The Sepsis ClinicAl Resource And Biorepository (SCARAB) Project

Bioenergetic dysfunction is an archetypical finding in critical illness, particularly among patients with sepsis. A central feature of sepsis is the shift towards pathologic immunosuppression predisposing to secondary infections and ineffectual organ recovery. However, the extent to which metabolic abnormalities contribute to immune cell dysregulation in critically ill patients with and without sepsis remains unclear. To investigate this, we collected peripheral blood mononuclear cells (PBMCs) from medical and surgical ICU patients at Vanderbilt University Medical Center 48-72 hours after ICU admission, as well as community-matched healthy controls, with all studies conducted under IRB approval. We performed single cell RNA-sequencing using the Chromium Next GEM Single Cell 5' HT Kit v2 (10x Genomics) on a subset of 9 healthy controls, 19 ICU patients without sepsis, and 19 ICU patients with sepsis, generating a comprehensive dataset of 644,147 cells providing a detailed transcriptional map of critical illness. The ICU patient sequences are provided here; the healthy control sequences are provided in dbGaP phs004377.v1.p1.

• Study Weblinks:
  • NCBI GEO
• Study Design:
  • Case Set
• Study Type:
  • Case Set
• Total number of consented subjects: 38
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• Sequence Read Archive
• MeSH
• PMC

Inclusion Criteria:

1. Adults (≥18 years of age)
2. Admitted to the Medical or Surgical Intensive Care Unit at Vanderbilt University Medical Center (VUMC)

Exclusion Criteria:

1. Hemoglobin ≤ 7.5 g/dL, active exsanguination without hemostatic control, or contraindication to blood transfusions (e.g. Jehovah's Witness)
2. ICU stay >24 hours at VUMC or ICU stay >48 hours at an outside facility prior to enrollment
3. Cardiac arrest prior to enrollment
4. Moribund state with imminent death
5. Receiving extracorporeal membrane oxygenation (ECMO) at the time of enrollment
6. Pregnant
7. Medical trainees
8. Individuals in police custody
9. Admission to the ICU solely for frequency of nursing care
10. Admission for uncomplicated diabetic ketoacidosis, drug overdose, or alcohol withdrawal
11. Patients readmitted to the ICU after <24 hours off the unit
12. Patients enrolled in other studies that include blood draws to ensure that research blood volume limits are not exceeded
13. Receiving T cell-directed immunosuppression (e.g., tacrolimus, azathioprine, mycophenolate)
14. Receiving immunomodulatory antineoplastic therapy (e.g., pembrolizumab, ipilimumab, rituximab)
15. Severe leukopenia with insufficient PBMC yield for analysis
16. Active hematologic malignancy
17. Prior allogeneic stem cell transplant

• Primary Phenotype: Critical Illness
• Sepsis
• Immune System

• Principal Investigator
  • Julie A. Bastarache, MD. Vanderbilt University Medical Center, Nashville, TN, USA.
• Co-Investigators
  • Lorraine B. Ware, MD. Vanderbilt University Medical Center, Nashville, TN, USA.
  • Matthew T. Stier, MD, PhD. Vanderbilt University Medical Center, Nashville, TN, USA.
• Sequencing Center
  • Vanderbilt Technologies for Advanced Genomics (VANTAGE). Vanderbilt University Medical Center, Nashville, TN, USA.