Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Open-Label, Phase 2, Multicenter Safety and Exploratory Efficacy Study of Investigational Anti-Influenza Immune Plasma for the Treatment of Influenza (IRC002)
Brief Summary: This randomized, open-label, multicenter phase 2 trial will assess the safety, efficacy, and pharmacokinetics (PK) of anti-influenza plasma in subjects with influenza A or B. Hospitalized subjects with influenza A or B that have either a low oxygen level or a high respiratory rate will be eligible for study participation. This study will enroll adults, children and pregnant women.


Options:
A: Inclusion Criteria:

* Patients with PCR confirmed COVID disease
* Admitted to the hospital
* The most recent PCR positive sample is \<96hrs old
* Written informed consent by patient or legal patient representative
* Age at least 18 years

Exclusion Criteria:

* Participation in another intervention trial on the treatment of COVID-19 that falls under the Dutch law human research (WMO) and in which individual patients are randomized to different treatment options
* Known IgA deficiency
* Invasive ventilation for already \>96 hours

Donors: Eligibility for plasma donation

Inclusions Criteria:

* A history of COVID infection that was documented by PCR
* Known ABO-Resus(D) blood group
* A screening for irregular antibodies with a titer ≤ 1:32
* Asymptomatic for at least 14 days
* Written informed consent regarding the plasmapheresis procedure
* Tested negative for HIV, HBV, HCV, HEV, HTLV and syfilis

Exclusion Criteria:

* Age \<18 years and \> 65 years
* Weight \<50kg
* Medical history of heart failure
* History of transfusion with red blood cells, platelets or plasma
* History of organ- or tissue transplant
* A cumulative stay in the United Kingdom of ≥ 6 months in the period between 01-01-1980 and 31-12-1996
* A history of i.v. drug use
* Insulin dependent diabetes
* An underlying severe chronic illness (i.e. history of heart failure, cancer or stroke)
* Tested positive for HLA- or HNA-antibodies
B: Inclusion Criteria:

* age at least 18 years
* hospitalization in an intensive care unit participating to the study
* medical diagnosis with SARS-CoV-2 pneumonia as defined by both:

  * extended interstitial pneumonia on CT scan or a chest X-ray, consistent with viral pneumonia, within 10 days prior to inclusion
  * Positive result of SARS-CoV-2 PCR test, or any emerging and validated diagnostic laboratory test for COVID-19, within 15 days prior to inclusion
* under mechanical ventilation administered through an endotracheal tube, for less than 5 days
* prior Clinical Frailty Scale \< 6.
* written consent of the patient, or - if impossible - of a relative acting as the legal representative, or - if impossible - of a physician from a non-participating department of the same hospital acting as an impartial witness .

Exclusion Criteria:

* Pregnancy
* Prior episode of transfusion-related side effect
* Medical decision to limit therapy
* Current participation in another trial testing a COVID-19 therapy
C: Inclusion Criteria:

1. Written informed consent prior to performing study procedures. Witnessed oral consent will be accepted in order to avoid paper handling. Written consent by patient or representatives will be obtained as soon as possible.
2. Male or female adult patient ≥18 years of age at time of enrolment.
3. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR in naso/oropharyngeal swabs or any other relevant specimen in the ongoing COVID-19 symptomatic period. Alternative test (i.e antigenic tests) are also acceptable as laboratory confirmation if their adequate specificity has been accepted by the sponsor.
4. Patients requiring hospitalization for COVID-19 without mechanical ventilation (invasive or non-invasive) or high flow oxygen devices and at least one of the following:

   * Radiographic evidence of pulmonary infiltrates by imaging (chest x-ray, CT scan, etc.), OR
   * Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air that requires supplemental oxygen.
5. No more than 7 days between the onset of symptoms (fever or cough) and treatment administration day.

Exclusion Criteria:

1. Requiring mechanical ventilation (invasive or non-invasive) or high flow oxygen devices.
2. More than 7 days since symptoms (fever or cough).
3. Participation in any other clinical trial of an experimental treatment for COVID-19.
4. In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
5. Any incompatibility or allergy to the administration of human plasma.
6. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR \<30).
D: Inclusion Criteria:

* Diagnosis of influenza A or B within 72 hours prior to enrollment (by local assay including rapid antigen, direct fluorescent antibody (DFA), polymerase chain reaction (PCR), or culture, and must be able to detect and distinguish influenza A from influenza B)
* Hospitalization for signs and symptoms of influenza (decision for hospitalization will be up to the individual treating clinician).
* Abnormal respiratory status, defined as room air saturation of oxygen (SaO2) less than 93% or tachypnea (respiratory rate above an age adjusted normal range)
* Agree to the storage of specimens and data
* ABO compatible plasma available on site or available within 24 hours after randomization with activity against locally circulating strains of influenza

Exclusion Criteria:

* Receipt of non-licensed treatment for influenza within the last 2 weeks (or plans to receive any time during the study). This does not include licensed drugs at non approved doses, off-label indications, or drugs available under an Emergency Use Authorization (EUA).
* History of severe allergic reaction to blood products (as judged by the investigator).
* Medical conditions for which receipt of 500 mL volume (or 8 mL/kg for pediatric patients) may be dangerous to the subject (e.g. decompensated congestive heart failure \[CHF\], etc.)
* Clinical suspicion that etiology of acute illness is primarily due to a condition other than active influenza virus replication (e.g., a bacterial or fungal infection)

Answer: D