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

Juan Sebastián Henao-Agudelo; Sebastian Ayala; Marisol Badiel; Andrés F Zea-Vera; Lorena Matta Cortes

doi:10.1016/j.heliyon.2024.e24099

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

Heliyon. 2024 Jan 9;10(2):e24099. doi: 10.1016/j.heliyon.2024.e24099. eCollection 2024 Jan 30.

Authors

Juan Sebastián Henao-Agudelo¹, Sebastian Ayala^{2

3}, Marisol Badiel^{2

3}, Andrés F Zea-Vera^{4

5}, Lorena Matta Cortes^{2

3}

Affiliations

¹ Faculty of Health Sciences, Unidad Central del Valle del Cauca, Tuluá, Colombia.
² Department of Internal Medicine, Universidad del Valle, Cali, Colombia.
³ Hospital Universitario del Valle Evaristo García, Cali, Colombia.
⁴ School of Basic Sciences, Universidad del Valle, Cali, Colombia.
⁵ LCIM//Division of Intramural Research, NIAID, National Institutes of Health, Bethesda, MD, USA.

Abstract

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⁺CD16^-) than survivors and healthy controls. Lower expression of HLA-DR was associated with greater clinical severity (APACHE≥12) and bacterial coinfection (relative risk 2.5 95%CI [1.18-5.74]). Notably, the expression of HLA-DR in 27.5 % of CD14⁺/CD16^- monocytes was associated with a significantly lower probability of survival.

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.

Keywords: COVID-19; HLA-DR; Monocytes; PD-L1; Pneumonia; SARS-CoV-2; Young adults.