Classical monocytes-low expressing HLA-DR is associated with higher mortality rate in SARS-CoV-2+ young patients with severe pneumonia.

Aims: This study aimed to investigate whether monocyte dysregulation and hyperinflammation serve as predictive markers for mortality in young patients with SARS-CoV-2 severe pneumonia. Methods: A prospective cohort study was conducted in a tertiary-level public University Hospital in Colombia. Forty young adults (18-50 years of age) with severe pneumonia and SARS-CoV-2 infection confirmed by qPCR, were enrroled. Serum cytokines and the monocyte phenotype profile, including PDL1/HLA-DR expression, were determined during the first 24 h of hospitalization. Routine laboratory parameters were measured throughout patient follow-up until either death or hospital discharge. We also included a cohort of twenty-five healthy control subjects. Key findings: Elevated levels of IL-10, IL-8, and IL-6 cytokines emerged as robust predictors of mortality in young adults with severe pneumonia due to SARS-CoV-2 infected. A descriptive analysis revealed a cumulative mortality rate of 30 % in unvaccinated and ICU-admitted patients. Patients who died had significantly lower expression of HLA-DR on their classical monocytes subsets (CD14 Significance: The early reduction in HLA-DR expression within classical monocytes emerged as an independent predictor of mortality, irrespective of comorbidities. Together with PD-L1 expression and cytokine alterations, these findings support the notion that monocyte immunosuppression plays a fundamental role in the pathogenesis and mortality of young patients infected with SARS-CoV-2. These findings hold significant implications for risk assessment and therapeutic strategies in managing critically ill young adults with SARS-CoV-2 infection.