Tuesday, March 24, 2020

Hypertension and diabetes mellitus increase the risk for COVID-19 infection?

Electron microscope image shows SARS-CoV-2 (Round Gold Objects)

As per three studies conducted by Chinese scholars,

Study 1: By Xiaobo Yang and colleagues
The major additional condition on 32 non-survivors from a group of 52 COVID-19 ICU patients were cerebrovascular diseases (22%) and diabetes (22%)

Study 2: By Guan W and others
Out of 1099 COVID-19 patients, 173 had severe heart disease along with hypertension (23.7%), diabetes mellitus (16·2%), coronary heart diseases (5·8%), and cerebrovascular disease (2·3%)

Study 3: By Zhang JJ and others
Out of 140 COVID-19 patients, 30% had hypertension and 12% had diabetes.

This is a study with a small group of patients. It is very much possible that, the results may find incorrect in the future. However, let's see how the above-mentioned diseases affect coronavirus.

It’s here we need to understand the role of ACE2 (Angiotensin-Converting Enzyme 2) in our body. This is a very important enzyme. ACE2 attaches to the outer surface of cells in the lungs, arteries, heart, kidney, and intestines. The advantage of ACE2 is this enzyme reduces blood pressure. The problem is, ACE2 is believed to be the entry point for some coronaviruses like HCoV-NL63, SARS-CoV (this virus caused SARS outbreak in the past) and SARS-CoV-2. It is SARS-COV-2 which causes COVID-19.

In order to connect the dots, we need to learn about ACE (Angiotensin-converting enzyme) as well.  ACE controls blood pressure by regulating the volume of fluids in the body. ACE indirectly increases blood pressure by causing blood vessels to become narrower especially by encircling pressure. Because of this behavior, ACE inhibitors are used for the treatment of cardiovascular diseases.

Well, to reduce blood pressure, people with the above diseases are treated with ACE inhibitors and Angiotensin Receptor Blockers (ARB). Both might result in an increase of ACE2 and might increase the severity of Coronavirus infection.

The above reports quickly spread through social media and people stopped taking those medicines. The above-mentioned theory is contested and 'The American Heart Association', the 'Heart Failure Society of America' and the 'American College of Cardiology' issued a joint statement on March 17 and the 'European Society of Cardiology' issued a statement on March 13 against it. The Nephrology Journal Club issued a review with a similar message on March 17. 

Recently published in an article in 'European Heart Journal', "SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19?" by Gabriela M Kuster and others states this may not be the case (although not so convincingly) and recommended the continuing usage (a bit convincingly) of medicines.

Counter-arguments they put forward are, 
1. "ACE2 expression may not necessarily correlate with the degree of infection. Although ACE2 is thought to be mandatory for SARS-CoV infection, absence of SARS-CoV was observed in some ACE2 expressing cell types, whereas infection was present in cells apparently lacking ACE2, suggesting that additional co-factors might be needed for efficient cellular infection"
In lay man's terms, even if the belief is ACE2 is mandatory for SARS-CoV infection (COVID-19), there are cases where a) disease simply didn't affect cells which has ACE-2 and b) cells which don't has ACE2 was affected. 
2. "lethal outcome of COVID-19 is mostly driven by the severity of the underlying lung injury"
3. "mouse model of SARS-CoV infection and pulmonary disease, a key pathophysiological role was shown for ACE... SARS-CoV spike protein led to down-regulation of ACE2 and more severe lung injury in mice that could be attenuated by administration of an ARB. These findings suggest a protective role of ARB in SARS-CoV associated lung injury and give rise to the hypothesis that primary activation of the RAAS in cardiovascular patients, rather than its inhibition, renders them more prone to a deleterious outcome"
In layman's terms, SARS-Cov (COVID-19) led to lower ACE2 and severe lung injury in mice. 
4. "Earlier mentioned studies do not report how many patients were taking ACE-Is or ARBs. Based on data from China PEACE Million Persons Project, nearly half of Chinese adults between 35 and 75 years are suffering from hypertension, but fewer than one third receive treatment and blood pressure control is achieved in less than 10%"
5. "patients taking ACE-Is or ARBs may be more susceptible for viral infection and have higher mortality because they are older, more frequently hypertensive, diabetic, and/or having renal disease."
In layman's terms, patients taking these medicines are very old and there may be other contributing factors.
Basically, this paper argues that ACE-I and ARB therapy should be maintained/initiated in patients with heart failure, hypertension, or myocardial infarction according to current guidelines irrespective of SARS-CoV2. After all these medicines result in mortality reduction for people with cardiovascular diseases. 

Well, one can't say this way or another. I hope that more evidence will come and hopefully people will reach a better conclusion. Meanwhile, don't be your doctor and start/ stop/ switch medicines based on what you read on social media and newspapers. Consult with your physician and follow their advice.



1. Yang X, Yu Y, Xu J and others
Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.
Lancet Respir Med. 2020 (pub Feb 24)

2. Guan W, Ni Z, Hu Y and others
Clinical characteristics of coronavirus disease 2019 in China.
N Engl J Med. 2020 (pub Feb 28)

3. Zhang JJ, Dong X, Cao YY and others
Clinical characteristics of 140 patients infected by SARS-CoV-2 in Wuhan, China.
Allergy. 2020; (pub 19)

4. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext

6. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa235/5810479

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