Monneret Guillaume, Voirin Nicolas, Richard Jean-Christophe, Cour Martin, Rimmelé Thomas, Garnier Lorna, Yonis Hodane, Coudereau Remy, Gossez Morgane, Malcus Christophe, Wallet Florent, Delignette Marie-Charlotte, Dailler Frederic, Buisson Marielle, Argaud Laurent, Lukaszewicz Anne-Claire, Venet Fabienne
Immunology Laboratory, Hospices Civils de Lyon, Edouard Herriot Hospital, 5 Place d'Arsonval, 69437, Lyon, France.
EA 7426 "Pathophysiology of Injury-Induced Immunosuppression", Joint Research Unit HCL-bioMérieux, (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), 69003, Lyon, France.
Ann Intensive Care. 2024 May 18;14(1):76. doi: 10.1186/s13613-024-01310-5.
A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented.
To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30-6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09-4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72-13.57), p = 0.001).
By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.
10天的地塞米松治疗方案已成为国际上采用的重症COVID-19患者的标准治疗方法。然而，由SARS-CoV-2感染引发的免疫反应仍然是一个复杂且动态的现象，导致各种免疫特征和轨迹。地塞米松治疗结束后重症COVID-19患者的免疫状态尚未得到充分记录。
为了分析地塞米松疗程后重症COVID-19患者的单核细胞HLA-DR表达（mHLA-DR）和CD4 + T淋巴细胞计数（CD4），并评估它们与28天ICU死亡率的关联，纳入了入住ICU至少10天且接受地塞米松治疗的成年COVID-19患者（n = 176）。评估了入住ICU后第10天测量的每个生物标志物值（或联合）与ICU中28天死亡率之间的关联。在第10天，大多数患者的这两个参数值均下降。观察到低mHLA-DR与28天死亡率之间存在显著关联。在包括年龄、合并症或既往免疫抑制的多变量分析中，这种关联仍然显著（调整后的危险比（aHR）= 2.86 [1.30 - 6.32]，p = 0.009）。CD4 + T细胞计数降低也得到了类似结果（aHR = 2.10 [1.09 - 4.04]，p = 0.027）。当将这些生物标志物联合起来时，mHLA-DR降低且CD4低的患者28天死亡率的独立且显著风险升高（即60%，aHR = 4.83 (1.72 - 13.57)，p = 0.001）。
通过使用临床实践中可用的标准化免疫监测工具，可以识别出在10天地塞米松治疗结束时具有高死亡风险的患者亚组。这强调了将免疫监测纳入重症监护患者监测以指导进一步免疫调节方法的重要性。
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