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Oxford University Press - PMC COVID-19 Collection logoLink to Oxford University Press - PMC COVID-19 Collection
. 2020 Sep 21:ciaa1417. doi: 10.1093/cid/ciaa1417

Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide -- a Single-Center, Randomized, Controlled Clinical Trial

Mengmei Wang 1,#, Yang Zhao 1,#, Weihua Hu 1,#, Dong Zhao 1, Yunting Zhang 1, Tao Wang 1, Zhishui Zheng 1, Xiaochen Li 1, Shaolin Zeng 1, Zhenlian Liu 2, Li Lu 2, Zhihui Wan 2, Ke Hu 1,
PMCID: PMC7543328  PMID: 32955081

Abstract

Objective

To evaluate the efficacy and safety of leflunomide, an approved dihydroorotate dehydrogenase inhibitor, to treat COVID-19 patients with prolonged post-symptomatic viral shedding.

Methods

We conducted a prospective, randomized, controlled, open-label trial involving hospitalized adult COVID-19 patients with prolonged PCR positivity. Patients were randomly assigned to receive either leflunomide (50 mg, q12h, three 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 end point 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 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 RT-PCR, 0.70; 95% confidence interval, 0.391-1.256; P=0.186). In addition, the patients given leflunomide did not have a substantially shorter length of hospital stay than patients treated with interferon alone, with median (IQRs) durations of 29.0 (19.3-47.3) days and 33.0 (29.3-42.8) days, respectively, P=0.170. 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.

Keywords: COVID-19, SARS-CoV-2, leflunomide, interferon alpha 2a, viral shedding


Articles from Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America are provided here courtesy of Oxford University Press

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