key: cord-0732056-5omr52n7
authors: Gupta, Ritesh
title: Letter to the Editor in Response to article: “Clinical considerations for patients with diabetes in times of COVID-19 epidemic (Gupta et al.)
date: 2020-04-18
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2020.04.023
sha: 6805a99a3c5a410c7729fc088e03c8c8f3ba8571
doc_id: 732056
cord_uid: 5omr52n7

nan

Dear editor, We recently published an article highlighting the special concerns while managing patients with diabetes in the times of COVID-19 pandemic i . There have been some concerns about the use of Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), which were not clarified in our publication ii . We are summarising the current evidence in this regard and will try to arrive at a reasonable conclusion.

In the absence of a vaccine and an antiviral drug for the COVID-19 infection, several therapeutic approaches are being studied. One such approach is the use of inhibitors of the renin angiotensin system, namely ACE inhibitors and ARBs. On the other hand, some concern has been raised about the fact that patients on these agents might be at an increased risk of infection by Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2).

Angiotensin converting enzyme-2 (ACE-2) is the receptor for SARS CoV-2 as well as other coronaviruses and is expressed in type 2 alveolar epithelial cells and endothelium. The Sglycoprotein on the surface of coronavirus binds to ACE2. This leads to a conformational change in the S-glycoprotein and allows proteolytic digestion by host cell proteases (TMPRSS2) ultimately leading to internalization of the virion iii . Viral S-glycoprotein, TMPRSS2 and ACE-2 inhibition are potential targets of therapy and possibly vaccine development.

As ACE-2 is essential to coronavirus infection, its blockade is thought to be beneficial in preventing/treating this infection. A retrospective analysis found reduced rates of death and endotracheal intubation in patients with viral pneumonia who were continued on ACE inhibitors iv . Mice with coronavirus induced lung injury showed improvement when treated with losartan v . As far as CVID-19 infection is concerned, the data on RAS activation or the effect of its blockade is limited at present. Hypokalaemia could be a marker of RAS activation and high incidence of hypokalaemia has been reported in patients with COVID-19 infection vi .

Despite these small studies suggesting the benefit of drugs acting on RAS, there is some data, albeit scarce, from animal models and human studies that treatment with ACE inhibitors and ARB could cause up regulation of ACE2 vii . Ibuprofen and thiazolidinediones have also been shown to do the same viii,ix . Increased expression of ACE2 could theoretically increase the risk of infection with SARS CoV-2. This could be a concern in people with diabetes who are at already elevated risk of infections because of many other factors. However, currently, there is no evidence to support this hypothesis. In view of lack of robust evidence for either benefit or harm, it is reasonable for patients to continue using ACE inhibitors and ARB, as recommended by European Society of Cardiology Council on Hypertension and European Society of Hypertension. x,xi .

Fortis CDOC Hospital for Diabetes and Allied Sciences, Chirag Enclave, New Delhi, India Correspondence to: riteshgupta72@gmail.com

Clinical considerations for patients with diabetes in times of COVID-19 epidemic

Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?

The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for e ntry into target cells

Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia

Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virusinduced acute lung injury

Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19)

The vasoprotective axes of the renin-angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases

Ibuprofen attenuates cardiac fibrosis in streptozotocin-induced diabetic rats

Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis

x Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers

xi ESH Statement on COVID-19