Reduced monocytic HLA-DR expression indicates immunosuppression in critically ill COVID-19 patients.

BACKGROUND: The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes / macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human leukocyte antigen-DR (mHLA-DR) expression within the major histocompatibility complex class II reflects a state of immunosuppression, also referred to as injury-associated immunosuppression. As the role of immunosuppression in coronavirus disease 2019 (COVID-19) disease is currently unclear, we seek to explore the level of mHLA-DR expression in COVID-19 patients. METHODS: In a preliminary prospective monocentric observational study, 16 COVID-19 positive patients (75% male, median age: 68 [interquartile range 59-75], APACHE-II score in 9 ICU patients: 30 [interquartile range 25-32] with acute respiratory failure were included. Standardized quantitative assessment of mHLA-DR on CD14+ cells was performed using calibrated flow cytometry at baseline (ICU admission), and at days 3 and 5 after ICU admission. Baseline data was compared to hospitalized non-critically ill COVID-19 patients. RESULTS: While normal mHLA-DR expression was observed in all hospitalized non-critically ill patients (n=7), 89% (8/9) critically ill patients with COVID-19- induced acute respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. Monocytic HLA-DR expression at admission was significantly lower in critically ill patients (median, [quartiles]: 9280 antibodies/cell [6114, 16567]) as compared to the non-critically ill patients (30900 antibodies/cell [26777, 52251]), with a median difference of 21508 antibodies/cell (95% CI: 14118 to 42971), P=0.002. Reduced monocytic HLA-DR expression was observed to persist until day 5 after ICU admission. CONCLUSIONS: When compared to non-critically ill hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, indicating a dysfunctional immune response. This immunosuppressive (monocytic) phenotype remained unchanged over the ensuing days after ICU admission. Strategies aiming for immunomodulation in this population of critically ill patients should be guided by an immune-monitoring program in an effort to determine who might benefit best from a given immunological intervention.