Antiviral and anti-inflammatory drugs like remdesivir, favipiravir, and corticosteroids are commonly prescribed to treat COVID-19 infections.

A recent Swedish study now points to another possible treatment candidate: inhaled nitric oxide (NO). While only examined inside a test tube, the researchers said inhaled nitric oxide has COVID-fighting potential.

“Until we get a vaccine that works, we hope that inhaling NO will be an effective form of treatment,” lead author Åke Lundkvist said in a press release. “The dosage and when to start treatment are likely to play an important role in the outcome and need to be investigated as soon as possible.” He is a professor at the Institute of Medical Biochemistry and Microbiology at Uppsala University in Sweden.

It is known that nitric oxide widens narrowed blood vessels and thereby improves blood flow to organs. In low doses, inhaling the gas reduces inflammation and improves the oxygen supply to the lungs of people with acute respiratory failure, a common complication associated with COVID-19 disease.

If you think this is a novel treatment, it is not. In 1999 the Food and Drug Administration (FDA) approved the use of inhaled NO for resuscitation of premature babies with critical respiratory failure. However, studies caution that small dosages (20 ppm), proper protocol, and close monitoring are important to avoid complications.

Researchers believe some of the benefits come from its versatility. Nitric oxide is used to treat a wide variety of bacteria, fungi, and viruses. In fact, this latest study from Uppsala University is based on previous research into SARS-CoV, the virus behind the first coronavirus outbreak in 2003 that affected 8,096 people in 29 countries. It has a similar genetic sequence to SARS-CoV-2 (the virus that causes COVID-19) so comparisons are relatively easy. In both studies, the viruses did not replicate and nitric oxide showed antiviral effects.

In the Uppsala study, researchers used a group of organic compounds called SNAP (S-nitroso-N-acetylpenicillamine) that can release nitric oxide to treat copies of the virus cells in a test tube. The researchers tested another group of compounds without this property in the same way. Of the two, SNAP showed more promise. Also called nitric oxide donors, these organic compounds have been used to treat or treat various problems, including heart attacks and heart failure.

US studies on nitric oxide

Some projects in the US, slated for completion in the next year, are currently being evaluated to see if nitric oxide could help COVID-19 patients. A July review of the George Washington School of Medicine and Health Sciences data from 1993 to 2020 examined the effects of nitric oxide on respiratory diseases. The study’s authors said this would help take some pressure off the health system as 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 given a high dose (160 to 200 ppm) of inhaled NO twice daily. The study, published by the journal Obstetrics and Gynecology, documents how five of the six women recovered from the severe form of the disease within 28 days.

There are currently 7 studies on active nitrogen oxides listed on clinicaltrials.gov.

Regarding side effects, a review published in 2016 states: “Inhaled nitric oxide temporarily improves oxygenation, but does not reduce mortality and can be harmful as it appears to increase kidney dysfunction.”

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

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