Immunoparalysis is a significant concern in patients with sepsis and critical illness, potentially leading to increased risk of secondary infections. This study aimed to perform a longitudinal assessment of immune function over the initial two weeks following the onset of sepsis and critical illness. We compared ex vivo stimulated cytokine release to traditional markers of immunoparalysis, including monocyte Human Leukocyte Antigen (mHLA)-DR expression and absolute lymphocyte count (ALC). A total of 64 critically ill patients were recruited in a tertiary care academic medical setting, including 31 septic and 33 non-septic patients. Results showed that while mHLA-DR expression significantly increased over time, this was primarily driven by the non-septic subset of critically ill patients. ALC recovery was more prominent in septic patients. Ex vivo stimulation revealed significant increases in TNF and IL-6 production over time in septic patients. However, IFNγ production varied with the stimulant used and did not show significant recovery when normalized to cell count. No significant correlation was found between mHLA-DR expression and other immunoparalysis biomarkers. These findings suggest the need for more nuanced immune monitoring approaches beyond the traditional ‘sepsis’ versus ‘non-sepsis’ classifications in critically ill patients. It also provided further evidence of a potential window for targeted immunotherapeutic interventions in the first week of critical illness.

The authors have declared no competing interest.

National Institute of General Medical Sciences, grant number R35GM150695 (ASB).

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IRB (Human Subjects Protection Office) of Penn State Hershey Medical Center gave ethical approval for this work

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