Scientists with the University of Virginia School of Medicine have shown that endurance exercise may help to protect against severe health damage from Coronavirus.
The scientists – led by Dr. Zhen Yan – point out that oxidative stress can lead to and exacerbate many of the things which can lead to death from Coronavirus: Acute Respiratory Distress Syndrome (ARDS), cytokeine storm, and multi-organ failure.
An announcement from the University of Virginia points out:
Research conducted prior to the pandemic suggested that approximately 45% of patients who develop severe ARDS will die.
And the University of California at San Francisco Medical School notes:
The leading cause of death in COVID-19 patients is acute respiratory distress syndrome (ARDS), a form of oxygen starvation associated with the flooding of the tiny air sacs within the lungs called the alveoli.
Although treatment has greatly improved over the past two decades, ARDS arising from influenza infections still kills thousands of patients each year in the United States, notes UCSF pulmonologist and critical care specialist Matthay. The number of COVID-19 deaths due to ARDS is expected to be much greater.
“Most of the mortality in COVID-19 is due to severe ARDS,” Matthay said. “Somewhere between about 17 percent to 30 percent of hospitalized COVID-19 patients are ending up with ARDS, and about 40 to 50 percent who develop ARDS are dying, based on data from China and some regions of the U.S.”
ARDS in very difficult to treat – especially in patients weakened in other ways – which largely explains why so many people are dying from Coronavirus.
But in a new study, Yan shows that cardio exercise releases a chemical called “extracellular superoxide dismutase” (EcSOD for short), and circulates it to the lungs, organs and peripheral tissues. This reduces the oxidative stress on those vulnerable parts of the body, reducing the likelihood that ARDS, cytokein storms, and mulit-organ failure develop.
Exercise may even help to partially explain why most people don’t get very sick from Coronavirus, but some people – especially those who are obese – are at much higher risk (since frequent aerobic exercise can help prevent death from Coronavirus and tends to be associated with less obesity):
“All you hear now is either social distancing or ventilator, as if all we can do is either avoid exposure or rely on a ventilator to survive if we get infected,” Yan said. “The flip side of the story is that approximately 80% of confirmed COVID-19 patients have mild symptoms with no need of respiratory support. The question is, ‘Why?’ Our findings about an endogenous antioxidant enzyme provide important clues and have intrigued us to develop a novel therapeutic for ARDS caused by COVID-19.”
This potent antioxidant [EcSOD] hunts down harmful free radicals, protecting our tissues and helping to prevent disease. Our muscles naturally make EcSOD, secreting it into the circulation to allow binding to other vital organs, but its production is enhanced by cardiovascular exercise.] hunts down harmful free radicals, protecting our tissues and helping to prevent disease. Our muscles naturally make EcSOD, secreting it into the circulation to allow binding to other vital organs, but its production is enhanced by cardiovascular exercise.
A decrease in the antioxidant is seen in several diseases, including acute lung disease, ischemic heart disease and kidney failure, Yan’s review shows. Lab research in mice suggests that blocking its production worsens heart problems, while increasing it has a beneficial effect. A decrease in EcSOD is also associated with chronic conditions such as osteoarthritis.
Research suggests that even a single session of exercise increases production of the antioxidant ….
“We cannot live in isolation forever,” he said. “Regular exercise has far more health benefits than we know. The protection against this severe respiratory disease condition is just one of the many examples.”
We sent Dr. Yan a Swiss study from 2014 regarding oral SOD supplements, and asked him whether oral SOD supplements can provide protection against ARDS and other disease worsened by Coronavirus. Dr. Yan responded:
I noticed this paper. If the combination would stimulate EcSOD production in the body, it may have the same benefit. However, the SOD supplement itself is different from EcSOD. EcSOD has HBD and can specifically bind to vital organs in the right place to scavenge superoxide. None of the other antioxidants and antioxidant enzymes has this property. Intake SOD will unlikely stimulate EcSOD expression as our body needs stimuli to promote an adaptive response (the concept of homeostasis).
We do not lack of clinical trials of using antioxidants in various oxidative stress-related diseases, most of them failed. I believe it is due to the fact that we naively thought that simply increasing antioxidant would cure the disease. EcSOD is different. Lung tissue has the highest level of EcSOD, hence EcSOD is particularly protective against lung diseases, including ARDS.
In other words, aerobic exercise – which is free and widely available – is more protective than expensive supplements.
I also asked Dr. Yan if the furin-binding property of EcSOD which he noted in his study may also help prevent severe damage from Coronavirus:
Because Covid19 has an unusual spike protein which can cleave to furin (see https://www.nature.com/articles/d41586-020-00660-x), do you think that EcSOD may inhibit Covid’s ability to interact with furin?
He responded:
The possibility cannot be ruled out. Generally speaking, when two proteins interact with the same protein, they may compete against each other.
Postscript: For those interested in learning more, below are some interesting quotes from Dr. Yan’s scientific paper:
Oxidative stress has been shown to play an important role in many disease pathologies, such as … acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).
***
EcSOD is widely expressed in many tissues/organs with the highest levels in the lung and kidney. EcSOD is so far the only known antioxidant enzyme that functions to scavenge biologically toxic O2.- in the extracellular space.
***
Finally, EcSOD has a heparin binding domain (HBD) on the C-terminus, consisting of six positively charged lysine and arginine residues. This HBD is responsible for EcSOD binding to proteoglycans, such as heparin, collagen and fibulin, which allows for EcSOD localization to the cell surface and extracellular matrix. In order for EcSOD to be released into plasma and other fluids, carboxylases and furin-like proteases have to cleave EcSOD near the HBD.
***
Exercise-induced EcSOD expression seems to be specific for endurance exercise, not induced by resistance exercise.
***
Exercise-induced increase of EcSOD promotes removal of O2.- and preserved NO availability to effectively prevent endothelial dysfunction. C) O2.- stimulates pro-inflammatory cytokines and expression of cell surface adhesion molecules, such as VCAM-1, ICAM-1, and E-selectin.
***
Considering the current outbreak of the 2019 Novel Corona virus infection (COVID-19), which is an infectious disease that leads to progressive ALI/ARDS in many patients, it is conceivable that regular exercise might be effective in preventing while EcSOD gene/protein therapy might be effective in treating ALI/ARDS under the condition of COVID-19 infection.
***
Multiple Organ Dysfunction Syndrome (MODS), a major contributor of intensive care unit (ICU) mortality, occurs when multiple organs are damaged to the point where they cannot maintain homeostatic function. Emerging evidence suggests that oxidative stress-induced endothelial cell activation (induced expression of adhesion molecules) in vital organs is a key step in the pathology as it leads to exacerbated inflammatory cell infiltration and tissue damage. *** we demonstrated that EcSOD protected against LPS-induced MODS by preserving lung function, reducing endothelial cell activation, and decreasing endothelial cell adhesion.”