Aging is associated with immunosenescence and impaired host defense mechanisms, contributing to influenza-related morbidity and mortality. Preliminary data demonstrate that the platelet transcriptome is markedly different between healthy subjects and influenza patients. Interferon-induced transmembrane proteins (IFITM) family members are among the transcripts significantly increased in platelets during influenza and expression of IFITM-3 is impaired in elderly subjects, a pattern associated with increased mortality. This study will build on these data and investigate if aging influences the expression of platelet IFITM family members in patients with influenza and sepsis.

This study will prospectively determine if aging alters the induction of (IFITMs) in platelets from hospitalized influenza and sepsis patients. The study will also determine if diminished expression of IFITM family members correlates with an increased risk of adverse outcomes in older influenza and sepsis patients.

This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.

Inclusion Criteria:

• ≥18 years old at the time of enrollment
• Meet one of the following three main criteria:

A. INFLUENZA (AND OTHER RESPIRATORY VIRUS) PATIENTS:

Patients admitted to the intensive care unit (ICU) with a primary microbiologic diagnosis of influenza (any strain) or other routinely clinically identified respiratory viruses within 1 week of symptom onset. Influenza or other respiratory virus will be diagnosed using an RT-PCR viral panel on a respiratory tract specimen, as is currently standard of care on patients admitted to the ICUs at IMC with respiratory symptoms.

OR

B. SEPSIS PATIENTS:

Sepsis patients must have

1. Suspected or confirmed infection

   AND

2. Organ dysfunction as defined by a SOFA >= 2 above baseline (if no baseline data available, SOFA assumed to be 0)

OR

C. SEPTIC SHOCK PATIENTS:

AFTER INFUSION OF 20ML/KG CRYSTALLOID OR EQUIVALENT, Septic shock patients must have

1. Suspected or confirmed infection

   AND

2. Lactate > 2 mmol/L

   AND

3. Receiving vasopressors

   • All patients must be enrolled into the study within 72 hours of ICU admission

Exclusion criteria

• Have a congenital or acquired immunodeficiency disorder (e.g., chronic variable immune deficiency, agammaglobulinemia, hypogammaglobulinemia, leukocyte adhesion defects, IgA deficiency, etc.)
• Have neutropenia (<1,000/mm3)
• Have received immunosuppressant medications within the previous 30 days (e.g., prednisone or prednisone equivalent at a dose≥10mg daily for ≥14 days or any cyclosporine, TNF-alpha antagonists, tacrolimus, sirolimus, interferons, mycophenolate, biological agents, methotrexate, azathioprine, polyclonal/monoclonal antibodies, etc.)
• Have any history of bone marrow or organ transplantation
• Have an active malignancy (not including non-melanoma skin cancer or localized prostate cancer), or have received chemotherapy drugs within the last 6 months.
• Have been admitted to the ICU for greater than 72 hours
• Have a Hemoglobin level <7gm/dl
• Have clinically significant bleeding

This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.