A Randomized Study of Immune Plasma for the Treatment of Severe Influenza

Beigel, John H.; Tebas, Pablo; Elie-Turenne, Marie-Carmelle; Bajwa, Ednan; Bell, Todd E.; Cairns, Charles B.; Shoham, Shmuel; Deville, Jaime G.; Feucht, Eric; Feinberg, Judith; Luke, Thomas; Raviprakash, Kanakatte; Danko, Janine; O’Neil, Dorothy; Metcalf, Julia A.; King, Karen; Burgess, Timothy H.; Aga, Evgenia; Lane, H. Clifford; Hughes, Michael D.; Davey, Richard T.

Participants randomized to receive plasma had about 1 log copies/mL lower nasal and oral influenza viral loads (detected by quantitative PCR) at baseline (nasal: median 2·8 vs. 3·8 log 10 copies/mL; oral 2·4 vs. 3·3 log 10 copies/mL), although viral loads in the 23 participants who had an endotracheal aspirate (5·0 vs. 5·1 log 10 copies/mL) were similar. (Table 3 ) There was no appreciable difference in time to virus becoming undetectable (nasal: p = 0·95; oral: p=0·56) ( Figure 3) The HAI titer achieved by infused plasma cannot be determined separately from the participant's pre-existing immunity and immune response. For H1N1 2009, which was a strain in circulation throughout the study, the geometric mean HAI titer in study participants at baseline was 1:26·4 [95% CI: Thirty percent of the study population had serious adverse events (SAEs). Fewer plasma recipients than controls had SAEs (9 (20%) vs. 20 (39%), p= 0·041). The most common SAEs were acute respiratory distress syndrome and stroke. Each of these occurred in 3 participants (3%): 1 plasma recipient, 2 controls (Table 4 ). No category of SAE appeared more frequently among plasma recipients. The most common adverse events occurring in the first 7 days were hyperglycemia, increased aspartate aminotransferase, diarrhea, anemia, and fever (Table 5 ).