Table 1 Inclusion and exclusion criteria

❖ Male or female ≥18 years and ≤ 85 years

❖ Evidence of multiorgan failure (severe COVID-19)

❖ Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception during the clinical trial (oral contraception, implant or IUD

❖ Mechanically ventilated (including ECMO)

❖ Willing and able to provide written informed consent prior to performing study procedures

❖ Receipt of immunoglobulins or any blood products in the past 30 days

❖ Hospitalized for COVID-19

❖ Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the investigator, would affect subject safety and/or compliance

❖ Positive SARS-CoV-2 RT-PCR in any body specimen (nasopharynx, saliva, sputum) ≤ 10 days before enrolment

❖ End-stage renal disease (eGFR < 15 ml/min/1,73 m²)

❖ Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chest-imaging [Chest X-ray or computed tomography])

❖ Child-Pugh C stage liver cirrhosis

❖ Requiring O2 supplement ≤6 L/min at screening

❖ Decompensated cardiac insufficiency

❖ Requiring O2 supplementation with SpO2 ≥ 94% on O2 therapy at screening

❖ History of active drug abuse

❖ First onset of COVID-19 symptoms ≤10 days, among fever and/or chills, headache, myalgias, cough, shortness of breath, whichever as occurred fist

❖ Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components

❖ WOCBP must have a negative urinary pregnancy test the day of inclusion

❖ WOCBP without contraceptive method, or with positive pregnancy test, breastfeeding, or planning to become pregnant during the study period

❖ All sexually active male subjects must agree to use an adequate method of contraception throughout the study period and for 90 days after the last dose of study drug and agree to no sperm donation until the end of the study, or for 90 days after the last dose of XAV-19, whichever is longer

❖ Current documented and uncontrolled bacterial infection

❖ Patients with French social security

❖ Prior severe (grade 3) allergic reactions to plasma transfusion

❖ Patient participating in another interventional clinical trial

❖ Life expectancy estimated to be less than 6 months

❖ Patient under guardianship or trusteeship