Correlation of Memory CD8+ T Cells With Sepsis Severity and Mortality: a Single-center, Unblinded, Prospective, Non-interventional, Observational Study

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology16 enrolled

Overview

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Sustained excessive inflammation and immune dysfunction have been confirmed to play a key role in organ damage and early death of sepsis patients. Therefore, it is important to reduce excessive inflammatory response mediated by immune cells and pro-inflammatory cytokines in the acute phase of sepsis. Single-cell RNA sequencing performed on both septic patients and mice suggest that changes in Tcm (CD3+ CD8+ CD44+ CD127+ CD62L+) and Tem (CD3+ CD8+ CD44+ CD127+ CD62L -) in the acute phase of sepsis may play an important role in sepsis. In addition, animal researches showed that Tcm and Tem decreased decreased continuously at 24, 48 and 72h after cecal ligation and perforation (CLP) in mice, and the adoptive transfer of Tcm , sorting from spleen of mice 24h after CLP , but not Tem improved 7-day survival rate of sepsis mice. This observational study is aimed to investigate the quantity and proliferation of Tcm and Tem in the acute phase of sepsis and their correlation with severity level and mortality of septic patients in ICU.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Sepsis Inflammatory Response

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Patients aged 18-60 years old without restriction of gender, race, religion, creed or nationality; No sedative drugs with elimination half-life were used before inclusion in the study; Patients and/or their family members know and agree to participate in the trial. Exclusion Criteria: History of solid organ or bone marrow transplantation; Diseases that may affect immune-related indicators, such as autoimmune diseases such as rheumatoid arthritis and SLE, or hematological malignancies such as leukemia and lymphoma; Have received radiotherapy or chemotherapy within the past 30 days, or have received immunosuppressive drugs (tripterygium, mycophenolate, cyclophosphamide, FK506, etc); Pregnancy or lactation; Chronic nephrosis; Severe chronic liver disease (child-Pugh: Grade C); alcohol or opioid dependence, mental illness, or severe cognitive impairment; Patients and/or their family members refuse to participate in the trial.

Outcomes

Primary Outcomes

Absolute number of CD8+T subsets in the peripheral blood (0 hour)

CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells

Time frame: 0 hour after study inclusion

Absolute number of CD8+T subsets in the peripheral blood (24 hours)

CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells

Time frame: 24 hours after study inclusion

Absolute number of CD8+T subsets in the peripheral blood (48 hours)

CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells

Time frame: 48 hours after study inclusion

Absolute number of CD8+T subsets in the peripheral blood (72 hours)

CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells，and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells

Time frame: 72 hours after study inclusion

proliferation of CD8+T subsets in the peripheral blood (0 hour)

expression of Ki67 in Tcm and Tem

Time frame: 0 hour after study inclusion

proliferation of CD8+T subsets in the peripheral blood (24 hours)

expression of Ki67 in Tcm and Tem

Time frame: 24 hours after study inclusion

proliferation of CD8+T subsets in the peripheral blood (48 hours)

expression of Ki67 in Tcm and Tem

Time frame: 48 hours after study inclusion

proliferation of CD8+T subsets in the peripheral blood (72 hours)

expression of Ki67 in Tcm and Tem

Time frame: 72 hours after study inclusion

ICU length of stay

Length of stay in the ICU

Time frame: up to 4 weeks

PD-1 expression of CD8+T subsets in the peripheral blood (24 hours)

expression of PD-1 in Tcm and Tem

Time frame: 24 hours after study inclusion

Secondary Outcomes

Mechanical ventilation time after inclusion

Patients requiring mechanical ventilation after study inclusion

Time frame: up to 4 weeks

Total hospital length of stay

Total length of hospital stay

Time frame: up to 4 weeks

In-hospital mortality

Mortality rates for the entire period of hospitalization

Time frame: up to 4 weeks

90-day readmission rate

Percentage of readmission to hospital within 90 days of study inclusion

Time frame: up to 4 weeks

Infection complications

Pulmonary infection, urinary tract infection, bloodstream infections, etc

Time frame: up to 4 weeks

Acute physiology and chronic health evaluation (APACHE) Ⅱ score

0-67, higher scores correspond to more severe disease and a higher risk of death

Time frame: 0h after study inclusion

Acute physiology and chronic health evaluation (APACHE) Ⅱ score

0-67, higher scores correspond to more severe disease and a higher risk of death

Time frame: 24 hours after study inclusion

Acute physiology and chronic health evaluation (APACHE) Ⅱ score

0-67, higher scores correspond to more severe disease and a higher risk of death

Time frame: 48 hours after study inclusion

Acute physiology and chronic health evaluation (APACHE) Ⅱ score

0-67, higher scores correspond to more severe disease and a higher risk of death

Correlation of Memory CD8+ T Cells With Sepsis Severity and Mortality: a Single-center, Unblinded, Prospective, Non-interventional, Observational Study

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes