The aim of this randomized controlled trial is to restore immune function by selectively removing three mediators largely contributing to sepsis-induced immunosuppression from extracorporeal circulation.

The treatment safety and the kinetics of specific biomarkers will be assessed to evaluate the selection of the treatment regimen. In a first step, 16 patients will be randomized 1:1 into two arms:

Treatment arm 1: One treatment of 2 hours per day for a maximum of five days or until ICU discharge or death or withdrawal of consent, whichever occurs first.

Control arm: Five consecutive days following the first mHLA-DR measurement post study randomization, or until ICU discharge or death or withdrawal of consent, whichever occurs first

And the end of this treatment phase, it will be decided whether the dosage regimen of HemoSystem REBOOT needs to be adapted and another eight patients have to be enrolled with 2 treatments per day, and a maximum of five treatments.

Inclusion Criteria:

1. Age ≥ 18 years

2. Written informed consent according to national requirements.

3. Hospitalized in ICU or IMC at randomization.

4. Expected length of intensive care unit stay (from randomization) >48 hours.

5. Suspected or confirmed bacterial sepsis.

6. Septic shock diagnosis at any time during ICU/IMC stay according to Sepsis - 3 criteria definition:

   1. an infection (suspected or confirmed);
   2. persisting hypotension requiring any dose of vasopressors (norepinephrine, vasopressin) to maintain a systemic mean blood pressure > 65 mmHg despite adequate fluid resuscitation (minimum of 30 ml/kg crystalloids);
   3. elevated lactate ≥ 2.0 mmol/L with suspected hypoperfusion.

7. Persistent immunosuppression defined as mHLA-DR expression levels < 5600 Ab/cell (Cyto-Chex tubes) in at least two consecutive measurements 20-72 hours apart.

Exclusion criteria:

1. Current ongoing chronic treatment using immunosuppressive biologicals or active lymphocyte therapy (e.g. endoxan, rituximab) or corticosteroid use at a dose > 10 mg/day equivalent of prednisone. However, acute treatment using a maximum dose of hydrocortisone of 200 mg/day for sepsis is allowed.

2. Patient with preexisting known severe immune deficiency (e.g. severe combined immunodeficiency, HIV infection, AIDS).

3. Active or planned extracorporeal membrane oxygenation treatment.

4. Active or planned other extracorporeal blood purification treatments with systems like CytoSorb®, ToraymyxinTM, Gambro Adsorba, etc.

5. Patients post solid-organ transplantation.

6. Known active malignancy (i.e. patients under active anti-malignant treatment).

7. Acute severe burn injury > 20% of the body surface area.

8. Contraindication to use the HemoSystem:

   1. Sensitivity / allergy to HemoSystem components
   2. Body weight < 50 kg
   3. Platelets count < 20,000/µL
   4. History of heparin-induced thrombocytopenia.

9. Females who are known to be pregnant or known to be breastfeeding (b-HCG testing performed in female patients aged < 55 years),

10. Moribund patient with life expectancy < 48h

11. Known history of bleeding disorders or severe coagulopathies (e.g., Hemophilia A, Hemophilia B, Idiopathic Thrombocytopenic Purpura, Von Willebrand Disease types I, II, and III)