Critical illnesses represent a significant physiological assault that triggers changes in the patient's immune system, resulting in an immunopotentiating response (systemic inflammatory response syndrome, SIRS) and an immunosuppressive response (compensatory anti-inflammatory response syndrome, CARS). The balance between SIRS and CARS is essential for the patient to return to a state of immune homeostasis and accelerate the healing process. However, when CARS is disproportionately intense, it leads to a state of immunoparalysis, which predisposes the patient to vulnerability to opportunistic infections, associated with a peak in late mortality. The majority of patients admitted to the ICU are considered immunocompetent. However, the investigators suspect that a significant proportion of them exhibit predominance of CARS and a state of functional immunosuppression. There is currently no diagnostic test to determine whether a patient is functionally immunocompetent at a specific point in time.

The goal of this observational study is to learn about the immune system dysfunction occurring in critical illness. The main questions it aims to answer are:

• What is the prevalence of immune system dysfunction in critical illness?
• Does immune system dysfunction affect multiple organ failure trajectory and mortality in critical illness?
• Is immune system dysfunction related to an increased risk of opportunistic hospital-acquired infections in critical illness?
• Is immune system dysfunction related to age, fragility, nutritional status or previous comorbidities in critical illness?

To answer these questions, the investigators will prospectively study a population of critically ill patients, defined by the presence of organ failure. The investigators will analyse a panel of genes and molecules involved in immunological synapse, using peripheral blood samples at different moments of the evolution of critical illness. Based on the analysis, the investigators will classify the patients' functional immune status and correlate it with the outcomes.

Inclusion Criteria:

• Failure of one or more organs, assessed by a Sequential Organ Failure Assessment Score (SOFA) ≥4 within the first 24 hours of admission to the Intensive Care Unit (ICU). At least one of the physiological systems involved must be in the category of organ failure and, therefore, score ≥3.
• Informed consent to participate in the study.
• Age equal to or greater than 18 years.

Exclusion Criteria:

• Pharmacological immunosuppression within the 3 months prior to the current admission date, including treatment with corticosteroids, immunosuppressive drugs (conventional or biological), or chemotherapy.
• Immunodeficiency.
• Age under 18 years.
• Absence of consent to participate in the study.

Patients with any critical illness present in the ICU of the participating hospital.