worldwide. They are specifically taken for diseases such as heart failure, hypertension, heart attack, and kidney complications tied to diabetes. These diseases are also considered comorbidities that may heighten the risk of developing severe COVID-19.
RAAS safe to use
In the study, published in The Lancet, the researchers selected patients who are more than 18 years old with a confirmed diagnosis of COVID-19. The patients were admitted to seven hospitals in Madrid, Spain, from March 1 to March 24, 2020.
The team gathered data on the patients' comorbidities and prescriptions up to the month before the admission date. They studied the link between COVID-19 requiring admission to a hospital and the use of RAAS inhibitors compared with the use of other antihypertensive drugs.
The results of the study show that among 1,139 cases and 11,390 population controls, most of the patients had pre-existing cardiovascular disease and risk factors. Further, the team also found that the current use of RAAS inhibitors is not tied to a heightened risk of COVID-19 requiring hospital admission, including those who were admitted in the intensive care unit.
"Our results do not support the hypothesis that the previous intake of RAAS inhibitors facilitates or increases the severity of COVID-19," the researchers said.
"The lack of an increased risk of COVID-19 requiring admission to hospital associated with RAAS inhibitors (compared with other antihypertensive drugs) was found in both patients with most severe and less severe disease, suggesting that the outpatient use of these drugs neither facilitates nor aggravates the infection," they added.
The researchers concluded that available evidence supports that RAAS inhibitors are safe and should not be discontinued for fear of increased COVID-19 risk.
"The data available, along with the important role of ACE inhibitors and angiotensin-receptor blockers in the management of several cardiovascular diseases, do not support their discontinuation as a preventive measure against COVID-19," the authors wrote in the paper.
In another study published in The New England Journal of Medicine, a team of researchers at the Brigham and Women's Hospital and the Harvard Medical School suggests that withdrawing the use of RAAS inhibitors in COVID-19 patients may be harmful, especially for those who are at high risk.
"Abrupt withdrawal of RAAS inhibitors in high-risk patients, including those who have heart failure or have had a myocardial infarction, may result in clinical instability and adverse health outcomes. Until further data are available, we think that RAAS inhibitors should be continued in patients in otherwise stable conditions who are at risk for, being evaluated for, or with Covid-19," the researchers explained.
The coronavirus disease has rippled across the world, causing the death of more than 328,000 people. The United States remains as the country with the highest number of cases, topping 1.55 million infections and at least 93,000 deaths.
Other countries with high numbers of confirmed cases include Russia with at least 308,000 cases, Brazil with 291,579 cases, the United Kingdom with 249,619 cases, Spain with 232,364 cases, and Italy, with 227,364 cases.
- Abajo, F., Martin, S., Abril, G., Lerma, V., Aguilar, M. et al. (2020). Use of renin-angiotensin–aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study. The Lancet. https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31030-8.pdf
- Vaduganathan, M., Vardeny, O., Michel, T, et al. (2020). Renin-Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. The New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMsr2005760