Ribavirin plus Interferon or Oseltamivir in Severe Middle East Respiratory Syndrome Infection

Abstract

Background: Middle East respiratory syndrome (MERS) is associated with significant mortality with no approved antiviral therapy. Objectives: The aim of this study was to compare the efficacy and safety of the combination of ribavirin and PEG-interferon α-2a (RIF), oseltamivir, and supportive care (SC) alone in MERS patients. Materials and Methods: Retrospective cohort for all patients admitted to the intensive care unit with severe symptomatic laboratory-confirmed MERS infection between September 2013 and February 2017. Patients were divided into two pairwise comparisons: RIF and oseltamivir combined (antivirals) vs. SC; and RIF vs. oseltamivir. The primary endpoint was 60-day mortality. Secondary endpoints were the requirement for mechanical ventilation (MV) and renal replacement therapy (RRT), and laboratory changes. Results: A total of 113 patients met the study inclusion criteria; 77 received antivirals (47 received RIF and 30 oseltamivir), and 36 SC. The 60-day mortality rate was 36% with antivirals vs. 50% with SC (P = 0.136), and 45% with RIF vs. 23% with oseltamivir (P = 0.092). The MV requirement was 42% with antivirals vs. 65% with SC (P = 0.083), and 54% with RIF vs. 27% with oseltamivir (P = 0.067). The RRT requirement was 29% with antivirals vs. 31% with SC (P = 0.943), and 40% with RIF vs. 14% with oseltamivir (P = 0.019). The median hemoglobin decrease with RIF was 4 g/dL vs. 1 with oseltamivir (P < 0.001); the WBC decrease with RIF was 1.3 vs. 0.2 with oseltamivir (P = 0.007); the blood glucose increase with RIF was 143 mg/dL vs. 89 with oseltamivir (P = 0.036), and the indirect bilirubin increase with RIF was 0.4 mg/dL vs. 0.3 with oseltamivir (P = 0.023). Conclusions: In this study, the use of RIF or oseltamivir in severe MERS infections did not significantly reduce 60-day mortality, nor the requirement for MV or RRT. Furthermore, the subgroup that received oseltamivir had more favorable renal, hepatic, and hematological outcomes than RIF. Larger, prospective, well-designed studies are warranted to confirm these findings.