Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76–2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, time to defervescence was 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95%CI, 0.81–4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by RT-PCR by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred to any of the patients in either treatment group during the 28-day participation (Japan Registry of Clinical Trials jRCTs041190120).

The novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, has spread worldwide from China. There are no case reports from Asia of COVID-19 with facial paralysis and olfactory disturbance. We herein report a case of COVID-19 pneumonia in a Japanese woman who showed facial nerve palsy and olfactory disturbance.

The incubation period of the SARS-CoV-2 B1.1.7 variant is shorter than that of other strains Dear editorWe read with great interest, the article by Yumeng Gao et al., who reported that SARS-CoV-2 was contagious during the incubation period, with a median incubation period of 10 days. 1 However, no studies have so far reported the incubation period of the B.1.1.7 variant that was reported to have a substantial transmission advantage over other lineages. 2 Here, we report that the incubation period of the B.1.1.7 variant is shorter than other strains.In mid-March 2021, a cluster of B.1.1.7 variant cases occurred in downtown Matsuyama, Ehime Prefecture, Japan with approximately 200 positive cases reported as of March 31. As patients infected with the B.1.1.7 variant were hospitalized for isolation under national regulations, we were able to obtain a detailed medical history; most were infected in restaurants and bars open late at night. The medical histories imply that the incubation period of the B.1.1.7 variant may be shorter than that of other strains. Since February 2020, a retrospective investigation at a public health center in Japan reported a high risk of clusters occurring in '3C' environments (closed spaces, crowded places, and close-contact settings). 3 In this study, the main sites of infection were bars and late-night restaurants, which are 3C environments. Therefore, we also investigated the effect of 3C environments on the incubation periods of the B.1.1.7 variant and other strains.This retrospective observational study enrolled patients with symptomatic novel coronavirus infection admitted to either of two medical institutions in Ehime Prefecture, Japan. The study included patients admitted in March 2021 with novel coronavirus infections caused by the B.1.1.7 variant and patients infected with other SARS-CoV-2 strains admitted between March 1, 2020 and January 31, 2021. The B.1.1.7 variant was detected by real-time PCR tests for the N501Y mutation, 4 and confirmed by the whole-genome sequences of the strain. 5 The study included only patients whose age, sex, source of infection, date of exposure, and date of onset were clearly documented. In March 2021, 57 patients infected with the B.1.1.7 variant were admitted. Of these, 27 were excluded because of missing data, such as unknown source or date of exposure, and the remaining 30 were included in the study ( Fig. 1 A). There were 149 patients infected with other strains admitted between March 1, 2020 and January 31, 2021. Of these, 107 were excluded because of missing data such as unknown source or date of exposure, indeterminable or asymptomatic cases, or inability to communicate; the remaining 42 patients were included ( Fig. 1 B). Of the 30 and 42 patients infected with the B.1.1.7 variant and other strains, respectively, 28 and 20 were infected in 3C environments, respectively.Poisson regression analysis was used to examine the relationship between the incubation period of the B.1.1.7 variant and those

Previous studies have reported that a high neutrophil-to-lymphocyte ratio (NLR) is associated with disease severity and poor prognosis in COVID-19 patients. We aimed to investigate the clinical implications of NLR in patients with COVID-19 complicated with cardiovascular diseases and/or its risk factors (CVDRF). In total, 601 patients with known NLR values were selected from the CLAVIS-COVID registry for analysis. Patients were categorized into quartiles (Q1, Q2, Q3, and Q4) according to baseline NLR values, and demographic and clinical parameters were compared between the groups. Survival analysis was conducted using the Kaplan–Meier method. The diagnostic performance of the baseline and follow-up NLR values was tested using receiver operating characteristic (ROC) curve analysis. Finally, two-dimensional mapping of patient characteristics was conducted using t-stochastic neighborhood embedding (t-SNE). In-hospital mortality significantly increased with an increase in the baseline NLR quartile (Q1 6.3%, Q2 11.0%, Q3 20.5%; and Q4, 26.6%; p < 0.001). The cumulative mortality increased as the quartile of the baseline NLR increased. The paired log-rank test revealed significant differences in survival for Q1 vs. Q3 (p = 0.017), Q1 vs. Q4 (p < 0.001), Q2 vs. Q3 (p = 0.034), and Q2 vs. Q4 (p < 0.001). However, baseline NLR was not identified as an independent prognostic factor using a multivariate Cox proportional hazards regression model. The area under the curve for predicting in-hospital death based on baseline NLR was only 0.682, whereas that of follow-up NLR was 0.893. The two-dimensional patient map with t-SNE showed a cluster characterized by high mortality with high NLR at follow-up, but these did not necessarily overlap with the population with high NLR at baseline. NLR may have prognostic implications in hospitalized COVID-19 patients with CVDRF, but its significance depends on the timing of data collection.

Keywords： anticoagulation, antiplatelet，COVID19, dialysis patients, retroperitoneal hemorrhage 〈Abstract〉 A 73 year old male had started undergoing hemodialysis due to diabetic nephropathy seven years ago. He was receiving dual antiplatelet therapy, as he had undergone coronary stenting. He was diagnosed with novel coronavirus disease 2019 (COVID 19) by contact screening and admitted to our hospital. Chest CT only showed a single ground glass opacity； however, prophylactic heparin treatment was started because his D dimer level was slightly elevated. Dexamethasone was started on the 4th day of hospitalization, as the patient had had a fever