The aim of this investigation is to longitudinally quantify host gene expression and serum proteins in children with infectious and non-infectious SIRS. The investigators hypothesize that children with non-infectious SIRS, with bacterial infection associated SIRS, or with viral infection associated SIRS will exhibit distinct patterns of host gene expression and serum proteins. The investigators further hypothesize that it should be possible to discover sets of mRNA or protein biomarkers that will permit unambiguous diagnosis of non-infectious SIRS, SIRS associated with bacterial infection, and SIRS associated with viral infection.

The investigators will undertake a proof-of-concept, pilot, prospective, observational trial that aims to recruit ~90 children from the Seattle Children's Hospital Pediatric Intensive Care Unit (PICU) and Cardiac Intensive Care Unit (CICU). The study will plan to recruit 30 children who are scheduled for surgery to repair congenital cardiac malformations, 15 - 25 immunocompetent children with culture positive sepsis, and 15 - 25 immunocompromised children with culture positive sepsis, and 30-40 children who are polymerase chain reaction (PCR) positive for viral respiratory pathogens (RSV, influenza, parainfluenza, rhinovirus, etc), and who meet the eligibility criteria. In total, accounting for culture negative bacterial sepsis (estimated 40%), the investigators plan to enroll 50 children with sepsis, 30-40 with viral sepsis, and 20 children undergoing surgery for congenital heart disease.

Demographic data will be collected at the time of ICU admission. Illness severity will be quantified by PRISM III and day 1 PELOD scores. Additional measures of sepsis severity will include oxygenation index, saturation index and duration of mechanical ventilation, vasoactive inotropic score and duration of vasoactive-inotropic support and highest serum creatinine on day 1. Resource utilization will be measured as PICU and hospital duration of stay.

For all children enrolled in the study, blood samples will be obtained on study days 1, 2 and 3. For children with sepsis, if cultures remain sterile or PCR negative, no additional research blood samples will be obtained. For children with sepsis and a positive culture or positive PCR by study day 3, additional blood samples will be obtained on the day of PICU discharge.

A. INSI group: systemic inflammation, in the absence of culture positive infection. Cardiac surgery patients, n=30.

Inclusion Criteria:

• Admission to the CICU AND
• Age ~1-18 years AND
• Weight exceeding 10 kg
• Vascular catheter capable of providing the blood draw or anticipated orders for venipuncture for clinical labs AND
• Status post open heart surgery requiring cardiopulmonary bypass AND
• Parents speak English AND
• Not previously enrolled in the GAPPSS investigation

Exclusion Criteria:

• Pre- or post-operative culture positive infection OR
• Not expected to survive the CICU stay OR
• Ward of the state OR
• Concurrent malignancy or autoimmune disorder

B. CSSS (Clinical Severe Sepsis Syndrome) group: systemic inflammation, in the presence of highly suspected or documented bacterial infection. Children with clinical severe sepsis, n = 40. In this group, the investigators will enroll children who are immunocompetent as well as children who are immunocompromised.

Inclusion Criteria:

• Admitted to the PICU AND
• Age newborn (>38 weeks EGA)-18 years AND
• Weight equal to or greater than 4 kg AND
• Vascular catheter capable of providing the blood draw or anticipated orders for venipuncture for clinical labs AND
• At least one organ dysfunction (severe sepsis) AND
• Parents speak English AND
• SIRS (systemic inflammatory response syndrome) AND
• Strongly suspected or documented source of infection
• Not previously enrolled in the GAPPSS investigation

Exclusion Criteria:

• PICU nosocomial primary infection accounting for the sepsis event
• Not expected to survive the PICU stay
• Ward of the state

C. Viral Infection group. Severe respiratory dysfunction in the presence of PCR -documented viral infection. Children with clinical severe viral sepsis, n=6. In this group, the investigators will enroll children who are immunocompetent as well as children who are immunocompromised.

Inclusion Criteria:

• Admitted to the PICU AND
• Age newborn (>38 weeks EGA)-18 years AND
• Weight equal to or greater than 4 kg AND
• Vascular catheter capable of providing the blood draw or anticipated orders for venipuncture for clinical labs AND
• Parents speak English AND
• Severe respiratory dysfunction requiring invasive or non-invasive positive pressure mechanical ventilation support AND
• Positive PCR verifying a viral infection
• Not previously enrolled in the GAPPSS investigation

Exclusion Criteria:

• PICU nosocomial primary infection accounting for the sepsis event
• Not expected to survive the PICU stay
• Ward of the state

INSI group: children who had congenital cardiac defect corrective surgery requiring cardiopulmonary bypass, known to induce an INSI response for ~24 hours thereafter. All children in this group were immune competent and culture negative.

CSSS group: children with confirmed or highly suspected infection (microbial culture orders, antimicrobial prescription), SIRS criteria (including fever/hypothermia and leukocytosis/leukopenia), and at least cardiovascular ± pulmonary organ dysfunction.

Viral Infection group: children with severe respiratory dysfunction in the presence of PCR -documented viral infection.

The investigators plan to publish the results of the GAPPSS study in a peer-reviewed scientific journal. A supplemental digital file associated with this paper will be made publicly available through a web link, and will contain relevant clinical data (with all patients de-identified).