Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea (difficulty breathing) in patients with Coronavirus disease


Coronavirus disease 2019 (COVID-19) has resulted in more than 8.7 million laboratory-confirmed cases and 0.46 million deaths globally (1). Few therapies, if any, have been shown to rapidly ameliorate the respiratory symptoms and prevent against the disease progression. An important mechanism contributing to dyspnea and disease progression in patients with COVID-19 might be the increased work of breathing because of the heightened airway resistance (2). Inhalation of hydrogen/oxygen mixed gas (H2-O2) might have a role in the treatment of COVID-19 given the decreased resistance compared with room air when passing through the airways.

Recently, we conducted an open-label multicenter clinical trial, between January 21st and March 23rd, 2020, among patients with laboratory-confirmed COVID-19 from seven hospitals in China. The patients were aged 18–85 years, and had dyspnea both on hospital admission and at enrollment [See Online Supplement (http://dx.doi.org/10.21037/jtd-2020-057) for patient sources, inclusion/exclusion criteria and outcome measures].

H2-O2 inhalation resulted in significantly more patients with improved disease severity at day 2 (20.5% vs. 2.3%, P=0.019; RR: 9.0, 95% CI: 1.2–68.1) and 3 (31.8% vs. 11.5%, P=0.038; RR: 2.8, 95% CI: 1.1–7.1) and end-of-treatment (70.5% vs. 31.8%, P<0.001; RR: 2.2, 95% CI: 1.4–3.6) (Figure 1). The improvement of dyspnea scale (50.0% vs. 23.9%, P=0.019; RR: 2.1, 95% CI: 1.2–3.8) was greater in H2-O2treatment group at day 2. H2-O2 inhalation improved chest distress and chest pain (all P<0.05). The improvement in cough scale was greater in treatment group at days 2 and 3 (both P<0.05). Furthermore, the improvement in resting oxygen saturation was greater after H2-O2 inhalation (all P<0.05, Table 1).

On the basis of standard-of-care (3), patients in treatment group inhaled H2-O2 (66% hydrogen; 33% oxygen) at 6 L/min via nasal cannula by using the Hydrogen/Oxygen Generator (model AMS-H-03, Shanghai Asclepius Meditec Co., Ltd., China) daily until discharge [see Figure E1 in Online Supplement (http://dx.doi.org/10.21037/jtd-2020-057)]. Patients in control group received standard-of-care (with oxygen therapy each day) alone until discharge. Clinical assessments included the five-category ordinal scale [see Panel 1 in Online Supplement (http://dx.doi.org/10.21037/jtd-2020-057)], four-category ordinary scale of dyspnea, coughing, chest distress and chest pain (0: None; 1: Mild; 2: Moderate; 3: Severe; 4: Very severe) and adverse events, performed on admission, at enrollment, at days 2 and 3, and the day before discharge (end-of-treatment). The primary endpoint was the proportion of patients with improved disease severity (by at least one scale). Secondary endpoints comprised the change from baseline in oxygen saturation and symptom scales.

Treated Group (44 subjects) versus Control Group (46 subjects)

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