The Assessment of the Efficacy and Safety of Favipiravir for Patients with SARS-CoV-2 Infection: A Multicenter Non-randomized, Uncontrolled Single-arm Prospective Study.

Objective Among treatment options for coronavirus infectious disease 2019 (COVID-19), well-studied oral medications are limited. We conducted a multicenter non-randomized, uncontrolled single-arm prospective study to assess the efficacy and safety of favipiravir for patients with COVID-19. Methods One hundred participants were sequentially recruited to 2 cohorts: cohort 1 (Day 1: 1,600 mg/day, Day 2 to 14: 600 mg/day, n=50) and cohort 2 (Day 1: 1,800 mg/day, Day 2 to 14: 800 mg/day, n=50). The efficacy endpoint was the negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the odds ratio (OR) of cohort 2 to cohort 1 for negative conversion on Day 10 was calculated. Characteristics of all participants and profiles of adverse events (AEs) were collected and analyzed. Results The mean age of participants was 62.8±17.6 years old. Thirty-four patients (34.0%) experienced worsening pneumonia, 7 (7.0%) were intubated, and 4 (4.0%) died during the observation period. Cohort 2 showed a higher negative conversion rate than cohort 1 [adjusted OR 3.32 (95% confidence interval (CI), 1.17 to 9.38), p=0.024], and this association was maintained after adjusting for the age, sex, body mass index, and baseline C-reactive protein level. Regarding adverse events, hyperuricemia was most frequently observed followed by an elevation of the liver enzyme levels (all-grade: 49.0%, Grade ≥3: 12.0%), and cohort 2 tended to have a higher incidence than cohort 1. However, no remarkable association of adverse events was observed between patients <65 and ≥65 years old. Conclusion The antiviral efficacy of favipiravir was difficult to interpret due to the limitation of the study design. However, no remarkable issues with safety or tolerability associated with favipiravir were observed, even in elderly patients with COVID-19.

Relation of Sex Hormone Levels With Prevalent and 10-Year Change in Aortic Distensibility Assessed by MRI: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Women experience a steeper decline in aortic elasticity related to aging compared to men. We examined whether sex hormone levels were associated with ascending aortic distensibility (AAD) in the Multi-Ethnic Study of Atherosclerosis. METHODS: We studied 1,345 postmenopausal women and 1,532 men aged 45-84 years, who had serum sex hormone levels, AAD measured by phase-contrast cardiac magnetic resonance imaging, and ejection fraction>50% at baseline. Among these participants, 457 women and 548 men returned for follow-up magnetic resonance imaging 10-years later. Stratified by sex, and using mixed effects linear regression methods, we examined associations of sex hormones (as tertiles) with baseline and annual change in log-transformed AAD (mm Hg-110-3), adjusting for demographics, body size, lifestyle factors, mean arterial pressure, heart rate, hypertensive medication use (and in women, for hormone therapy use and years since menopause). RESULTS: The mean (SD) age was 65 (9) for women and 62 (10) years for men. AAD was lower in women than men (P < 0.001). In adjusted cross-sectional analysis, the highest tertile of free testosterone (compared to lowest) in women was significantly associated with lower AAD [-0.10 (-0.19, -0.01)] and the highest tertile of estradiol in men was associated with greater AAD [0.12 (0.04, 0.20)]. There were no associations of sex hormones with change in AAD over 10 years, albeit in a smaller sample size. CONCLUSIONS: Lower free testosterone in women and higher estradiol in men were associated with greater aortic distensibility at baseline, but not longitudinally. Sex hormone levels may account for differences in AAD between women and men.