Henao-Agudelo Juan Sebastián, Ayala Sebastian, Badiel Marisol, Zea-Vera Andrés F, Matta Cortes Lorena
Faculty of Health Sciences, Unidad Central del Valle del Cauca, Tuluá, Colombia.
Department of Internal Medicine, Universidad del Valle, Cali, Colombia.
Heliyon. 2024 Jan 9;10(2):e24099. doi: 10.1016/j.heliyon.2024.e24099. eCollection 2024 Jan 30.
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.
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.
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 (CD14CD16) 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.
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.
本研究旨在调查单核细胞失调和炎症反应过度是否可作为新型冠状病毒2型(SARS-CoV-2)重症肺炎年轻患者死亡率的预测指标。
在哥伦比亚一家三级公立大学医院进行了一项前瞻性队列研究。纳入了40名经定量聚合酶链反应(qPCR)确诊为重症肺炎且感染SARS-CoV-2的年轻成年人(18至50岁)。在住院的头24小时内测定血清细胞因子和单核细胞表型谱,包括程序性死亡受体配体1(PDL1)/人类白细胞抗原-DR(HLA-DR)表达。在患者整个随访期间测量常规实验室参数,直至死亡或出院。我们还纳入了25名健康对照者。
白细胞介素-10(IL-10)、白细胞介素-8(IL-8)和白细胞介素-6(IL-6)细胞因子水平升高是感染SARS-CoV-2的重症肺炎年轻成年人死亡率的有力预测指标。描述性分析显示,未接种疫苗且入住重症监护病房(ICU)的患者累积死亡率为30%。死亡患者经典单核细胞亚群(CD14CD16)上HLA-DR的表达明显低于幸存者和健康对照者。HLA-DR表达降低与更高的临床严重程度(急性生理与慢性健康状况评分系统Ⅱ[APACHEⅡ]≥12)和细菌合并感染相关(相对风险2.5,95%置信区间[1.18 - 5.74])。值得注意的是,27.5%的CD14/CD16单核细胞中HLA-DR的表达与显著较低的生存概率相关。
经典单核细胞内HLA-DR表达的早期降低是死亡率的独立预测指标,与合并症无关。连同程序性死亡受体1(PD-L1)表达和细胞因子改变,这些发现支持单核细胞免疫抑制在感染SARS-CoV-2的年轻患者发病机制和死亡率中起重要作用的观点。这些发现对管理感染SARS-CoV-2的重症年轻成年人的风险评估和治疗策略具有重要意义。