Preemptive Use of Convalescent Plasma for High-risk Patients With COVID-19

This is an open-label non-controlled, non-randomised interventional study. Study population consist in immunocompromised patients and older adults with or without co-morbidities.

Included patients will receive at least one unit of convalescent plasma with NTAB titer ≥1:160 or equivalent at maximum 3-7 days after diagnosis by RT-PCR or symptom onset or if having mild-moderate disease (WHO scale <4).

Patients will be followed-up up to 28 days to assess progression to WHO scale 4 disease, and 28-days mortality and viral load kinetics.

• SARS-CoV-2 convalescent plasma (Drug): Included patients will receive at least one unit of convalescent plasma with NTAB titer ≥1:160 at maximum 3-7 days after diagnosis by RT-PCR or symptom onset. A second unit of plasma from a different donor can be proposed 24h after the first unit if immunocompromised and/or the patient received less than 3-5ml/kg of plasma volume. Additional units can be exceptionnally infused, at the investigator discretion.

Primary outcomes

• Proportion of patient that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement) [7 days after plasma infusion]
• Proportion of patient that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement) [14 days after plasma infusion]
• Proportion of death [28 days after plasma infusion]

Secondary outcomes

• Proportion of patients with cleared nasopharyngeal viral load [7 days after plasma infusion]: Cleared viral load is defined as CT value ≥30
• Proportion of patients with cleared nasopharyngeal viral load [14 days after plasma infusion]: Cleared viral load is defined as CT value ≥30

Other outcomes

• Proportion of patients that progress to WHO 8 ordinal scale ≥ 4 (oxygen requirement) [21 days after plasma infusion]
• Proportion of patients with cleared nasopharyngeal viral load [21 days after plasma infusion]: Will be evaluated if CT< 30 at 14 days

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Immunocompromised patients defined as

   1. Solid organ transplant ≤1 year before inclusion or treated for acute or chronic rejection episode or
   2. Allogeneic stem cell transplant recipients ≤2 years before inclusion or treated for acute GvHD ≥grade 2 or chronic moderate-severe GvHD or
   3. Active solid or haematological oncological disease with curative perspectives or
   4. HIV infection with CD4<350 or
   5. Hypogammaglobulinemia and other severe genetic immunological defect or
   6. Auto-immune disease with biological immunosuppressive treatment* or
   7. Other significant immunosuppressive condition such as IgG <6, treamtent with Rituximab or other biological lymphopenic treatment AND

      * Age ≥ 18 years old and
      * 2 distinct ABO group determination and
      * Positive RT-PCR for SARS-CoV-2 on a respiratory tract sample of ≤ 7 days and days post symptom onset (DPOS) ≤ 7 days at inclusion and/or
      * No oxygen requirement (WHO 8 ordinal scale < 4): asymptomatic, mild or moderate disease, or O2 saturation ≥ 90% at room temperature and
      * Compatible ABO donor with neutralizing antibodies (NTAB) ≥1 :160 or equivalent according to predefined antibody commercial assays cut-offs (see Study procedures)
      * RT-PCR on a respiratory tract sample with CT value<20 or ascending kinetics at the time of infusion (highly suggested but not necessary)
2. Older adults defined as Age ≥ 75 years old or ≥ 65 years old with at least one co-existing condition

   * Arterial hypertension under pharmacological treatment
   * Diabetes in treatment
   * Obesity (BMI ≥ 30 kg/m2)
   * Chronic obstructive pulmonary disease stade GOLD ≥2
   * Respiratory insufficiency due to any pneumopathy or neurologic disease.
   * Cardiovascular disease as defined by either known coronary heart disease, history of ischemic or hemorrhagic stroke or cardiac insufficiency (ejection fraction <40%)
   * Chronic kidney disease (GFR<60 ml/min) AND
   * 2 distinct ABO group determination and
   * Positive RT-PCR for SARS-CoV-2 on a respiratory tract sample of ≤ 3 days and days post symptom onset (DPOS) ≤ 3 days at inclusion or RT-PCR on a respiratory tract sample with CT value<20 or ascending kinetics at the time of perfusion and
   * No additional oxygen requirement compared to baseline (WHO 8 ordinal scale < 4): asymptomatic, mild or moderate disease and
   * Compatible ABO donor with neutralizing antibodies (NTAB) ≥1 :160 or equivalent according to predefined antibody commercial assays cut-offs (see Study procedures)

Exclusion criteria:

Seroconversion at the time of inclusion

* Palliative care
* No signed informed consent
* History of previous transfusion-related Grade 3 adverse event according to Swissmedic definitions
* Disseminated intravascular coagulopathy (depending on specialist evaluation)
* Uncontrolled acute hypervolemia

• Laurent Kaiser, MD, Principal investigator, University Hospital, Geneva
• Enos Bernasconi, MD, Principal investigator, Ospedale Regionale di Lugano
• Véronique Erard, MD, Principal investigator, HFR-Fribourg Hôpital Cantonal
• Maja Weisser, MD, Principal investigator, Klinik Infektiologie & Spitalhygiene