Inclusion Criteria

Inclusion Criteria for Enrollment (Screening):

• Subjects must be aged 2 weeks or older.
• Hospitalization due to signs and symptoms of influenza (decision for hospitalization will be up to the individual treating clinician).
• Study plasma available on-site or available within 24 hours after randomization.
• Not previously screened nor randomized in this study.

Inclusion Criteria for Randomization:

• Locally determined positive test for influenza A (by polymerase chain reaction [PCR], other nucleic acid testing, or by rapid Ag) from a specimen obtained less than or equal to 48 hours prior to randomization.
• Onset of illness less than or equal to 6 days before randomization, defined as when the subject first experienced at least one respiratory symptom or fever.
• Hospitalized due to influenza, with anticipated hospitalization for more than 24 hours after randomization. Criteria for hospitalization will be up to the individual treating clinician.
• Willingness to have blood and respiratory samples obtained and stored.
• Willingness to return for all required study visits and participate in study follow up.
• National Early Warning (NEW) score greater than or equal to 3 within 12 hours prior to randomization (or PEW [pediatric early warning] score greater than or equal to 3 within 12 hours prior to randomization).
• ABO-compatible plasma available on-site or available within 24 hours after randomization.

Exclusion Criteria

• Strong clinical evidence in the judgment of the site investigator that the etiology of illness is primarily bacterial super-infection in origin. Co-infection would be allowed, as there may be benefit to resolving influenza illness faster. Super-infection, where influenza illness occurred and is resolving, and new bacterial illness causing deterioration should be excluded.
• Prior treatment with any anti-influenza investigational drug, or use of intravenous immune globulin (IVIG) or plasma therapy for influenza within 30 days prior to screening. Other investigational drug therapies (non-influenza) are allowed.
• History of allergic reaction to blood or plasma products (as judged by the site investigator).
• A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy). Prior IVIG use alone would not meet exclusion criteria, but the investigator should consider the potential for a hyper-coagulable state.
• Subjects who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol, including being uncontactable following discharge from hospital.
• Medical conditions for which receipt of 450-700 mL of intravenous fluid may be dangerous to the subject (e.g., decompensated congestive heart failure).