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.

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

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.

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.

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.

Forest plot of pooled odds ratios (ORs) of mortality following treatment with convalescent plasma or convalescent serum, excluding studies with <5 patients (n = 5 studies). Weights are from random-effects analysis. Abbreviation: CI, confidence interval.