A Trial of Validation and Restoration of Immune Dysfunction in Severe Infections and Sepsis

Inclusion Criteria: * Age equal to or above 18 years * Male or female gender * In case of women, unwillingness to remain pregnant during the study period * Written informed consent provided by the patient or by one first-degree relative/spouse in case of patients unable to consent * Community-acquired pneumonia or hospital-acquired pneumonia or ventilator-associated pneumonia or primary bacteremia or acute cholangitis * Sepsis defined by the Sepsis-3 definitions. * Patients with laboratory diagnosis of MALS or hypo-inflammation (immune-paralysis) based on two consecutive blood sampling with 24 hours apart. MALS is defined as the presence of ferritin \>4,420 ng/ml and hypo-inflammation as HLA-DR expression on CD14-monocytes (co-expression) less than 30% Exclusion Criteria: * Age below 18 years * Denial for written informed consent * Acute pyelonephritis or intraabdominal infection other than AC, meningitis or skin infection. It is explicitly stated that in the case of a patient with both AC and any other type of intraabdominal infection, the patient cannot be enrolled. * Any stage IV malignancy * Any do not resuscitate decision * In the case of BSI, patients with blood cultures growing coagulase-negative staphylococci or skin commensals or catheter-related infections cannot be enrolled. * Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB * Infection by the human immunodeficiency virus (HIV) * Any primary immunodeficiency * Oral or…