Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives.

COVID-19 is a widespread global pandemic with nearly 185 million confirmed cases and about four million deaths. It is caused by an infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which primarily affects the alveolar type II pneumocytes. The infection induces pathological responses including increased inflammation, oxidative stress, and apoptosis. This situation results in impaired gas exchange, hypoxia, and other sequelae that lead to multisystem organ failure and death. As summarized in this article, many interventions and therapeutics have been proposed and investigated to combat the viral infection-induced inflammation and oxidative stress that contributes to the etiology and pathogenesis of COVID-19. However, these methods have not significantly improved treatment outcomes. This may partly be attributable to their inability at restoring redox and inflammatory homeostasis, for which molecular hydrogen (H2), an emerging novel medical gas, may complement. Herein, we systematically review the antioxidative, anti-inflammatory, and antiapoptotic mechanisms of H2. Its small molecular size and nonpolarity allow H2 to rapidly diffuse through cell membranes and penetrate cellular organelles. H2 has been demonstrated to suppress NF-κB inflammatory signaling and induce the Nrf2/Keap1 antioxidant pathway, as well as to improve mitochondrial function and enhance cellular bioenergetics. Many preclinical and clinical studies have demonstrated the beneficial effects of H2 in varying diseases, including COVID-19. However, the exact mechanisms, primary modes of action, and its true clinical effects remain to be delineated and verified. Accordingly, additional mechanistic and clinical research into this novel medical gas to combat COVID-19 complications is warranted.

Covalent Antiviral Agents.

Nowadays, many viral infections have emerged and are taking a huge toll on human lives globally. Meanwhile, viral resistance to current drugs has drastically increased. Hence, there is a pressing need to design potent broad-spectrum antiviral agents to treat a variety of viral infections and overcome viral resistance. Covalent inhibitors have the potential to achieve both goals owing to their biochemical efficiency, prolonged duration of action, and the capability to inhibit shallow, solvent-exposed substrate-binding domains. In this chapter, we review the structures, activities, and inhibition mechanisms of covalent inhibitors against severe acute respiratory syndrome coronavirus 2, dengue virus, enterovirus, hepatitis C virus, human immunodeficiency virus, and influenza viruses. We also discuss the application of in silico study in covalent inhibitor design.

Erratum to "Withdrawal notice to the effectiveness of diaphragmatic breathing relaxation training for improving sleep quality among nursing staff during the COVID-19 outbreak: a before and after study" [Sleep Medicine X (2) (2020) 100026].

[This corrects the article DOI: 10.1016/j.sleepx.2020.100026.].

The effectiveness of diaphragmatic breathing relaxation training for improving sleep quality among nursing staff during the COVID-19 outbreak: a before and after study.

OBJECTIVES: Recent studies have demonstrated that first-line nurses involved in the coronavirus disease-2019 (COVID-19) crisis may experience sleep disturbances. As breathing relaxation techniques can improve sleep quality, anxiety, and depression, the current study aimed to evaluate the effectiveness of diaphragmatic breathing relaxation training (DBRT) for improving sleep quality among nurses in Wuhan, China during the COVID-19 outbreak. METHODS: This study used a quasi-experimental (before and after) intervention strategy, with 151 first-line nurses from four wards in Leishenshan hospital. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) to evaluate the effectiveness of DBRT before and after the intervention. Data were examined using the Shapiro-Wilk test, Levene's test, and paired t-test. RESULTS: A total of 140 nurses completed the DBRT sessions. First-line nurses achieved significant reductions in global sleep quality (p < 0.01), subjective sleep quality (p < 0.001), sleep latency (p < 0.01), sleep duration (p < 0.001), sleep disturbances (p < 0.001), habitual sleep efficiency (p = 0.015), daytime dysfunction (p = 0.001), and anxiety (p = 0.001). There were no significant reductions in the use of sleeping medication (p = 0.134) and depression (p = 0.359). CONCLUSION: DBRT is a useful non-pharmacological treatment for improving sleep quality and reducing anxiety among first-line nurses involved in the COVID-19 outbreak. The study protocol was clinically registered by the Chinese Clinical Trial Registry. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000032743.