title: The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis.
abstract: BACKGROUND
  Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence.
  
  
  METHODS
  Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken.
  
  
  RESULTS
  We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14-.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified.
  
  
  CONCLUSIONS
  Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection.
authors.affiliation: East Midlands Centre, Public Health England.
authors.forename: John
authors.initials: J
authors.lastname: Mair-Jenkins
authors.affiliation: Field Epidemiology Training Programme, Public Health England, London Field Epidemiology Service, Public Health England, Liverpool.
authors.forename: Maria
authors.initials: M
authors.lastname: Saavedra-Campos
authors.affiliation: Roslin Institute, University of Edinburgh, Midlothian.
authors.forename: J Kenneth
authors.initials: JK
authors.lastname: Baillie
authors.affiliation: Field Epidemiology Service, Public Health England, Liverpool.
authors.forename: Paul
authors.initials: P
authors.lastname: Cleary
authors.affiliation: East Midlands Centre, Public Health England.
authors.forename: Fu-Meng
authors.initials: FM
authors.lastname: Khaw
authors.affiliation: Respiratory Medicine, Nottingham University Hospitals NHS Trust.
authors.forename: Wei Shen
authors.initials: WS
authors.lastname: Lim
authors.affiliation: East Midlands Centre, Public Health England.
authors.forename: Sophia
authors.initials: S
authors.lastname: Makki
authors.affiliation: Institute of Care and Practice Improvement, University of the West of Scotland, Hamilton, United Kingdom.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Rooney
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Nguyen-Van-Tam
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, Nottingham.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Beck
mesh_terms: D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000188:drug therapy / Q000276:immunology; D010949:Plasma / Q000276:immunology*; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000276:immunology; D012306:Risk; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D007136:Immunoglobulins
keywords: MERS coronavirus; convalescent plasma; meta-analysis; severe acute respiratory infection; systematic review