Antiviral and anti-inflammatory drugs such as remdesivir, favipiravir and corticosteroids are those commonly prescribed to treat COVID-19 infection.

Now, a recent Swedish study is pointing to another possible treatment contender: inhaled nitric oxide (NO). While only studied within the confines of a test tube, the researchers said inhaled nitric oxide has COVID-fighting potential.

"Until we get a vaccine that works, our hope is that inhalation of NO might be an effective form of treatment," said lead author Åke Lundkvist in a news release. "The dosage and timing of starting treatment probably play an important part in the outcome, and now need to be explored as soon as possible." He is a professor in the department of Medical Biochemistry and Microbiology, Uppsala University in Sweden.

Nitric oxide is known to broaden constricted blood vessels, thereby improving blood circulation to organs. In low doses, inhaling the gas decreases inflammation and improves oxygenation in the lungs of people with acute respiratory failure, a common complication accompanying the COVID-19 disease.

If you think this is a novel treatment, it's not. In 1999, the Food and Drug Administration (FDA) allowed inhaled NO to be used to revive prematurely born infants with critical respiratory failure. However, studies warn that small dosages ( 20 parts per million or ppm), correct protocol and strict supervision are important to avoid complications.

Researchers believe some of the benefits are derived from its versatility. Nitric oxide is used to treat a wide range of bacteria, fungi and viruses. In fact, this latest study by Uppsala University is piggybacking on previous research conducted on SARS-CoV, the virus behind the first coronavirus outbreak in 2003 that affected 8,096 people in 29 countries. It shares a similar genetic sequence to SARS-CoV-2 (the virus causing COVID-19), so comparisons are relatively straightforward. In both studies the viruses did not replicate and nitric oxide proved to have an antiviral effect.

In the Uppsala study, researchers used a group of organic compounds called SNAP (S-nitroso-N-acetylpenicillamine), which have the ability to release nitric oxide, to treat copies of the virus' cells inside a test tube. The researchers tested another group of compounds without this characteristic the same way. Of the two, SNAP showed more promise. These organic compounds, also called nitric oxide donors, have been used to treat or manage various problems, including heart attacks and congestive heart failure.

U.S. Studies on Nitric Oxide

A few U.S. based projects due for completion next year are being assessed as to whether nitric oxide could help COVID-19 patients. A July review of data by George Washington School of Medicine and Health Sciences from 1993 to 2020 studied the effect of nitric oxide on respiratory illnesses. The study authors said it would help alleviate some burden on the healthcare system because fewer patients would need ventilators.

It also seems to help pregnant women. In August, six pregnant COVID-19 patients admitted to Massachusetts General Hospital were administered a high dose (160 to 200 ppm) of inhaled NO, twice a day. The study published by the journal Obstetrics and Gynecology documents how five of the six women recovered in 28 days from the severe form of the disease.

Currently, 7 active nitric oxide studies are listed on clinicaltrials.gov.

As for side effects, one review published in 2016 says, “Inhaled nitric oxide results in a transient improvement in oxygenation but does not reduce mortality and may be harmful, as it seems to increase renal impairment.”

Seema Prasad is a freelance health reporter based in Bengaluru, India. She tweets @SeemaPrasad_me

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