key: cord-0745032-cvce4gtl
authors: Kow, Chia Siang; Hasan, Syed Shahzad
title: The potential benefit of telmisartan to protect overweight COPD patients from the acquisition of COVID‐19
date: 2020-07-21
journal: Obesity (Silver Spring)
DOI: 10.1002/oby.22976
sha: 5eafce22d6c45a5341df22f5677b690e6fe0046d
doc_id: 745032
cord_uid: cvce4gtl

Individuals with chronic obstructive pulmonary disease (COPD) have long been identified to have an elevated serum level of angiotensin‐converting enzyme 2 (ACE2), the cellular entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The newest discoveries by Higham et al. (1) were the increased ACE2 expression in the bronchial epithelium of overweight COPD patients compared to their non‐overweight counterparts.

This article is protected by copyright. All rights reserved Disclosure: The authors declared no conflict of interest. No funding was received for the writing of this manuscript.

Individuals with chronic obstructive pulmonary disease (COPD) have long been identified to have an elevated serum level of angiotensin-converting enzyme 2 (ACE2), the cellular entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The newest discoveries by Higham et al. [1] were the increased ACE2 expression in the bronchial epithelium of overweight COPD patients compared to their non-overweight counterparts.

Given the fact that higher expression of ACE2 may lead to an increased risk of severe course of COVID-19, there are potential benefits of using angiotensin receptor blockers (ARBs) among overweight COPD patients. In its native state, the angiotensin type I receptor (AT 1 R), binds to ACE2 to form a receptor complex [2] . ARBs stabilize the ACE2-AT 1 receptor complex on the cell membrane and thus prevent interaction of the SARS-CoV-2 with ACE2 catalytic site. Even if ARBs could not eliminate the viral entry, ARBs could also block the binding of excess angiotensin II (from downregulation of ACE2 following hijack by SARS-CoV-2) to AT 1 R and thus mitigate angiotensin II-mediated lung injury and development of acute

This article is protected by copyright. All rights reserved respiratory failure. In addition, ARBs possess anti-inflammatory actions with their ability to utilize the ACE2/Angiotensin II type 2 receptor/Mas receptor pathway that could limit cytokine storm induced by SARS-CoV-2.

On the other hand, many may not recognize the effects of ARBs on body weight. Specifically, telmisartan could prevent adipogenesis and weight gain. Telmisartan has been shown to upregulate the expression and activity of peroxisome proliferator-activated receptor (PPAR)-δ in 3T3-L1 preadipocytes in a dosedependent fashion. The subsequent activation of PPAR-δ-dependent lipolytic pathway by telmisartan reduced adipogenesis in vitro [3] . In vivo, long-term administration of telmisartan significantly reduced the increase in body weight and prevented high-fat diet-induced obesity through increased expression of PPAR-δ and several lipolytic and energy uncoupling-related proteins in adipose tissue and skeletal muscle in wild-type mice and spontaneously hypertensive rats [3] . In fact, a human study of 32 patients with type 2 diabetes and metabolic syndrome who received telmisartan demonstrated a significant decline in body mass index as well as waist circumference at 6 months compared to baseline [4] .

We are aware of some human and animal studies showing an increased ACE2 expression with the administration of ARBs other than telmisartan, but such observation may not translate to greater susceptibility towards COVID-19. Specifically, a study which included only 1.6% (621/37031) of COPD patients reported no difference in the risk of acquiring COVID-19 between ARB users and non-ARB users though the protective effect of ARBs towards the acquisition of COVID-19 may be more apparent among overweight COPD patients who may have higher baseline risk of acquiring COVID-19 [5] . We recognized that no evidence thus far has shown that ARBs or specifically telmisartan could prevent or lead to better clinical outcomes among overweight COPD patients with COVID-19. Nevertheless, we hope that our discussion above on the potential beneficial effects of telmisartan can serve to stimulate an interest to trial telmisartan for the prevention and management of COVID-19 in overweight COPD patients due to its dual benefits: prevent/mitigate COVID-19 along with weight reduction.

Increased ACE2 Expression in the Bronchial Epithelium of COPD Patients who are Overweight

Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an angiotensin II type I receptor-Accepted Article This article is protected by copyright. All rights reserved dependent mechanism

Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways

Telmisartan reduced abdominal circumference and body weight with decreasing triglyceride level in patients with type 2 diabetes and metabolic syndrome

Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19