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

John Mair-Jenkins, Maria Saavedra-Campos, J Kenneth Baillie, Paul Cleary, Fu-Meng Khaw, Wei Shen Lim, Sophia Makki, Kevin D Rooney, Jonathan S Nguyen-Van-Tam, Charles R Beck, Convalescent Plasma Study Group, John Mair-Jenkins, Maria Saavedra-Campos, J Kenneth Baillie, Paul Cleary, Fu-Meng Khaw, Wei Shen Lim, Sophia Makki, Kevin D Rooney, Jonathan S Nguyen-Van-Tam, Charles R Beck, Convalescent Plasma Study Group

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.

Keywords: MERS coronavirus; convalescent plasma; meta-analysis; severe acute respiratory infection; systematic review.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram. aRecords were rejected for the following reasons: not population of interest, 12 records (1 in French, 1 in German, 1 in Italian, and 1 in Korean); no intervention of interest, 15 (1 in German); not suitable comparator, 1; nonhuman study, 1; and no outcome of interest, 7.
Figure 2.
Figure 2.
Summary of outcome level risk of bias assessments in eligible observational studies, using the Newcastle Ottawa tool (excluding prospective cohort studies; 44 outcomes from 25 studies).
Figure 3.
Figure 3.
Forest plot of pooled odds ratios (ORs) of mortality following treatment with convalescent plasma or convalescent serum (n = 8 studies). Weights are from random-effects analysis. Abbreviation: CI, confidence interval.
Figure 4.
Figure 4.
Forest plot of pooled odds ratios (ORs) of mortality following treatment with convalescent plasma or convalescent serum, excluding studies with

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