H2 inhalation therapy in patients with moderate Covid 19 (H2 COVID) : a prospective ascending-dose phase 1 clinical trial (preprint)

Introduction: The Covid-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for Covid-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. Methods: This Phase I study, characterized by an open-label, prospective, monocentric, and single ascending dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3+3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). Results: We concluded that the Maximum Tolerated Duration is at least three days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. Discussion/conclusion: To the best of our knowledge, this phase 1 clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized Covid-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials.

Risk factors of nosocomial Covid-19 in a French university hospital: a case- control study (preprint)

Background: During the Covid-19 pandemic, prevention strategies implemented by hospitals to reduce nosocomial transmission sometimes failed and determining transmission risk factors remains crucial. Our objective was to determine the risk factors of nosocomial Covid-19.Methods: A case-control study was conducted in a French hospital between 09/01/2020 and 01/31/2021. Adult patients hospitalized in medical or surgical units were included. Infants or patients hospitalized in ICU were excluded. Cases were patients with a nosocomial Covid-19 (clinical symptoms and RT-PCR positive for SARS-CoV-2 or RT-PCR positive for SARS-CoV-2 with Ct ≤28 more than five days after admission); controls were patients without infection (RT-PCR negative for SARS-CoV-2 more than 5 days after admission). They were matched according to length of stay before diagnosis and period of admission. Analyses were performed with a conditional logistic regression.Results: A total of 281 cases and 441 controls were included. In the bivariate analysis, cases were older (OR per 10 years: 1.22; CI95% [1.10; 1.36]), had more often shared a room (OR: 1.74; CI95% [1.25; 2.43]), had more often a risk factor of severe Covid-19 (OR: 1.94; CI95% [1.09; 3.45]), were more often hospitalized in medical units [OR: 1.59; CI95% [1.12; 2.25]), had a higher exposure to contagious health care workers (HCW; OR per 1 person.days: 1.12; CI95% [1.08; 1.17]) and contagious patients (OR per 1 person.days: 1.11; CI95% [1.08; 1.14]) than controls. In an adjusted model, risk factors of nosocomial Covid-19 were exposure to contagious HCW (aOR per 1 person.days: 1.08; CI95% [1.03; 1.14]) and exposure to contagious patients (aOR per 1 person.days: 1.10; CI95% [1.07; 1.13]).Conclusions: Exposure to contagious professionals and contagious patients are the main risk factors for nosocomial Covid-19, outweighing all other potential risk factors including the hospitalisation in double room. Prevention strategies need to be adjusted according to these results to decrease the risk of nosocomial COVID-19.Trial registrationStudy ethics approval was obtained retrospectively on 22 December 2021 (CECIC Rhône-Alpes-Auvergne, Clermont-Ferrand, IRB 5891).