SummaryBackgroundInfluenza causes significant morbidity and mortality despite currently available treatments. Anecdotal reports suggest plasma with high antibody titers towards influenza may be of benefit in the treatment of severe influenza.MethodsWe conducted a randomized, open-label, multicenter phase 2 trial at 29 academic medical centers in the United States to assess the safety and efficacy of anti-influenza plasma with hemagglutination inhibition (HAI) antibody titers of ≥ 1:80 to the infecting strain. Hospitalized children and adults (including pregnant women) with severe influenza A or B (defined as hypoxia or tachypnea) were randomly assigned to receive either 2 units (or pediatric equivalent) of anti-influenza plasma plus standard care (P+S), versus standard care alone (S), and were followed for 28 days. The primary endpoint was time to normalization of patients’ respiratory status (respiratory rate of ≤ 20 for adults or age defined thresholds of 20–38 for children), and a room air saturation of oxygen ≥ 93%. ClinicalTrials.gov Identifier: NCT01052480FindingsBetween January 13, 2011 and March 2, 2015, 113 participants were screened, and 98 were randomized. Of the participants with confirmed influenza, 28 of 42 (67%) of P+S participants normalized their respiratory status by Day 28, as compared to 24 of 45 (53%) of S participants (p=0·069). The estimated hazard ratio comparing P+S to S was 1·71 (95% CI: 0·96 to 3·06). Six participants died, 1 (2%) and 5 (10%) from the P+S and S arms respectively (p=0·093). P+S participants had non-significant reductions in days in hospital (median 6 vs. 11 days, p=0·13) and days on mechanical ventilation (median 0 vs. 3 days, p=0·14), and significantly improved clinical status at Day 7 (p=0·020). Fewer P+S participants experienced SAEs compared to S recipients (20% vs. 38%, p= 0·041), the most frequent of which were acute respiratory distress syndrome (1 [2%] vs 2 [4%]) and stroke (1 [2%] vs 2 [4%]).InterpretationResults from this Phase II randomized trial of immune plasma for the treatment of severe influenza provides support for a possible benefit of immunotherapy across the primary and secondary endpoints. A Phase III randomized trial is now underway to further evaluate this intervention.

Background Plasma transfusion is a critical treatment in managing bleeding patients. In an effort to make plasma immediately available in spite of the limited amount of AB plasma, providers have begun using A plasma in life‐threatening emergencies. As this practice becomes widely adopted it is important to evaluate safety. Hemolytic transfusions reactions are underreported, and hemolysis may be subclinical. Study Design and Methods A retrospective study was performed at the University of Florida/Shands Hospital of B and AB patients who received 1 unit or more of A plasma. Patient charts were reviewed and data collected included age; sex; mortality; intensive care unit (ICU) length of stay; and laboratory tests used in identifying hemolysis including direct antiglobulin test, lactate dehydrogenase, haptoglobin, indirect bilirubin, aspartate aminotransferase, urinalysis, hemoglobin, and hematocrit. The primary end points of the study were immune mediated hemolysis, mortality, and length of ICU stay. Results Ninety‐three patients were identified as eligible for the study. One patient suffered a delayed hemolytic transfusion reaction determined to be due to an anti‐Jka. No evidence of hemolysis due to ABO‐incompatible plasma transfusion was identified. The volume of A plasma transfused was found to be weakly related to mortality and ICU stay. Conclusion No evidence of ABO immune‐mediated hemolysis was observed in the patient population. The results of the study support the safety of A plasma transfusion in B and AB patients. We hypothesize the relationship observed between A plasma volume and mortality/ICU stay may be from collinearity with disease severity.