What data is there for physicians to advise patients taking Ace Inhibitors during the COVID-19 pandemic?

Question

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound aminopeptidase that has a vital role in the cardiovascular and immune systems4. ACE2 is involved in heart function and the development of hypertension and diabetes mellitus. In addition, ACE2 has been identified as a functional receptor for coronaviruses4, including SARS-CoV and SARS-CoV-2. SARS-CoV-2 infection is triggered by binding of the spike protein of the virus to ACE2, which is highly expressed in the heart and lungs4. SARS-CoV-2 mainly invades alveolar epithelial cells, resulting in respiratory symptoms.

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SARS-CoV-2 is thought to infect host cells through ACE2 to cause COVID-19, while also causing damage to the myocardium, although the specific mechanisms are uncertain. Patients with underlying CVD and SARS-CoV-2 infection have an adverse prognosis. Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

Although women have higher levels of ACE2 receptors, those taking ACEI anti-hypertensive drugs have higher levels again as a result of the action of these drugs.

Myocardial injury associated with the SARS-CoV-2 occurred in 5 of the first 41 patients diagnosed with COVID-19 in Wuhan

and there are reports that MERS-CoV also caused cardiac injury.

So, is there other data for physicians to assess on whether they should change their patients' anti-hypertensive medications during this pandemic?

https://www.nature.com/articles/s41569-020-0360-5

Answer 1

The question boils down to does increasing the number of ACE2 receptors increase or lower your risk of severe disease with Covid-19. Increasing the number of receptors might increase the number of attack points for the virus, or, increasing the number of receptors might reduce the risk of lung damage as ACE2 acts to protect the lung. We know that the ACE2 receptor is encoded on the X chromosome and women, who have more ACE2 receptors, do better than men in the mortality statistics.

We now have some observational data to suggest that ARBI help protect the lungs against SARS-CoV-2, approximately 34% less likely to have severe disease (OR=0.343, 95% CI 0.128-0.916, p=0.025). There wasn't enough data to inform about ACEI.

Summary Background The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. Methods In this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. Findings Among the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0.343, 95% CI 0.128-0.916, p=0.025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. Interpretation Elderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences

Update 7 May 2020

An observational study of 8,910 patients in hospitals in Asia, Europe, and North America who had either died in the hospital (5.8%) or survived to hospital discharge (94.2%). This showed an advantage with the use of ARBs but no ACEI

No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74).

1 May 2020: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 https://www.nejm.org/doi/full/10.1056/NEJMoa2007621

Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients https://www.medrxiv.org/content/10.1101/2020.03.20.20039586v1