Inhaled Nitric Oxide Is Virucidal, Kills SARS-CoV-2: Amrita University Study

Researchers from Amrita Vishwa Vidyapeetham and Amrita Hospital have conducted a study to evaluate the effectiveness of repurposed inhaled nitric oxide in improving clinical outcomes in Covid-19.

Nitric Oxide molecular model (left); SARS-CoV-2 Being Destroyed (right) (Photos: Getty)

New Delhi: Scientists from the School of Biotechnology at Amrita Vishwa Vidyapeetham, a Coimbatore-based private deemed-university, and doctors from the Amrita Hospital, Kochi have explored a novel intervention for Covid-19 with the well-known gas Nitric Oxide (NO), in a new study. 

For many years, the gas has been used worldwide for the treatment of medical conditions like the Blue Baby Syndrome and for the treatment of heart or lung transplant patients. Blue Baby Syndrome, or Infant methemoglobinemia, is a condition where a baby's skin turns blue, and happens when there is not enough oxygen in the blood.

The study, titled "Clinical Efficacy of Inhaled Nitric Oxide in Preventing the Progression of Moderate to Severe COVID-19 and Its Correlation to Viral Clearance – Results of a Pilot Study", was recently published in the journal, Infectious Microbes & Diseases.

Hypoxic patients with Covid-19 are at high risk of adverse outcomes. Hypoxia is the condition of absence of enough oxygen in the tissues to sustain bodily functions. Inhaled Nitric Oxide (iNO) has shown antiviral and immunomodulatory (regulatory adjustment of immune system) effects in vitro (process taking place outside a living body), the authors noted in the study. 

Effectiveness Of Repurposed Inhaled Nitric Oxide In Improving Covid-19 Outcomes

There is very little evidence of the effects of the therapy in hypoxic Covid-19 patients in vivo (inside a living body).

Therefore, the researchers conducted an open label feasibility study at a single referral centre in South India, and evaluated the effectiveness of repurposed iNO in improving clinical outcomes in Covid-19. The researchers also evaluated the correlation of repurposed iNO with viral clearance.

The study found that iNO is virucidal and kills SARS-CoV-2, apart from preventing its effective attachment to human host cells.

The feasibility trial conducted at Amrita Hospital found that Covid-19 patients who received the iNO therapy recovered faster with lesser complications and zero mortality rates compared to patients who received the standard Covid-19 treatment without iNO.

Professor Geetha Kumar, Dean, Physical Sciences at Amrita, said that the researchers' interest in looking at Nitric Oxide as a treatment option for Covid-19 stemmed from an early study conducted by a Swedish group, according to a statement issued by Amrita Vishwa Vidyapeetham. She said that the Swedish study had suggested that the gas can prove effective in curbing SARS-CoV-2, because it induces biochemical changes which directly affect the spike protein of the virus. 

The spike protein is the main culprit in interacting with the human body's receptors and immune system and creating havoc. 

The team of experts at Amrita Hospital was headed by Dr. Aveek Jayant, Dr. Thushara Madathil, Dr. Dipu T.S, and Dr. Merlin Moni. The researchers decided to conduct this trial on a small group of Covid-19 patients admitted at Amrita Hospital, the statement said. As many as 14 out 25 patients selected for the study were given iNO along with standard treatment for Covid-19, according to the study. 

The Control standard treatment group included 11 patients. The patients treated with iNO therapy showed a significant drop in their viral load, the authors found in the study.

"The study by Amrita Hospital successfully demonstrates the putative role of repurposed inhaled Nitric Oxide in hypoxemic Covid-19 patients," according to Dr Merlin. She said that the expert panel associated with the study now calls for an extended validation to take this treatment process to the next level, according to the statement.

Dr Bipin Nair said: "As the global search for an effective remedy against Covid continues, this strategy to use Nitric Oxide as a therapeutic measure has the scope to be a successful, rapid and affordable game-changer in the fight against the pandemic." He further said that it is conceivable that healthcare workers, who are constantly exposed to the coronavirus, could also use this as a prophylactic while treating infected patients. A prophylactic is a medicine or substance that prevents disease.

He added that this approach to repurpose Nitric Oxide has the potential to be an effective preventative, especially in light of the highly infectious nature of the Omicron variant prevalent today.

No Deaths In Treatment Group Administered With iNO Therapy

The proportion of patients progressing to mechanical ventilation in the control group was significantly higher than that in the treatment group, the study said. This is because four out of 11 patients were observed to progress to mechanical ventilation in the control group, while no patient progressed to mechanical ventilation in the treatment group. 

As many as 4 patients out of 11 patients died in the control group, while none died in the treatment group. 

The numbers needed to treat (NNT) to prevent an additional poor outcome of death was estimated to be 2.8, the study said. However, a significant decrease was not observed between the treatment and control groups for the length of inpatient stay and the length of ICU stay.

No Patient Developed The Adverse Event Of Methemoglobinemia

The experts monitored the incidence of methemoglobinemia, which was the adverse event in the study. As per the adverse event definition during the treatment period, none of the patients in the treatment group developed methemoglobin levels greater than three per cent, the study said.

Nitric oxide has been shown to have a direct effect on inhibiting the replication of SARS-CoV-2, the study said. NO causes a reduction in viral RNA production in early steps of viral replication, and can modulate immunopathology. 

All the patients in the treatment group achieved the normalised Ct Value, corresponding to a negative result of Covid-19 by day 5. This demonstrated a faster viral clearance in the treatment group compared with the control group.

In the study, Ct value was used as the closest surrogate marker to understand viral dynamics during the hypoxic phase. The authors acknowledged the fact that Ct value is not a direct measurement of viral replication. The observed viral decline correlated well with the clinical outcomes, the study said. 

"Our study demonstrates the putative role of repurposed iNO in hypoxemic Covid-19 patients and calls for extended validation," the authors noted in the study.