Molecular hydrogen for outpatients with Covid-19 (Hydro-Covid): a phase 3, randomised, triple-blinded, adaptive, placebo-controlled, multicentre trial (preprint)

Background: Due to its antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties, molecular hydrogen (H2) is potentially a novel therapeutic gas for acute coronavirus disease 2019 (COVID-19) patients. Aim To determine the efficacy and safety profile of hydrogen rich water (HRW) to reduce the risk of progression of COVID-19. Design and settings We conducted a phase 3, triple-blind, randomized, placebo-controlled trial to evaluate treatment with HRW started within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19 and at least one risk factor for severe COVID-19 illness. Method Participants were randomly assigned to receive HRW or placebo twice daily for 21 days. The composite primary endpoint was the incidence of clinical worsening (dyspnea, fatigue) associated with a need for oxygen therapy, hospitalization or death at day-14; the incidence of adverse events was the primary safety end point. Results A total of 675 participants were followed up until day-30. 337 in the HRW group and 338 in the placebo group. Baseline characteristics were similar in the two groups. HRW was not superior to placebo in preventing clinical worsening at day-14: in H2 group, 46.1% met a clinical deterioration, 43.5% in the placebo group, Hazard Ratio 1.09, 90% confidence interval [0.90-1.31]. One death was reported in the H2 group and 2 in the placebo group at day-30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants respectively. Conclusion Twice-daily ingestion of HRW from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening. Keywords: COVID-19; Molecular Hydrogen; Administration, Oral; Primary health care; Outcome Assessment;

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). 

Fine analysis of lymphocyte subpopulations in SARS-CoV-2 infected patients: toward a differential profiling of patients with severe outcome (preprint)

COVID-19 is caused by the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in widespread morbidity and mortality. CD4+ T cells, CD8+ T cells and neutralizing antibodies all contribute to control SARS-CoV-2 infection. However, heterogeneity is a major factor in disease severity and in immune innate and adaptive responses to SARS-CoV-2. We performed a deep analysis by flow cytometry of lymphocyte populations of 125 hospitalized SARS-CoV-2 infected patients on the day of hospital admission. Five clusters of patients were identified using hierarchical classification on the basis of their immunophenotypic profile, with different mortality outcomes. Some characteristics were observed in all the clusters of patients, such as lymphopenia and an elevated level of effector CD8+CCR7- T cells. However, low levels of T cell activation are associated to a better disease outcome; on the other hand, profound CD8+ T-cell lymphopenia, a high level of CD4+ and CD8+ T-cell activation and a high level of CD8+ T-cell senescence are associated with a higher mortality outcome. Furthermore, a cluster of patient was characterized by high B-cell responses with an extremely high level of plasmablasts. Our study points out the prognostic value of lymphocyte parameters such as T-cell activation and senescence and strengthen the interest in treating the patients early in course of the disease with targeted immunomodulatory therapies based on the type of adaptive response of each patient.