Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Double-Blind, Phase 3 Study Comparing the Efficacy and Safety of High-Titer Versus Low-Titer Anti-Influenza Immune Plasma for the Treatment of Severe Influenza A
Brief Summary: This study assessed the efficacy and safety of anti-influenza immune plasma, as an addition to standard of care antivirals, in participants hospitalized with severe influenza A infection.


Options:
A: Inclusion Criteria:

* All genders
* Age \> 18 yrs and \< 90 yrs
* Must have laboratory confirmed COVID-19
* Must provide informed consent
* Must have severe or immediately life-threatening COVID-19,

Severe disease is defined as:

* dyspnea,
* respiratory frequency ≥ 30/min,
* blood oxygen saturation ≤ 93%,
* partial pressure of arterial oxygen to fraction of inspired oxygen ratio \< 300
* lung infiltrates \> 50% within 24 to 48 hours

Life-threatening disease is defined as:

* respiratory failure,
* septic shock
* multiple organ dysfunction or failure

Exclusion Criteria:

* No gender exclusion
* Age \< 18 yrs and \> 90 yrs
* COVID-19 negative
B: Inclusion Criteria for Enrollment (Screening):

* Subjects must be aged 2 weeks or older.
* Hospitalization due to signs and symptoms of influenza.

  \* Note: The decision for hospitalization will be made by the treating clinician. To be considered eligible, the hospitalization may either be an initial hospitalization, or a prolongation of a hospitalization due to a respiratory illness that was found to be from influenza. Influenza could be a component of a larger respiratory syndrome (i.e. COPD exacerbation thought to be triggered by influenza). However, respiratory syndromes that are not likely due to the virus should not be included (i.e. a subject that had mild influenza then developed pulmonary embolism and respiratory distress from the embolism).
* Study plasma available on-site or available within 24 hours after randomization.
* Not previously screened nor randomized in this study.
* Willingness to have blood and respiratory samples obtained and stored.
* Willingness to return for all required study visits and participate in study follow up.

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.
* Note: For subjects with chronic respiratory symptoms (chronic cough, or COPD with baseline dyspnea), the onset of symptoms is defined as the point when the symptoms changed during this illness). 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.
* National Early Warning (NEW) or Pediatric Early Warning (PEW) 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 for Randomization:

* 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 (e.g., if the subject's respiratory infection is thought unlikely to benefit from additional antiviral therapy, this exclusion criteria would be met).
* Prior treatment with any anti-influenza investigational drug, anti-influenza investigational intravenous immune globulin (IVIG), or anti-influenza investigational plasma therapy within 30 days prior to screening. Other investigational drug therapies (non-influenza) and administration of plasma and/or IVIG for non-influenza reasons 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 not contactable following discharge from hospital.
* Medical conditions for which receipt of 500-600 mL (or pediatric equivalent) of intravenous fluid may be dangerous to the subject (e.g., decompensated congestive heart failure).
C: Inclusion Criteria:

* age \>=18 yrs
* positive for reverse transcription polymerase chain reaction (RT-PCR) severe acute respiratory syndrome (SARS)-CoV-2
* Acute respiratory distress syndrome (ARDS) moderate to severe, according to Berlin definition, lasting less than10 days
* Polymerase chain reaction (PCR) increased by 3.5 with respect to baseline or \>1.8 mg/dl
* need for mechanical ventilation or continuous positive airway pressure (CPAP)
* signed informed consent unless unfeasible for the critical condition

Exclusion Criteria:

* Moderate to severe ARDS lasting more than 10 days
* proven hypersensitivity or allergic reaction to hemoderivatives or immunoglobulins
* consent denied
D: Inclusion Criteria:

* Above 18 years of age
* Have positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs
* Admitted in isolation ward and ICU of institutes affiliated with DUHS
* have severe or critical COVID 19 as judged by the treating physician
* Consent given by the patient or first degree relative

Exclusion Criteria:

* Pregnancy
* Previous allergic reaction to immunoglobulin treatment
* Ig A deficiency
* Patient requiring 2 inotropic agents to maintain blood pressures
* Known case of any autoimmune disorder
* Acute kidney injury or chronic renal failure
* Known case of thromboembolic disorder
* Aseptic meningitis

Answer: B