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COVID-19 has affected more than a million people across the world by now. Though there is still no treatment for the disease, scientists all over the world are rushing to find ways to manage it and keep the infection from worsening.

The latest in this series of symptomatic treatments is the use of nitric oxide gas. Researchers in Italy and some other places are considering using inhaled nitric oxide to treat severe cases of COVID-19. The gas is being tested in clinical studies to test its efficiency.

Nitric oxide is an odourless and colourless gas that causes dilation of blood vessels in the lungs. It is normally produced in various tissues in our body and plays a role in triggering the immune system to work against harmful pathogens, dilation of blood vessels and in the process of signal transduction in the brain.

The gas is clinically used to treat pulmonary hypertension - high blood pressure in the blood vessels of the lungs. Some of the conditions that can cause pulmonary hypertension include chronic obstructive pulmonary disease (COPD) and sickle cell disease

Nitric oxide: How it works

Nitric oxide, when inhaled, crosses the membranes of capillaries (very thin blood vessels) in the alveoli (air sacs of lungs). Once there, it starts a series of reaction in the lungs which lead to the formation of a compound called cGMP (cyclic guanosine 3', 5' monophosphate), which in turn relaxes the smooth muscles in its vicinity and results in vasodilation (widening of blood vessels). 

Apart from vasodilation, NO also has anti-inflammatory and bronchodilatory effects. (A bronchodilator is something that widens the airways of the lungs.)

To perform its function, NO first activates an enzyme called soluble guanylyl cyclase, which then goes and converts a compound called GTP (Guanosine-5'-triphosphate) into cGMP. As the concentration of cGMP increases inside the body cells, it starts to exert its effect on the smooth muscles. 

cGMP is normally broken down by an enzyme called PDE5. However, the action of PDE5 can be inhibited by compounds like sildenafil (viagra), zaprinast, and vardenafil.

Read more: COVID-19: What is oxygen therapy

Nitric oxide and Coronavirus

A randomised clinical trial with around 200 COVID-19 patients is currently underway to find out if NO can be used effectively for reducing the severity of the disease. The research is being sponsored by the Masscheussetes General Hospital and is being done in collaboration with Xijing Hospital, China. It aims to improve the blood oxygen status of hypoxia patients within 48 hours of enrollment and to improve the survival rate of enrolled patients. (One of the signs that COVID-19 disease is progressing in a patient is severe shortness of breath.)

Nitric oxide has previously been used to reduce the severity of symptoms in the SARS epidemic of 2003. In the case of SARS, NO inhalation reduced hypoxia (reduced tissue oxygen levels), reversed pulmonary hypertension and significantly reduced the length of ventilator support time for patients with severe disease. 

Laboratory-based studies show that NO introduction suppresses the replication of SARS-CoV, the virus that caused SARS, suggesting the antiviral effects of NO treatment. 

Read more: Ventilators for COVID-19 patients should have these special features 

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  1. National Heart, Lung, and Blood Institute [Internet]. Bethesda (MD): U.S. Department of Health and Human Services; Pulmonary Hypertension
  2. Ichinose Fumito, Roberts Jr Jesse D., Zapol Warren M. Inhaled Nitric Oxide: A Selective Pulmonary Vasodilator: Current Uses and Therapeutic Potential. Circulation. 2004; 109(25):3106-3111.
  3. Clinical [Internet]. National Institute of Health. US National Library of Medicine; Nitric Oxide Gas Inhalation for Severe Acute Respiratory Syndrome in COVID-19. (NOSARSCOVID)
  4. Clinical [Internet]. National Institute of Health. US National Library of Medicine; Nitric Oxide Gas Inhalation in Severe Acute Respiratory Syndrome in COVID-19 (NOSARSCOVID)
  5. Åkerström Sara, et al. Nitric Oxide Inhibits the Replication Cycle of Severe Acute Respiratory Syndrome Coronavirus. Journal of Virology. 2005; 79(3): 1966-1969.
  6. Bescós R, Sureda A, Tur JA, Pons A. The effect of nitric-oxide-related supplements on human performance. Sports Med. 2012;42(2):99–117. PMID: 22260513.
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