The COVID-19 pandemic is currently exacerbating another established global pandemicphysical inactivity. (1) The World Health Organization attributes approximately 3.2 million deaths per year to sedentary behavior. For many, social distancing and quarantine coupled with the systemic closure of fitness centers and public parks have imposed unique structural barriers to maintaining a physically active lifestyle. From a public health perspective, the importance of not conflating shelter-in-place with staying-in-place needs to be reinforced. Herein, exercise will be discussed as a possible therapeutic strategy to bolster resilience against COVID-19 via effects on ACE2.
Since the angiotensin converting enzyme-2 (ACE2) receptor has been acknowledged as an important cellular entry point for SARS-CoV-2, controversy has ensued regarding use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) in the management of COVID-19 patients with hypertension. Animal studies suggest that ACEi/ARBs may upregulate expression of ACE2 receptors. As such, concern arose that use of ACEi/ARBs by hypertensives might increase risk for developing COVID-19, exacerbate severity of COVID-19 morbidity and lead to increased fatal events with some further advocating for ACE2 blockade (or angiotensin II administration) as a potential strategy to mitigate viral entry of SARS-CoV-2 into ACE2 expressing cells. ACE2 via the production of Angiotensin 1-7 has anti-inflammatory and antifibrotic effects via the Mas receptor. Thus, the ACE2-Ang1-7-Mas receptor axis and the ACE-Ang II-AT1 receptor pathway may be viewed as two opposing yet complementary pathways; a duality whose balance is needed for optimal health. The binding of COVID-19 to the ACE2 binding site downregulates ACE2 and thus the ACE2-Ang1-7-Mas receptor axis, essentially over-activating the ACE-Ang II-AT1 receptor pathway. With less ACE2 available to convert angiotensin to Ang1-leading to a heightened inflammatory milieu and lung injury. At a time when many individuals are choosing to move less, the message that exercise is medicine is needed more. Exercise may be an ACE in the hole to help lower risk of COVID-19 infection and minimize the cardiopulmonary sequela during recovery.
We have no conflicts of interest to disclose.