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Ribavirin Therapy Associated with Worse Outcome in SARS

By Luciana L. Borio, M.D., July 18, 2005

In a study recently reported in Chest [1],Taiwanese researchers report that patients with confirmed SARS who were treated with ribavirin had worse outcomes as compared with infected patients who did not receive ribavirin.

Ribavirin, a broad-spectrum antiviral with activity against DNA and RNA viruses, is licensed for treatment of severe respiratory syncitial virus infection in infants and chronic hepatitis C virus infection (in combination with interferon). Ribavirin may also have a role in the treatment of a number of hemorrhagic fever viruses [2]. During the SARS outbreak in 2003, several hospitals devised treatment protocols that included ribavirin because there were no known effective therapies against the novel coronavirus. Ribavirin is associated with several adverse side effects, the most common of which is a reversible, dose and time-dependent anemia.

The authors analyzed outcomes for 51 patients with confirmed SARS in a retrospective, observational study. The patients were managed in one of two medical centers in Taiwan between April 24 and June 30, 2003, during which time the Taiwan Centers for Disease Control and Prevention devised a treatment protocol that included ribavirin. Forty-four patients treated at Mackay Memorial Hospital received ribavirin; 7 patients treated at Chang Gung Memorial Hospital did not. The authors state that no particular bias could be ascertained between the two hospital groups since patients were randomly assigned to receive care at designated hospitals by public health authorities, and the treatment protocols were otherwise the same. Both groups were treated with cephalosporins and fluoroquinolones upon presentation; corticosteroids were given if they failed to improve clinically after a specified amount of time.

Patients who took ribavirin experienced a higher frequency of adverse events: 32 of 44 (73%) developed anemia, and 17 of 44 (39%) developed hypoxemia. Of the seven patients who did not take ribavirin, one (14%) developed anemia and one other developed hypoxemia (14%). The authors note that anemia was also observed in nine of 19 (47%) patients outside of this cohort who received ribavirin but were subsequently excluded from having SARS, suggesting ribavirin as a strong contributor to the development of anemia (and not the SARS virus itself). In addition, mortality was higher in the ribavirin group, but this was not statistically significant. Mortality was highest (29%) in hypoxemic, anemic patients. On multivariate analysis, only hemoglobin level was significantly correlated with hypoxemia or death.

The use of ribavirin was likely justified during the SARS outbreak in the absence of any known effective therapy and anecdotal reports. Since the SARS outbreak in 2003, a number of studies have reported adverse effects associated with ribavirin therapy [3,4]. This small study adds to the existing data and suggests that ribavirin use is associated with a poorer outcome and should not be used should SARS reemerge.

References

  1. Chiou HE, Liu CL, Buttrey MJ, et al. Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers. Chest. Jul 2005;128(1):263-272.

  2. Borio L, Inglesby T, Peters CJ, et al. Hemorrhagic fever viruses as biological weapons: medical and public health management. JAMA. May 8 2002;287(18):2391-2405.

  3. Booth CM, Matukas LM, Tomlinson GA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. Jun 4 2003;289(21):2801-2809.

  4. Fujii T, Nakamura T, Iwamoto A. Current concepts in SARS treatment. J Infect Chemother. Feb 2004;10(1):1-7.