ABSTRACT
Background: In vitro drug-screening studies have indicated that camostat mesilate (FOY-305) may prevent SARS-CoV-2 infection into human airway epithelial cells. This study was conducted to investigate whether camostat mesilate is an effective treatment for SARS-CoV-2 infection (COVID-19). Methods: This was a phase 3, multicentre, double-blind, randomised, parallel-group, placebo-controlled study. Patients were enrolled if they were admitted to a hospital within 5 days of onset of COVID-19 symptoms or within 5 days of a positive test for asymptomatic patients. Severe cases (e.g., those requiring oxygenation/ventilation) were excluded. Patients were administered camostat mesilate (600 mg qid; four to eight times higher than the clinical doses in Japan) or placebo for up to 14 days. The primary efficacy endpoint was the time to the first two consecutive negative tests for SARS-CoV-2. Findings: One-hundred and fifty-five patients were randomised to receive camostat mesilate (n=78) or placebo (n=77). The median time to the first test was 11 days in both groups, and conversion to negative status was observed in 60.8% and 63.5% of patients in the camostat mesilate and placebo groups, respectively. The primary (Bayesian) and secondary (frequentist) analyses found no significant differences in the primary endpoint between the two groups. No additional safety concerns beyond those already known for camostat mesilate were identified. Interpretation: Camostat mesilate is no more effective, based on upper airway viral clearance, than placebo for treating patients with mild to moderate SARS-CoV-2 infection with or without symptoms. Funding: Ono Pharmaceutical Co., Ltd.
Subject(s)
COVID-19ABSTRACT
Background: The risk of SARS-CoV-2 infection when people handle the linens used by coronavirus disease (COVID-19) patients is uncertain. We examined the risk of SARS-CoV-2 infection among workers who change and wash the linens contaminated by SARS-CoV-2.Methods: This was a randomized controlled trial. Participants at a hospital and an accommodation facility who tested positive for SARS-CoV-2 were registered from September 16 to November 19, 2020. One of five washing (water, detergent, or softener) and disinfection (80℃ 10 min or 250 ppm sodium hypochlorite) methods was assigned to each facility on each washing day (the day of admission (day 1) and day 3) using static simple randomization. Samples before and after washing/disinfection were tested for RT-PCR and virus isolation on day 1 and day 3. The air in the workspace and the personal protective equipment worn by linen-handling people were also tested on days 1, 3, 5 and 7.Findings: Among 700 samples from 13 COVID-19 participants and their surrounding environment, SARS-CoV-2 RNA was detected from 14% (52/362) of the linens used by COVID-19 patients (cycle threshold (Ct) value:33-40). After washing or disinfection, SARS-CoV-2 RNA was detected from samples washed by laundry detergent or fabric softener with high Ct values (>36). SARS-CoV-2 RNA was also detected with high Ct values (>36) from 10% of gowns from people who handled used linens (5/52) but not from goggles nor N95 masks, and from 15% of air samples in the rooms where linens were retrieved (16/104). No SARS-CoV-2 was isolated from any samples.Interpretation: The risk of SARS-CoV-2 infection in handling linens used by COVID-19 patients exists but seems to be low and the contaminated linens were safe after washing by laundry detergent.Funding: This study was supported by the grant from Ministry of Health, Labour and Welfare (Grant No. 20CA2036).Declaration of Interest: All authors declare that they have no conflict of interest.Ethical Approval: This study was approved by the Institutional Review Boards of the National Institute of Infectious Diseases Japan (approval No. 1167) and International University of Health and Welfare (approval No. 20-Nr-066).
Subject(s)
COVID-19 , Coronavirus Infections , Communicable DiseasesABSTRACT
Background: Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score–matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease.Methods: This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January–April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15.Results: Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388–0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323–2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841–2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347–5.950; p = 0.006).Conclusions: Corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).