New research suggests that catalase, a naturally occurring enzyme in humans, plants, and animals, can suppress the replication of the new coronavirus in rhesus monkeys. The results also indicate that this low cost enzyme could dampen the inflammatory response that occurs in severe COVID-19.
Above, a computer-generated illustration shows a cytokine storm, the excessive immune response that researchers are looking to prevent in COVID-19.
The COVID-19 pandemic has had a devastating effect in the United States and worldwide.
As of October 5, 2020, the Johns Hopkins Coronavirus Resource Center Dashboard reported 209,734 and 1,037,604 COVID-19-attributed deaths in the U.S. and globally, respectively. Currently, there is a lack of specific antiviral agents to treat COVID-19 and no preventive vaccine.
Some evidence suggests that severe cases of COVID-19 may be the result of an abnormal overactive immune response known as a cytokine storm. Without treatment, a cytokine storm may result in substantial morbidity and mortality.
Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.
The issue of cytokine storms
Infection with the SARS-CoV-2 virus, which causes COVID-19, triggers a local immune response. White blood cells infiltrate the tissue, causing the excessive production of reactive oxygen species (ROS).
Increased levels of ROS cause hydrogen peroxide to accumulate in tissues, leading to tissue damage, hyperinflammation, and increased viral replication. ROS further promote cytokine release.
The overproduction of inflammatory cytokines can occur in severe cases of COVID-19. Treatment to reduce the production of cytokines and the inflammatory response may, therefore, help treat this disease.
Immunosuppressive medications that doctors currently use to treat cytokine storm include steroids, intravenous immune globulin, Janus kinase inhibitors, and cytokine blockers, such as anakinra or tocilizumab. However, some of these medications are expensive, and side effects may complicate therapy.
This is where catalase comes into play. Catalase is a naturally occurring antioxidant enzyme present in the liver, red blood cells, and alveolar epithelial cells — the cells that line the insides of the alveoli in the lungs.
It effectively breaks down hydrogen peroxide in the body into oxygen and water. Catalase is also currently available as a dietary supplement and food additive.
Researchers from the University of California, Los Angeles (UCLA), the Beijing University of Chemical Technology in China, and other Chinese institutions recently speculated that catalase could decrease hydrogen peroxide levels in the body.
This, they said, could minimize downstream ROS levels and cytokine release, ultimately suppressing the excess inflammation, oxidative cell injury, and viral replication that occur in severe COVID-19.
To confirm their hypothesis, the team of scientists set out to conduct several experiments — in cell cultures and rhesus macaque monkeys — using n(CAT), catalase nanocapsules that consist of catalase molecules coated with a thin shell of polymer. This coating enhances stability and prolongs the time that catalase remains in the blood.
The researchers report their findings in the journal Advanced Materials.
Anti-inflammatory effect in cell cultures
First, the researchers assessed the effects of n(CAT) in human cell cultures. They tested the effectiveness of n(CAT) in preventing oxidative damage to human pulmonary alveolar epithelial cells.
The results indicated that n(CAT) was able to protect, as well as resuscitate, alveolar cells that had sustained damage as a result of exposure to hydrogen peroxide.
The researcher went on to culture white blood cells with n(CAT) and human alveolar cells injured by hydrogen peroxide. The addition of n(CAT) in this context also resulted in the protection and resuscitation of damaged alveolar cells.
Another experiment studied the ability of n(CAT) to control the production of cytokines in white blood cells.
The researchers found that adding n(CAT) to white blood cells resulted in significantly lower concentrations of cytokines — including tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) — in these cell cultures than in those without added n(CAT).
The addition of n(CAT) to human alveolar cells that the team had cultured with activated white blood cells also showed that n(CAT) significantly increased cell health.
These results indicate that n(CAT) can protect lung cells from certain types of injury, demonstrating an anti-inflammatory effect.
‘Far-reaching implications’
Finally, the researchers tested the effectiveness of n(CAT) in suppressing the replication of the SARS-CoV-2 virus in rhesus monkeys.
The investigators first infected all the rhesus macaques with the new coronavirus by administering the virus through the nose.
They then gave two monkeys a saline solution, phosphate-buffered saline (PBS), also through the nose. These animals acted as the control group.
Three monkeys received n(CAT) through inhalation, and two more received PBS by inhalation and n(CAT) through injection. The animals that received n(CAT) treatments did so on days 2, 4, and 6 of the experiment.
By the second day, two of the three macaques that received n(CAT) through inhalation had significantly lower viral loads of SARS-CoV-2 than the monkeys in the control group.
The two macaques that received n(CAT) intravenously also demonstrated significantly lower viral loads than the control group after day 2 of the experiment.
The administration of n(CAT) — whether intravenous or by inhalation — did not seem to cause any detectable tissue damage.
The study thus suggests that catalase can suppress the replication of SARS-CoV-2 in rhesus macaques without causing any unwanted effects. Additionally, according to the experiments in cell cultures, catalase protected alveolar epithelial cells and regulated cytokine production in white blood cells.
“There is a lot of focus on vaccines and antiviral drugs, and rightly so,” says senior author Prof. Yunfeng Lu, at UCLA.
“In the meantime,” Prof. Lu continues, “our research suggests this enzyme could offer a very effective therapeutic solution for treatment of hyperinflammation that occurs due to SARS-CoV-2 virus, as well as hyperinflammation generally.”
Study co-author Dr. Gregory Fishbein, who is Prof. Lu’s colleague at the same institution, also adds:
“This work has far-reaching implications beyond the treatment of COVID-19. Cytokine storm is a lethal condition that can complicate other infections, such as influenza, as well as noninfectious conditions, like autoimmune disease.”
Still, the study results need confirmation from future randomized controlled studies evaluating the safety and efficacy of catalase in humans who have contracted the SARS-CoV-2 virus. Only then will researchers be able to establish whether this enzyme is truly effective in treating COVID-19.
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