The impact of sofosbuvir/daclatasvir or ribavirin in patients with severe COVID-19

• Published in: Journal of antimicrobial chemotherapy Vol. 75; no. 11; pp. 3366 - 3372
• Main Authors: Eslami, Gholamali, Mousaviasl, Sajedeh, Radmanesh, Esmat, Jelvay, Saeed, Bitaraf, Saeid, Simmons, Bryony, Wentzel, Hannah, Hill, Andrew, Sadeghi, Anahita, Freeman, James, Salmanzadeh, Shokrollah, Esmaeilian, Hani, Mobarak, Morteza, Tabibi, Ramin, Jafari Kashi, Amir Hosein, Lotfi, Zahra, Talebzadeh, Seyed Mehdi, Wickramatillake, Aseni, Momtazan, Mahboobeh, Hajizadeh Farsani, Majid, Marjani, Sedigheh, Mobarak, Sara
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.11.2020
• Subjects: Adult; Aged; Antiviral Agents - administration & dosage; Betacoronavirus; Coronavirus Infections - drug therapy; Coronavirus Infections - mortality; COVID-19; Drug Therapy, Combination; Female; Humans; Imidazoles - administration & dosage; Male; Middle Aged; Original Research; Pandemics; Pneumonia, Viral - drug therapy; Pneumonia, Viral - mortality; Ribavirin - administration & dosage; SARS-CoV-2; Sofosbuvir - administration & dosage; Treatment Outcome
• DOI: 10.1093/jac/dkaa331
• ISSN: 0305-7453; 1460-2091

Abstract Objectives Sofosbuvir and daclatasvir are direct-acting antivirals highly effective against hepatitis C virus. There is some in silico and in vitro evidence that suggests these agents may also be effective against SARS-CoV-2. This trial evaluated the effectiveness of sofosbuvir in combination with daclatasvir in treating patients with COVID-19. Methods Patients with a positive nasopharyngeal swab for SARS-CoV-2 on RT–PCR or bilateral multi-lobar ground-glass opacity on their chest CT and signs of severe COVID-19 were included. Subjects were divided into two arms with one arm receiving ribavirin and the other receiving sofosbuvir/daclatasvir. All participants also received the recommended national standard treatment which, at that time, was lopinavir/ritonavir and single-dose hydroxychloroquine. The primary endpoint was time from starting the medication until discharge from hospital with secondary endpoints of duration of ICU stay and mortality. Results Sixty-two subjects met the inclusion criteria, with 35 enrolled in the sofosbuvir/daclatasvir arm and 27 in the ribavirin arm. The median duration of stay was 5 days for the sofosbuvir/daclatasvir group and 9 days for the ribavirin group. The mortality in the sofosbuvir/daclatasvir group was 2/35 (6%) and 9/27 (33%) for the ribavirin group. The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17 (95% CI 0.04–0.73, P = 0.02) and the number needed to treat for benefit was 3.6 (95% CI 2.1–12.1, P < 0.01). Conclusions Given these encouraging initial results, and the current lack of treatments proven to decrease mortality in COVID-19, further investigation in larger-scale trials seems warranted.