Controversial Study Links COVID-19 Severity to ACEIs and ARBs, Despite Warning of No 'Sound Scientific Basis or Evidence'

A controversial study suggesting COVID-19 may be more severe in some people because of the medications they take should not stop taking their drugs, organizations have warned. U.S. scientist James H. Diaz has published a manuscript that links enzyme inhibitors and angiotensin receptor blockers to the virus, suggesting they help the SARS-CoV-2 virus bind to the lower respiratory tracts of a person infected.

The hypothesis has been heavily criticized by a hypertension and cardiology organization, which says there is no scientific evidence to support it. Diaz also does not suggest people stop taking their medications, but has said more research should be carried out to establish whether his proposed link is viable.

Previous research on coronavirus patients has indicated people are at greater risk of severe health effects from COVID-19, the disease caused by the virus, if they are suffering from certain conditions. These include diabetes, heart disease and high blood pressure. One Chinese scientist working in Wuhan, where the outbreak is believed to have started, found that of 170 patients who died from the new coronavirus, half were suffering from hypertension—a condition that increases the risk of heart attack and stroke.

Another study published in JAMA also found people with high blood pressure, cardiovascular disease and diabetes experienced worse outcomes. The case fatality rate was 10.5 percent higher for people with cardiovascular disease, 7.3 percent for diabetes, 6.3 percent for chronic respiratory disease and 6 percent for hypertension.

"Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are highly recommended medications for patients with cardiovascular diseases including heart attacks, high blood pressure, diabetes and chronic kidney disease to name a few," Diaz said in a statement. "Many of those who develop these diseases are older adults. They are prescribed these medications and take them every day."

In a letter accepted for publication in the Journal of Travel Medicine, Diaz looks at the way SARS beta coronaviruses, which includes SARS-CoV-2, bind to receptors in the lower respiratory, specifically the angiotensin converting enzyme 2 (ACE2). This is an enzyme attached to the surface of cells in the lungs, heart, kidneys, intestines and arteries.

Models have previously suggested ACE inhibitors may increase the number of ACE2 receptors in the cardiopulmonary circulation, meaning people who take ACEIS and ARBs may have more of these receptors in their lungs that SARS-CoV-2 can bind to. Diaz says this may make them at greater risk of severe infection.

Before his paper appeared online, the European Society of Cardiology (ESC) of the Council on Hypertension issued a statement waning people not to stop taking their medication, saying there is no "sound scientific basis or evidence to support it."

It said: "Because of the social media-related amplification, patients taking these drugs for their high blood pressure and their doctors have become increasingly concerned, and, in some cases, have stopped taking their ACE-I or ARB medications.

"This speculation about the safety of ACE-i or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it. Indeed, there is evidence from studies in animals suggesting that these medications might be rather protective against serious lung complications in patients with COVID-19 infection, but to date there is no data in humans.

"The wish to highlight the lack of any evidence supporting harmful effect of ACE-I and ARB in the context of the pandemic COVID-19 outbreak.

"The Council on Hypertension strongly recommend that physicians and patients should continue treatment with their usual anti-hypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEi or ARBs should be discontinued because of the COVID-19 infection."

Representative image of a coronavirus. A study has linked drugs taken for hypertension and other conditions to the severity of COVID-19. iStock

Bryan Williams, Past-Chairman of the ESC Council on Hypertension, told Newsweek he read Diaz's paper "with concern." He said the medications in question are some of the widely used in the world and there is no basis for the claims put forward. "In fact, there is more evidence from high quality scientific studies in animal models of coronavirus diseases that blockade of the renin angiotensin system with these drugs was beneficial in reducing lung injury following coronavirus infection," he said. "Moreover, treatments are being tested that are designed to deliver ACE2 to the lung in an endeavour to protect the lungs in people with severe infection."

He said the association highlighted is "simply a function of age," with older people more likely to have hypertension, cardiovascular disease, diabetes and so on. "It has nothing to do with whether they are treated with ACE-inhibitors or ARBs and the consensus view of experts in this field, many of whom also take these drugs, and will continue to take them after reviewing the data, is that these are ill founded concerns due to flawed analysis of the epidemiological data. There is absolutely no evidence that ACE-inhibitors or ARBs increase the risk of COVID-19 infection or severe consequences from it. On the contrary, the evidence suggests if anything, the opposite may be true... The tragedy is that the hysteria fuelled by social media and these kinds of articles could lead to many people discontinuing these drugs which could result in as much harm as the virus itself."

COVID-19 is believed to be asymptomatic in most people who get it. For people who do show symptoms, it presents as a fever and cough. In most cases, these symptoms are mild or moderate. But in some cases, mostly among older people, the virus results in severe symptoms and death. Current figures from Johns Hopkins University show there have been almost 384,000 confirmed cases of COVID-19, with over 16,500 deaths. More than 100,000 have recovered from the virus.

Diaz says more research is needed to investigate the potential link between COVID-19 and ACEIs or ARBs. "Patients treated with ACEIs and ARBs for cardiovascular diseases should not stop taking their medicine," he said.

World Health Organization advice for avoiding spread of coronavirus disease (COVID-19)

Hygiene advice

  • Clean hands frequently with soap and water, or alcohol-based hand rub.
  • Wash hands after coughing or sneezing; when caring for the sick; before, during and after food preparation; before eating; after using the toilet; when hands are visibly dirty; and after handling animals or waste.
  • Maintain at least 1 meter (3 feet) distance from anyone who is coughing or sneezing.
  • Avoid touching your hands, nose and mouth. Do not spit in public.
  • Cover your mouth and nose with a tissue or bent elbow when coughing or sneezing. Discard the tissue immediately and clean your hands.

Medical advice

  • If you feel unwell (fever, cough, difficulty breathing) seek medical care early and call local health authorities in advance.
  • Stay up to date on COVID-19 developments issued by health authorities and follow their guidance.

Mask usage

  • Healthy individuals only need to wear a mask if taking care of a sick person.
  • Wear a mask if you are coughing or sneezing.
  • Masks are effective when used in combination with frequent hand cleaning.
  • Do not touch the mask while wearing it. Clean hands if you touch the mask.
  • Learn how to properly put on, remove and dispose of masks. Clean hands after disposing of mask.
  • Do not reuse single-use masks.

This story has been updated to include quotes from Bryan Williams.

Correction, 3/24/2020, 12:05 p.m.: The name of the Council on Hypertension of the European Society of Cardiology has been corrected.