Summary of COVID-19 ribavirin studies
1. Huggins et al., Prospective, Double-Blind, Concurrent, Placebo-Controlled Clinical Trial of Intravenous Ribavirin Therapy of Hemorrhagic Fever with Renal Syndrome
229 patient ribavirin for hantavirus early treatment RCT: 74% lower mortality (p=0.04) and 73% lower progression (p=0.01).RCT 242 hospitalized patients with hemorrhagic fever with renal syndrome (HFRS) from Hantaan virus (the first hantavirus isolated) showing significantly lower mortality with intravenous ribavirin treatment. Ribavirin-treated patients had a sevenfold lower risk of death compared to placebo when adjusted for baseline variables. A notable adverse effect was a reversible hemolytic anemia during treatment, with significantly more ribavirin-treated patients reaching hematocrit below 30%, though no patients required withdrawal from the protocol. The study was conducted over two seasons in Hubei Province, China, with some baseline imbalances between treatment groups noted across the two seasons. Authors hypothesize the primary mechanism of benefit is reduction of viral replication, thereby preventing oliguria and subsequent organ damage. The mean duration of fever at the time of enrollment was 3.7 days during the 1985-1986 season, and 4.3 days during the 1986-1987 season. About 90% of..
Nov 1991, J. Infectious Diseases, https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/164.6.1119, https://c19p.org/huggins
2. Malinin et al., Insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by Puumala virus
73 patient ribavirin for hantavirus early treatment RCT: 15% slower viral clearance (p=0.11).RCT 73 hospitalized patients showing no significant differences with intravenous ribavirin for treatment of haemorrhagic fever with renal syndrome (HFRS) caused by Puumala virus (PUUV). Puumala virus is relatively mild compared to other hantaviruses like Andes and there were no deaths, and only one patient in the control group required RRT. Authors hypothesize that the lack of efficacy may be due to late initiation of therapy, the fact that PUUV disease severity is not strongly correlated with viral load (unlike Hantaan virus). Authors do not report the baseline disease phase for patients. A secondary outcome compares patients in the oliguric phase, but authors do not report how many patients started or entered this phase.
Mar 2017, Infectious Diseases, https://www.tandfonline.com/doi/full/10.1080/23744235.2017.1293841, https://c19p.org/malinin
3. Mertz et al., Placebo-Controlled, Double-Blind Trial of Intravenous Ribavirin for the Treatment of Hantavirus Cardiopulmonary Syndrome in North America
23 patient ribavirin for hantavirus late treatment RCT: 30% higher mortality (p=1) and 22% lower progression (p=1).RCT 36 patients (23 with confirmed hantavirus cardiopulmonary syndrome, HCPS) showing no significant differences with intravenous ribavirin treatment. Mortality and the proportion of patients surviving without extracorporeal membrane oxygenation was similar between groups. Two ribavirin recipients and two placebo recipients died. All patients were enrolled late in the cardiopulmonary phase. Major limitations include the very small sample size (far below the target of 130), inability to enroll any patients during the prodrome phase, and the rapid disease progression once the cardiopulmonary phase began (median time to death or ECMO initiation was only 4 hours after drug initiation in ribavirin recipients), which may have precluded any therapeutic benefit. Authors hypothesize that ribavirin is likely ineffective in the cardiopulmonary stage due to the rapid rate of disease progression compared to hemorrhagic fever with renal syndrome, where ribavirin showed benefit.
Oct 2004, Clinical Infectious Diseases, https://academic.oup.com/cid/article-lookup/doi/10.1086/425007, https://c19p.org/mertz