We agree with Drs. Logtenberg and Bilo that the possible benefit of convalescent blood products, including plasma, for treating Spanish influenza pneumonia may not have been entirely due to the presence of neutralizing antibodies.

Plasma is a complex mixture of immunoglobulins, coagulation factors, cytokines, and other immunologically and physiologically active molecules. It is sometimes used to treat patients with circulatory collapse—presumably because it expands volume while increasing oncotic pressure, as theorized by Drs. Logtenberg and Bilo. Furthermore, both adaptive and innate immune responses likely contribute to the control of influenza infections. Products of the innate immune system in plasma may have contributed to controlling the infection in the patient in Drs. Logtenberg and Bilo's study and in the patients reported in our paper.

However, the therapeutic effect of passively delivered neutralizing antibodies cannot be dismissed. Multiple strains of H3N2 influenza have circulated globally since the illness first arose in 1968, and many if not most plasma donors have been exposed to multiple wild-type H3N2 strains, seasonal influenza vaccines, or both. The fresh frozen plasma units transfused into the patient in their report may have contained neutralizing H3 antibodies. We believe that Drs. Logtenberg and Bilo's experience suggests that patients with serious seasonal H1 or H3 influenza infections may benefit from receiving transfusions with plasma with an unknown titer of neutralizing antibodies or preferably with plasma or purified immunoglobulin that is specifically selected for a high titer of H1 and H3 antibodies.