Ribavirin

Last review completed on
April 19th, 2020

Activity of ribavirin against SARS-CoV-2 has been demostrated in vitro (Wang 2020), although it was found to be 100-fold less potent than remdesivir and chloroquine. This may suggest the challenge of narrow therapeutic window for ribavirin. A mouse study (Barnard 2006) of SARS-CoV-1 had demonstrated higher levels of virus in lungs in those treated with ribavirin compared to no treatment. Treatment with interferon-α2b and ribavirin in macaques infected with MERS-CoV (Falzarano 2013) showed benefit of this combination. Combination of LPV/r and ritonavir demonstrated synergy in vitro against SARS-CoV-1 and clinical benefit in patients treated with combination compare to ribavirin alone in historical controls (Chu 2004). Review (Stockman 2006) reported most human clinical studies were inconclusive and some showed harm of ribavirin in treating SARS-CoV-1. Largest study (retrospective cohort) in critically ill patients with MERS (Arabi 2019) showed no difference in mortality or viral clearance in those treated with combination ribavirin and interferon. There is insufficient evidence to support use of ribavirin for treatment of patients infected with SARS-CoV-2. Current studies of ribavirin in SARS-CoV-2 involve combination with interferon and LPV/r.

Recommendation

There is insufficient evidence to support use of ribavirin for treatment of patients infected with SARS-CoV-2. There are several studies under way to evaluate the use of ribavirin in combination with other agents for treatment of SARS-CoV-2.

Level of Evidence
= Supporting use article = Neutral Article  = Contradicting use article

Step 1 - In vitro SARS CoV-1/2 and MERS-CoV
 Step 2 - In vivo MERS-CoV
Supporting Use article		 Step 3 - In vivo SARS CoV-2

Major Peer-reviewed Studies

Level 1: In vitro SARS CoV-1/2 and MERS-CoV articles listed below In vitro SARS CoV-2
  1. Supporting Use article Wang et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research 2020;30:269-71. Ribavirin active but 100-fold less potent than remdesivir and chloroquine. (preclinical)
Level 2: In vivo SARS CoV-1/MERS articles listed below In vivo SARS CoV-1/MERS
  1. Contradicting Use article Barnard DL et al. Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin. Antiviral Res. 2006 Aug;71(1):53-63. (preclinical)
  2. Supporting Use article Falzarano D et al. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med. 2013 Oct;19(10):1313-1317. Benefit to those treated with combination in breathing, lung findings, inflammation compared to untreated. (preclinical, MERS)
Human Studies and SARS CoV-1/MERS
  1. Chu CM et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59:252–256. In vitro testing showed synergy of LPV/r and ribavirin, and this combination showed benefit compared to historical controls treated with ribavirin alone. (preclinical and human study, SARS-CoV-1)
  2. Chiou H, et al. Adverse effects of ribavirin and outcome in SARS. Chest. 2005;128:263-272. Retrospective study shows high rate of anemia and hypoxia in patients on ribavirin, no clinical benefit. (human study, SARS-CoV-1)
  3. Contradicting Use article Arabi et al. Ribavirin and Interferon Therapy for Critically Ill Patient With Middle East Respiratory Syndrome: A Multicenter Observational Study. Clin Infect Dis. 2020 Apr 15;70(9):1837-44. No difference in mortality or viral clearance. (human study, MERS)
Review of Studies with SARS CoV-1
  1. Contradicting Use article Stockman LJ et al. SARS: Systematic Review of Treatment Effects. PLoS Med. 2006 Sep;3(9):e343. Reviews data on ribavirin — mostly inconclusive, some studies show harm. (review, SARS-CoV-1)
Antiviral