Treatment of Coronavirus Disease 2019 Patients With Prolonged Postsymptomatic Viral Shedding With Leflunomide: A Single-center Randomized Controlled Clinical Trial.

BACKGROUND: We aimed to evaluate the efficacy and safety of leflunomide, an approved dihydroorotate dehydrogenase inhibitor, to treat coronavirus disease 2019 (COVID-19) patients with prolonged postsymptomatic viral shedding. METHODS: We conducted a prospective, randomized controlled, open-label trial involving hospitalized adult COVID-19 patients with prolonged polymerase chain reaction (PCR) positivity. Patients were randomly assigned to receive either leflunomide (50 mg every 12 hours, 3 consecutive times, orally; then 20 mg once daily for 8 days), in addition to nebulized interferon alpha 2a (IFN-α-2a, 3 million IU each time, twice daily for 10 days), or nebulized IFN-α-2a alone for 10 days. The primary endpoint was the duration of viral shedding. RESULTS: A total of 50 COVID-19 patients with prolonged PCR positivity were randomized into 2 groups: 26 were assigned to the leflunomide plus IFN-α-2a group, and 24 were assigned to the interferon-alone group. Treatment with leflunomide was not associated with a difference from the interferon-alone group in the duration of viral shedding (hazard ratio for negative reverse-transcription PCR, 0.70 [95% confidence interval, .391-1.256]; P = .186). In addition, the patients given leflunomide did not have a substantially shorter length of hospital stay than patients treated with interferon alone, with median durations of 29.0 (interquartile range [IQR], 19.3-47.3) days and 33.0 (IQR, 29.3-42.8) days, respectively (P = .170). Two leflunomide recipients were unable to complete the full 10-day course of administration due to adverse events. CONCLUSIONS: In COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN-α-2a beyond IFN-α-2a alone.

Clinical Courses and Outcomes of Patients with Chronic Obstructive Pulmonary Disease During the COVID-19 Epidemic in Hubei, China.

Purpose: In this study, we investigated the acute exacerbation and outcomes of COPD patients during the outbreak of COVID-19 and evaluated the prevalence and mortality of COPD patients with confirmed COVID-19. Methods: A prospectively recruited cohort of 489 COPD patients was retrospectively followed-up for their conditions during the COVID-19 pandemic from December 2019 to March 2020 in Hubei, China. In addition, the features of 821 discharged patients with confirmed COVID-19 were retrospectively analyzed. Results: Of the 489 followed-up enrolled COPD patients, 2 cases were diagnosed as confirmed COVID-19, and 97 cases had exacerbations, 32 cases of which were hospitalized, and 14 cases died. Compared with the 6-month follow-up results collected 1 year ago, in 307 cases of this cohort, the rates of exacerbations and hospitalization of the 489 COPD patients during the last 4 months decreased, while the mortality rate increased significantly (2.86% vs 0.65%, p=0.023). Of the 821 patients with COVID-19, 37 cases (4.5%) had pre-existing COPD. Of 180 confirmed deaths, 19 cases (10.6%) were combined with COPD. Compared to COVID-19 deaths without COPD, COVID-19 deaths with COPD had higher rates of coronary artery disease and/or cerebrovascular diseases. Old age, low BMI and low parameters of lung function were risk factors of all-cause mortality for COVID-19 patients with pre-existing COPD. Conclusion: Our findings imply that acute exacerbations and hospitalizations of COPD patients were infrequent during the COVID-19 pandemic. However, COVID-19 patients with pre-existing COPD had a higher risk of all-cause mortality.

Resolution of Coronavirus Disease 2019 Infection and Pulmonary Pathology With Nebulized DAS181: A Pilot Study.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 infections commonly lead to respiratory failure and potentially fatal systemic inflammation and organ failure. Nebulized DAS181, a host-directed biologics with sialidase activity, is an investigational drug with antiviral activities on parainfluenza and influenza under phase 3 and phase 2 development. The objective of this study (NCT04324489) is to investigate the safety and effects of nebulized DAS181 on hypoxic coronavirus disease 2019 patients. DESIGN: Single-center, prospective, open-label, compassionate use. SETTING: Renmin Hospital of Wuhan University, Department of Respiratory and Critical Care Medicine and Department of Infectious Diseases. SUBJECTS: Patients 18 to 70 years old who met Chinese criteria for severe coronavirus disease 2019 pneumonia and required supplemental oxygen but not on mechanical ventilator at screening. INTERVENTIONS: Nebulized DAS181 (4.5 mg) twice a day for 10 days. MEASUREMENTS AND MAIN RESULTS: Three male coronavirus disease 2019 hypoxic patients with bilateral lung involvement completed DAS181 treatment for 10 days. By day 14, all achieved return to room air (primary endpoint) and their nasopharyngeal swabs were negative for severe acute respiratory syndrome coronavirus 2. Clinical severity improved from severe coronavirus disease 2019 at baseline to moderate or mild disease by day 5, consistent with rapid reduction of inflammatory cytokines by days 2-3 and radiologic improvement by days 5-10. No DAS181-related adverse events were reported. CONCLUSIONS: Inhalation of DAS181 was well tolerated and potential clinical benefit of DAS181 on hypoxic coronavirus disease 2019 is the reduction of supplemental oxygen need. Efficacy and safety, including pharmacokinetics and viral studies of DAS181 in severe, hypoxic coronavirus disease 2019, should be examined by a double-blind, randomized controlled study.