SARS-CoV-2 and Other Respiratory Viruses: What Does Oxidative Stress Have to Do with It?

Figure 2

Viral entry and oxidative stress in different organs. SARS-CoV-2 can affect the lungs as well as other important organs influenced by oxidative stress. Due to the high availability of long-chain fatty acids in nerve cells in the brain and CNS, oxidative stress induced by viral entry through the ACE2 receptor and the TMPRSS2 serine protease can cause considerable damage in this system. Unbalanced RAS activation may lead to hypoxia, direct viral injury, immune-mediated damage, and ACE2 shedding. In the heart, coronaviruses cause damage, since the virus is able to directly invade cardiomyocytes, cells in the form of fibers that make up the heart muscle. In cardiac manifestations, the cytokine storm (especially represented by IL-6, TNF and IL-1β) plays an important role and generates oxidative stress. Such effects lead to an increase in local hypoxia, tissue injury, and REDOX imbalance. In addition, increased NOX-2 enzyme production may represent an important element considering cardiac oxidative stress and myocardial damage in COVID-19 patients. In the lungs, which are the organs most affected by infection, the virus enters alveolar and epithelial cells through the ACE2 receptor and the TMPRSS2 serine protease, which triggers the recruitment of immune cells to the infection site, leading to excessive production of proinflammatory cytokines and NOX enzyme activation. The cytokine storm can lead to the activation of MAPKs and therefore the activation of NFκB, the major nuclear factor related to inflammatory responses. All of these activation pathways lead to mitochondrial dysfunction and excessive ROS production.