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. 2021 Nov 15:12:747200.
doi: 10.3389/fphys.2021.747200. eCollection 2021.

Moderate Intensity Aerobic Exercise Potential Favorable Effect Against COVID-19: The Role of Renin-Angiotensin System and Immunomodulatory Effects

Hamid Arazi  1 , Akram Falahati  1 , Katsuhiko Suzuki  2
Affiliations

Moderate Intensity Aerobic Exercise Potential Favorable Effect Against COVID-19: The Role of Renin-Angiotensin System and Immunomodulatory Effects

Hamid Arazi et al. Front Physiol. .

Abstract

The coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus (CoV) named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the angiotensin converting enzyme 2 (ACE2) is the cellular receptor of SARS-CoV-2, it has a strong interaction with the renin angiotensin system (RAS). Experimental studies have shown that the higher levels of ACE2 or increasing ACE2/ACE1 ratio improve COVID-19 outcomes through lowering inflammation and death. Aerobic moderate intensity physical exercise fights off infections by two mechanisms, the inhibition of ACE/Ang II/AT1-R pathway and the stimulation of ACE2/Ang-(1-7)/MasR axis. Exercise can also activate the anti-inflammatory response so that it can be a potential therapeutic strategy against COVID-19. Here, we summarize and focus the relation among COVID-19, RAS, and immune system and describe the potential effect of aerobic moderate intensity physical exercise against CoV as a useful complementary tool for providing immune protection against SARS-CoV-2 virus infection, which is a novel intervention that requires further investigation.

Keywords: SARS-CoV-2; coronavirus; immune protection; inflammation; renin angiotensin system.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Role of ACE1 and ACE2 in the renin-angiotensin-aldosterone system (RAAS). ACE, ACE2, angiotensin converting enzymes; AT1-R, AT2-R, angiotensin 1 and 2 receptors; Mas-R, Mas receptor.
FIGURE 2
FIGURE 2
Schematic representation of the main molecular pathways activated by SARS-CoV-2 and aerobic physical exercise and their respective consequences. On the right of the panel, the SARS-CoV-2 is shown, which relies upon ACE2 and TMPRSS2 to enter the host cells. SARS-CoV-2 upregulates the expression of ACE1/Ang-II/AT1R and inhibits the MasR which results in exacerbating inflammatory response. Contrarily, a shifted RAS balance toward the ACE2/Ang 1–7/Mas receptor axis after aerobic physical exercise was a reason for defensive outcomes. Furthermore, exercise activates PGC-1α-FNDC5/Irisin pathway. Irisin play an important role in anti-inflammatory pathways including Nrf2. Nrf2 results in transformation of cells subject to oxidative stress. In normal circumstances, Nrf2 is placed in the cytoplasm bound to its Keap1, which is its inhibitor. When ROS caused by exercise is available, the Keap1 and Nrf2 connection detaches and Nrf2 moves to the nucleus, where it arouses the antioxidant and anti-inflammatory activity. MIAE, Moderate intensity aerobic exercise; ACE2, Angiotensin converting enzyme2; Ang II, Angiotensin II; Ang 1–7, Angiotensin 1–7; AT1R, Angiotensin II receptor type 1; MAS R, Mas receptor; ROS, Reactive Oxygen Species; FNDC5, fibronectin type III domain-containing protein 5; PGC-1α, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; TMPRSS2, Transmembrane serine protease 2; Nrf2, nuclear factor erythroid 2–related factor 2; KEAP1, Kelch-like ECH-associated protein 1.
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