A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

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 (in the latter case, 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 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

Retroperitoneal Hemorrhage in Patients with COVID-19 Undergoing Hemodialysis: Three Case Reports.

A 73-year-old man receiving hemodialysis and antiplatelets was admitted with a mild case of COVID-19. Heparin was added, and iliopsoas hemorrhage developed. He was successfully treated by interventional radiology. A 76-year-old man receiving hemodialysis and antiplatelets was admitted with mild COVID-19. Heparin was added, and iliacus hemorrhage developed. Despite heparin discontinuation, he died of worsening pneumonia. A 74-year-old man undergoing hemodialysis was admitted with severe COVID-19. Gastrointestinal bleeding developed during continuous hemodiafiltration with heparin. Upon switching to nafamostat and increasing the dose, iliopsoas hemorrhage developed. Despite interventional radiology, he died of infectious complications. Attention to hemorrhagic complications is therefore needed in patients with COVID-19.

Predictive value of neutrophil-to-lymphocyte ratio for the fatality of COVID-19 patients complicated with cardiovascular diseases and/or risk factors.

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.

Coronavirus Disease-19 Pneumonia with Facial Nerve Palsy and Olfactory Disturbance.

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.