Breathing nitric oxide at high dose in severe-critical COVID-19 during pregnancy: A case series

Introduction: Pregnant patients with a severe form of COVID-19 are at increased risk of maternal and fetal complications. Nitric Oxide (NO) gas is a selective pulmonary vasodilator currently approved to treat newborns with pulmonary hypertension. Inhaled NO has been safely used in patients with severe pneumonia and for cases of pregnant patients with pulmonary hypertension. The antimicrobial effect of NO has been confirmed against bacteria and viruses. In vitro study demonstrated a dose-dependent effect of NO against SARS-CoV-1 and 2. We hypothesize that breathing NO at 160-200 ppm twice daily for 30 minutes in spontaneously breathing pregnant patients might provide a safe and effective treatment for COVID-19. Methods: We retrospectively reviewed the data of 6 pregnant patients hospitalized for COVID-19 treated with inhaled NO. Nitric Oxide was delivered at 160- 200 ppm for 30 minutes twice daily until resolution of respiratory symptoms or negative RT-PCR for SARS-CoV- 2. Demographic and clinical data were collected to assess cardiopulmonary function and safety during the treatment. For safety, we focused on the values of blood methemoglobin (MetHb) and inhaled Nitrogen Dioxide (NO2). Data regarding newborn delivery and health, and 28 days outcomes of mothers and babies were collected. Results: Six pregnant patients were admitted with a severe (2 patients) or critical (4 patients) form of COVID-19 and received inhaled NO therapy between April and June 2020. Two pregnant patients were in the second trimester, while 4 were in the third trimester. A total of 39 treatments were administered. No adverse events were reported relating to NO administration. MetHb peaked at 2.5% (1.95%-3%, safety limit =5%) and inhaled NO2 remained below the safety limit of 2ppm. The patients remained hemodynamically stable;cardiac ultrasound performed in three patients did not detect any rebound pulmonary hypertension after NO interruption. Oxygen saturation improved in hypoxemic patients after the initiation of NO (Figure-1). All patients experienced a reduction in respiratory rate (by a median 4.5breaths/min after NO initiation). Three patients delivered a total of 4 babies (negative for SARS-CoV-2) while the other 3 remained pregnant after hospitalization (gestational age 22-26-33weeks) with normal follow-ups. Five mothers out of 6 tested negative for COVID-19 28 days after hospitalization. Conclusion: Nitric oxide gas at 160-200 ppm was safely administered to pregnant patients with severe-critical COVID-19, improved oxygenation and reduced respiratory rate in all 6 patients. The clinical effectiveness shown suggests inhaled high dose NO as a therapeutic novel therapy for COVID-19 in pregnancy.

Ideation and Assessment of a Novel Nitric Oxide Delivery System for Spontaneously Breathing Subjects S. Gianni1

Rationale High dose nitric oxide (NO) produces broad antimicrobial activity and several clinical trials are now testing the efficacy of NO inhalation on patients infected by SARS CoV-2. Nitrogen dioxide (NO2) is formed by the reaction between NO and oxygen, and when combined with water in the airways, NO2, forms nitric acid, leading to a caustic burn of the airways. In this study, we designed and developed a breathing system capable of safely delivering high concentrations of NO. Methods We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide (Ca(OH)2) (Fig. 1). The system was tested using a bench testing lung and a mechanical ventilator. The NO concentration was measured by a NO analyzer connected to the inspiratory limb via a sampling line. NO2 levels were simultaneously evaluated by the Cavity Attenuated Phase Shift (CAPS) NO2 monitor using the same sampling port. To assess the efficacy of the Ca(OH)2 scavenger in reducing the inspiratory levels of NO2, we used a range of target NO concentrations (50, 150, and 250 ppm), two different levels of FiO2 (0.21 and 0.40) and measured NO2 levels with and without the scavenger. We administered high-dose NO with our system to healthy adult volunteers as part of a trial conducted at MGH. Each administration lasted for 15 minutes. Peripheral oxygen saturation (SpO2) and methemoglobin (MetHb) were continuously monitored with a pulse co-oximeter. Results Using our delivery system, we were able to reach NO concentration up 250 ppm with an Inspired oxygen fraction (FiO2) between 0.21 and 0.4. The scavenger reduced the inhaled NO2 concentration to an average of 0.9 ppm (CI -1.58, -0.22;p=0.01). At 150 ppm of inhaled NO, the NO2 concentration was maintained below 1.2 ppm with FiO2 from 0.21 to 0.40. Our data suggest that the scavenger can efficiently reduce NO2 in the circuit for NO delivery. We administered NO to 4 adult volunteers. The total number of NO administrations was 30. The average concentration of inspired NO was 163.9±10.1 ppm with NO2 levels of 0.75±0.08 ppm. During the administration methemoglobin levels increased from a baseline value of 0.97±0.6% to 2.17±0.43%. The subjects did not experience any adverse events. Conclusions We built a NO delivery system that provides a safe alternative to a ventilator-based system to give high dose NO to spontaneously breathing patients.

THE IMPACT OF SOCIAL MEDIA ON COLLEGE STUDENTS DURING COVID-19 PANDEMIC

During the closure of faculties, students are victimisation social media to continue their learning further on recognize additional data concerning the COVID-19 eruption. Social media features a main role in speedily spreading of panic concerning the COVID-19 pandemic among students within the Gaza. In response to reports of individuals experiencing variable levels of tension and depression throughout the eruption of COVID-19, researchers have argued that exposure to connected data on social media could be a salient tributary issue. supported the integrated model of contemplative response vogue and therefore the diathesis-stress model, it's been prompt that incorporating rumination and heedfulness could elucidate the potential mechanism underlying the aforesaid association. This study aimed to look at the mediating role of rumination and therefore the palliative role of heedfulness within the association between social media exposure to COVID-19 data and psychological distress. The results from on-line form responses of 439 school students from 2 universities in urban center, Hubei Province, showed that rumination mediate the association between SME and psychological distress. what is more, heedfulness was discovered as a protecting issue that buffered the adverse result of SME on psychological distress through rumination. These findings advance a far better understanding of the formation method of psychological symptoms throughout the COVID-19 pandemic and supply insights relating to effective interventions for adverse mental state consequences in school students.