Sepsis is a life-threatening dysregulated immune response to infection associated with multi-organ failure and a high mortality rate.While researchers have focused mainly on acute sepsis, post-sepsis care of survivors has long been neglected despite the observation that many sepsis survivors suffer from debilitating post-sepsis syndrome. This syndrome is characterized by frequent hospital readmissions and increased mortality due to persistent immune dysfunction, cardiovascular disease, and cognitive impairment, causing poor quality of life and a substantial burden on the healthcare system. Disconcertingly, the number of sepsis survivors at risk for hospital readmission continues to rise.7 Of the post-sepsis symptoms, post-sepsis immunosuppression is perhaps the most clinically important. While sepsis presents as an initial phase of hyperinflammation (a "cytokine storm"), it is followed by an immunosuppressive phase that is now understood to last weeks to months and predisposes survivors to lethal secondary infections and sepsis recurrence. A third of deaths eight years post-sepsis are caused by recurrent sepsis.We hypothesize that changes in the transcriptome and DNA methylome in immune cells of survivors might be the underlying driver for prolonged immunosuppression, and may also be correlated with long-term morbidity and mortality post-sepsis, as well as other symptoms of post-sepsis syndrome including PTSD and cardiovascular disease.

Inclusion criteria sepsis group:

• Adult patients, aged between 18 and 85 years
• Able to provide informed consent themselves or informed consent can be obtained via next of kin or legal guardian
• Included in Acutelines, where blood sample was drawn upon ED admission
• Satisfy the Sepsis-3 criteria for sepsis (Figure 2), combined with clinical suspicion of infection and/or fever (body temperature > 38.5°C)
• Survive at 3 months post discharge
• Inclusion criteria control group:Adult patients, aged between 18 and 85 years
• Able to provide informed consent themselves or informed consent can be obtained via next of kin or legal guardian
• Included in Acutelines, where blood sample was drawn upon ED admission
• Non-infectious reason of admission (specifically syncope, electrolyte disturbance, intoxication, gastro-intestinal bleeding)

4.3 Exclusion criteria

The participants should not meet any of the following exclusion criteria:

• Transfer from another hospital
• Emergency room visit in connection with accidental exposure of bodily material to patient ("needle stick injury")
• Visit an emergency room in connection with organ transplantation
• Discharged home without hospital admittance after ED visit
• Unable to give blood
• Immunosuppressive therapies such as corticosteroids (>10mg) or small molecule immune suppressants within the last three months, or biologicals administered within the last year
• Radiotherapy or systemic chemotherapy within the last three months
• Known pregnancy; the presence of pregnancy will be verified by asking the potential participant
• A hospitalization of more than 21 days

Patients between 18-85 years old admitted to the emergency department (ED) of the University Medical Center Groningen (UMCG) with suspected sepsis according to the sepsis-3 criteria who survive their ED admission at three months. A control group will compose of age and sex-matched ED patients admitted for non-infectious causes. Both the septic patients and controls have already been enrolled in the Acutelines study.