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(Chest. 2005;128:4050.)
© 2005 American College of Chest Physicians

Ribavarin Should Be Tested in Clinical Trials in Combination With Other Antiviral Agents for Severe Acute Respiratory Syndrome

Chung-Ming Chu, MD, FCCP and Kin-Sang Chan, MBBS, FCCP

United Christian Hospital, Hong Kong

Correspondence to: Chung-Ming Chu, MD, FCCP, United Christian Hospital, Hong Kong, PRC

To the Editor:

We read with interest the article in CHEST by Chiou et al (July 2005)1 and offer the following comments. The ribavirin-treated patients had higher lactate dehydrogenase levels, a well-known adverse prognostic factor in severe acute respiratory syndrome (SARS). The nonsignificantly higher mortality could be due to the more severe disease in this group. Viral load, another important predictor of mortality, was not available.2 Moreover, Figure 1 seemed inaccurate: the survival in ribavirin-treated patients should be 0.88 at day 30 (5 of 44 patients died) instead of 0.71.

Classifying the ribavirin-treated patients into hypoxemic and nonhypoxemic subgroups (Table 2) and attributing the higher mortality in the hypoxemic subgroup to ribavirin was problematic, as both subgroups were treated with an identical protocol of ribavirin. From the data presented, a more likely explanation for the more severe drop in hemoglobin in the hypoxemic subgroup was that they had more severe disease. The survival curves in Figure 4 also appeared inaccurate: the survival in patients with drop in hemoglobin > 2 g/dL should be 0.69 (5 of 16 patients died) instead of 0.45. Hence, the result of the log-rank test (p = 0.007) needs to be justified.

Only factors that were potentially associated with hypoxemia were analyzed in Table 2. No univariate or multivariate analyses on factors related to death were reported. The conclusion that hemoglobin level was the only factor associated with death was not supported by the data presented.

In Figure 6, the shaded triangles were supposed to represent the hemoglobin of patients who were hypoxemic and had received ribavirin. There were 22 triangles, but there should only be 17 patients. In addition, expressing the survival of individual patients by proportion (y-axis) is difficult to understand.

Therefore, there is no convincing evidence that ribavirin has contributed to a life-threatening drop in hemoglobin or mortality in this report. As of today, three independent studies345 have shown ribavirin to have in vitro activities against SARS-coronavirus, alone or in combination with other agents. Ribavirin should be tested in future randomized controlled studies in combination with other potential antiviral agents for SARS.

References

  1. Chiou, HE, Liu, CL, Buttrey, MJ, et al (2005) Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers. Chest 128,263-272[Abstract/Free Full Text]
  2. Chu, CM, Poon, LL, Cheng, VC, et al Initial viral load and the outcomes of severe acute respiratory syndrome (SARS). Can Med Assoc J 2004;171,1349-1352[Abstract/Free Full Text]
  3. Chu, CM, Cheng, VC, Hung, IF, et al Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59,252-256[Abstract/Free Full Text]
  4. Chen, F, Chan, KH, Jiang, Y, et al In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol 2004;31,69-75[ISI][Medline]
  5. Morgenstern, B, Michaelis, M, Baer, PC, et al Ribavirin and interferon-ß synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem Biophys Res Commun 2005;326,905-908[CrossRef][ISI][Medline]



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Ribavirin should not be used for treatmentof SARS-CoV
Dale Barnard
Chest Online, 16 Dec 2005 [Full text]
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