title: Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study.
abstract: BACKGROUND
  Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only.
  
  
  METHODS
  In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used χ(2) and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables.
  
  
  RESULTS
  We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5·88 × 10(9)/L [SD 3·95] vs 9·88 × 10(9)/L [6·63]; p=0·023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0·004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0·54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4·32 g/L [SD 2·47] vs 2·14 g/L [1·90]; p=0·002).
  
  
  CONCLUSIONS
  In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.
  
  
  BACKGROUND
  None.
authors.affiliation: Division of Infectious Diseases, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Omrani
authors.affiliation: Division of Infectious Diseases, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Mustafa M
authors.initials: MM
authors.lastname: Saad
authors.affiliation: Department of Infection Prevention and Control, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Kamran
authors.initials: K
authors.lastname: Baig
authors.affiliation: Division of Infectious Diseases, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Abdelkarim
authors.initials: A
authors.lastname: Bahloul
authors.affiliation: Department of Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abdul-Matin
authors.affiliation: Division of Infectious Diseases, Prince Sultan Military Medical City, Riyadh, Saudi Arabia; Department of Infection Prevention and Control, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Amal Y
authors.initials: AY
authors.lastname: Alaidaroos
authors.affiliation: Department of Critical Care, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Ghaleb A
authors.initials: GA
authors.lastname: Almakhlafi
authors.affiliation: Department of Critical Care, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Albarrak
authors.affiliation: Al-Faisal University and Ministry of Health, Riyadh, Saudi Arabia. Electronic address: zmemish@yahoo.com.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Memish
authors.affiliation: Division of Infectious Diseases, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Albarrak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D018352:Coronavirus Infections / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D065207:Middle East Respiratory Syndrome Coronavirus / Q000187:drug effects*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D012529:Saudi Arabia; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin