Around half of people with severe COVID‐19 requiring intensive care unit (ICU) treatment will survive, but it is unclear how the immune response to SARS‐CoV‐2 differs between ICU patients that recover and those that do not. We conducted whole‐blood immunophenotyping of COVID‐19 patients upon admission to ICU and during their treatment and uncovered marked differences in their circulating immune cell subsets. At admission, patients who later succumbed to COVID‐19 had significantly lower frequencies of all memory CD8+ T cell subsets, resulting in increased CD4‐to‐CD8 T cell and neutrophil‐to‐CD8 T cell ratios. ROC and Kaplan‐Meier analyses demonstrated that both CD4‐to‐CD8 and neutrophil‐to‐CD8 ratios at admission were strong predictors of in‐ICU mortality. Therefore, we propose the use of the CD4‐to‐CD8 T cell ratio as a marker for the early identification of those individuals likely to require enhanced monitoring and/or pro‐active intervention in ICU.

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Myeloid‐derived suppressor cells (MDSCs) are important regulators of immune processes during sepsis in mice. However, confirming these observations in humans has been challenging due to the lack of defined preparation protocols and phenotyping schemes for MDSC subsets. Thus, it remains unclear how MDSCs are involved in acute sepsis and whether they have a role in the long‐term complications seen in survivors. Here, we combined comprehensive flow cytometry phenotyping with unsupervised clustering using self‐organizing maps to identify the three recently defined human MDSC subsets in blood from severe sepsis patients, long‐term sepsis survivors, and age‐matched controls. We demonstrated the expansion of monocytic M‐MDSCs and polymorphonuclear PMN‐MDSCs, but not early‐stage (e)‐MDSCs during acute sepsis. High levels of PMN‐MDSCs were also present in long‐term survivors many months after discharge, suggesting a possible role in sepsis‐related complications. Altogether, by employing unsupervised clustering of flow cytometric data we have confirmed the likely involvement of human MDSC subsets in acute sepsis, and revealed their expansion in sepsis survivors at late time points. The application of this strategy in future studies and in the clinical/diagnostic context would enable rapid progress toward a full understanding of the roles of MDSC in sepsis and other inflammatory conditions.