High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia

Valsecchi, Carlo; Winterton, Dario; Fakhr, Bijan Safaee; Collier, Ai‐ris Y.; Nozari, Ala; Ortoleva, Jamel; Mukerji, Shivali; Gibson, Lauren E.; Carroll, Ryan W.; Shaefi, Shahzad; Pinciroli, Riccardo; Vita, Carolyn La; Ackman, Jeanne B.; Hohmann, Elizabeth L.; Arora, Pankaj; Barth, William H.; Kaimal, Anjali J; Ichinose, Fumito

doi:10.1097/aog.0000000000004847

Cited by 21 publications

(15 citation statements)

References 29 publications

(82 reference statements)

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“…In addition to its effects on pulmonary function, the inhalation of NO also exhibits antiviral and anti-inflammatory properties, including the inhibition of neutrophil adhesion and the release of proinflammatory cytokines 69. Although the concentrations of inhaled NO required for antimicrobial effects remain unknown, previous studies have shown that up to 300 ppm of inhaled NO is safe and well tolerated in patients with viral pneumonia, such as COVID-1951 52 and respiratory syncytial virus pneumonia 70…”

Section: Discussionmentioning

confidence: 99%

“…It also significantly shortens the conversion time in positive patients (p=0.044) and improves the conversion rate at 7 days after treatment (82.8% vs control 66.7%, p=0.046) 48. Despite its theoretical plausibility and potential, the clinical evidence supporting the efficacy of NO in treating COVID-19-related pulmonary complications has primarily originated from observational studies49 50 or small trials,51 yielding inconsistent reported results. Recently, a phase II study demonstrated an improvement of PaO 2 /fraction of inspired oxygen (FIO 2 ) with high-dose NO (at 80 ppm) at 48 hours compared with usual care in adults with acute hypoxaemic respiratory failure due to COVID-19 52.…”

Section: Introductionmentioning

confidence: 99%

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Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial

Zheng,

Wang,

Wang

et al. 2024

BMJ Open

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BackgroundA history of SARS-CoV-2 infection has been reported to be associated with an increased risk of postoperative pulmonary complications (PPCs). Even mild PPCs can elevate the rates of early postoperative mortality, intensive care unit (ICU) admission and prolong the length of ICU and/or hospital stays. Consequently, it is crucial to develop perioperative management strategies that can mitigate these increased risks in surgical patients who have recently been infected with SARS-CoV-2. Accumulating evidence suggests that nitric oxide (NO) inhalation might be effective in treating COVID-19. NO functions in COVID-19 by promoting vasodilation, anticoagulation, anti-inflammatory and antiviral effects. Therefore, our study hypothesises that the perioperative use of NO can effectively reduce PPCs in patients with recent SARS-CoV-2 infection.Method and analysisA prospective, double-blind, single-centre, randomised controlled trial is proposed. The trial aims to include participants who are planning to undergo surgery with general anaesthesia and have been recently infected with SARS-CoV-2 (within 7 weeks). Stratified allocation of eligible patients will be performed at a 1:1 ratio based on the predicted risk of PPCs using the Assess Respiratory Risk in Surgical Patients in Catalonia risk index and the time interval between infection and surgery.The primary outcome of the study will be the presence of PPCs within the first 7 days following surgery, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm and aspiration pneumonitis. The primary outcome will be reported as counts (percentage) and will be compared using a two-proportion χ2test. The common effect across all primary components will be estimated using a multiple generalised linear model.Ethics and disseminationThe trial is approved by the Institutional Review Board of Xijing Hospital (KY20232058-F1). The findings, including positive, negative and inconclusive results, will be published in scientific journals with peer-review processes.Trial registration numberNCT05721144.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial

Zheng,

Wang,

Wang

et al. 2024

BMJ Open

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“…A recent retrospective study evaluated the use of high-dose inhaled nitric oxide for pregnant women with severe COVID-19 pneumonia [ 67 ]. Inhaled nitric oxide was associated with more oxygen supplementation-free days, and shorter length of stay in intensive care and in hospital, and did not increase adverse maternal and neonatal outcomes.…”

Section: Special Populationsmentioning

confidence: 99%

Drug treatment of COVID-19 infection

Lui

Guaraldi

2023

Current Opinion in Pulmonary Medicine

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Purpose of reviewCOVID-19 pandemic has caused more than 6.6 million deaths globally. Tremendous efforts have been committed for the development of new and repurposed drugs for the treatment of COVID-19. Although different international and national guidelines share consensus in the management of COVID-19 disease with different levels of severity, new challenges have emerged, steering the need for ongoing research in advancing the clinical management of COVID-19.Recent findingsThis review focuses on recent data from randomized trials and postmarketing real-world evidence for the treatment of mild to moderate disease in the outpatient setting and patients hospitalized for COVID-19 with varying level of severity. Relevant data for treatment of the latest omicron sub-variants in people who received vaccination are presented. Challenges in special populations, including immunocompromised hosts, patients with renal failure and pregnant women, are also discussed.SummaryTreatment of COVID-19 should be personalized according to host characteristics, degree of severity and available treatment options.

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“…Pregnant patients are at risk of developing AHRF due to pregnancy. A recent cohort study reported that iNO was associated with a reduced need for oxygen supplementation and a shorter hospital stay for pregnant patients with COVID-19 pneumonia in the absence of adverse events in mothers or infants [ 29 ], supporting the safety of iNO therapy. Although there have yet to be active debates on the effect of iNO on the clinical outcomes of COVID-19 patients [ 30 , 31 ], a number of studies have confirmed that iNO therapy is associated with improved oxygenation parameters in COVID-19 patients [ 5 , 21 , 32 ].…”

Section: No Therapy For Covid-19 Patientsmentioning

confidence: 99%

Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A Revaluation of Pauling’s Vitamin C Therapy

et al. 2023

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Linus Pauling, who was awarded the Nobel Prize in Chemistry, suggested that a high dose of vitamin C (L-ascorbic acid) might work as a prevention or treatment for the common cold. Vitamin C therapy was tested in clinical trials, but clear evidence was not found at that time. Although Pauling’s proposal has been strongly criticized for a long time, vitamin C therapy has continued to be tested as a treatment for a variety of diseases, including coronavirus infectious disease 2019 (COVID-19). The pathogen of COVID-19, SARS-CoV-2, belongs to the β-coronavirus lineage, which includes human coronavirus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). This review intends to shed new light on vitamin C antiviral activity that may prevent SARS-CoV-2 infection through the chemical production of nitric oxide (NO). NO is a gaseous free radical that is largely produced by the enzyme NO synthase (NOS) in cells. NO produced by upper epidermal cells contributes to the inactivation of viruses and bacteria contained in air or aerosols. In addition to enzymatic production, NO can be generated by the chemical reduction of inorganic nitrite (NO2−), an alternative mechanism for NO production in living organisms. Dietary vitamin C, largely contained in fruits and vegetables, can reduce the nitrite in saliva to produce NO in the oral cavity when chewing foods. In the stomach, salivary nitrite can also be reduced to NO by vitamin C secreted from the epidermal cells of the stomach. The strong acidic pH of gastric juice facilitates the chemical reduction of salivary nitrite to produce NO. Vitamin C contributes in multiple ways to the host innate immune system as a first-line defense mechanism against pathogens. Highlighting chemical NO production by vitamin C, we suggest that controversies on the therapeutic effects of vitamin C in previous clinical trials may partly be due to less appreciation of the pleiotropic functions of vitamin C as a universal bioreductant.

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High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia

Abstract: High-dose inhaled nitric oxide was associated with shorter time on supplemental oxygen and shorter intensive care unit and hospital length of stay for pregnant patients with severe coronavirus disease 2019 (COVID-19) pneumonia.

Cited by 21 publications

References 29 publications

Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial

Inhaled Nitric Oxide ReDuce postoperatIve pulmoNAry complicaTions in patiEnts with recent COVID-19 infection (INORDINATE): protocol for a randomised controlled trial

Drug treatment of COVID-19 infection

Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A Revaluation of Pauling’s Vitamin C Therapy

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