Centre for Primary Immunodeficiencies, Clinic of Pneumology and Phthisiology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin University Hospital, Martin, Slovakia.
Department of Clinical Immunology and Allergology, Martin University Hospital, Martin, Slovakia.
Front Immunol. 2022 Mar 14;13:861666. doi: 10.3389/fimmu.2022.861666. eCollection 2022.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an appropriate function of the immune system is important for a rapid clearance of the virus, progression to the severe and critical phases of the disease is related to an exaggerated immune response associated with a cytokine storm. We analyzed differences and longitudinal changes in selected immune parameters in 823 adult COVID-19 patients hospitalized in the Martin University Hospital, Martin, Slovakia. Examined parameters included the differential blood cell counts, various parameters of cellular and humoral immunity (serum concentration of immunoglobulins, C4 and C3), lymphocyte subsets (CD3, CD4, CD8, CD19, NK cells, CD4CD45RO), expression of activation (HLA-DR, CD38) and inhibition markers (CD159/NKG2A). Besides already known changes in the differential blood cell counts and basic lymphocyte subsets, we found significantly higher proportion of CD8CD38 cells and significantly lower proportion of CD8NKG2A and NK NKG2A cells on admission in non-survivors, compared to survivors; recovery in survivors was associated with a significant increase in the expression of HLA-DR and with a significant decrease of the proportion of CD8CD38cells. Furthermore, patients with fatal outcome had significantly lower concentrations of C3 and IgM on admission. However, none of the examined parameters had sufficient sensitivity or specificity to be considered a biomarker of fatal outcome. Understanding the dynamic changes in immune profile of COVID-19 patients may help us to better understand the pathophysiology of the disease, potentially improve management of hospitalized patients and enable proper timing and selection of immunomodulator drugs.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在过去 2 年在全球范围内传播，已导致全球超过 2.6 亿人感染，并给医疗保健系统带来了沉重负担。已经确定了一些与不良结局相关的危险因素，包括老年、选定的合并症、免疫抑制以及实验室标志物。免疫系统在 SARS-CoV-2 感染的病理生理学中的作用是不可否认的：虽然免疫系统的适当功能对于快速清除病毒很重要，但疾病向严重和危急阶段的进展与过度的免疫反应相关，这种免疫反应与细胞因子风暴有关。我们分析了在斯洛伐克马汀大学医院住院的 823 名成年 COVID-19 患者的选定免疫参数的差异和纵向变化。检查的参数包括白细胞分类计数、细胞和体液免疫的各种参数（血清免疫球蛋白、C4 和 C3 浓度）、淋巴细胞亚群（CD3、CD4、CD8、CD19、NK 细胞、CD4+CD45RO）、表达激活（HLA-DR、CD38）和抑制标志物（CD159/NKG2A）。除了已经知道的白细胞分类计数和基本淋巴细胞亚群的变化外，我们还发现非幸存者入院时 CD8+CD38 细胞的比例明显更高，而 CD8+NKG2A 和 NK NKG2A 细胞的比例明显更低；幸存者的恢复与 HLA-DR 的表达显著增加以及 CD8+CD38 细胞比例的显著降低有关。此外，死亡患者入院时 C3 和 IgM 的浓度明显较低。然而，检查的参数都没有足够的敏感性或特异性来作为死亡结局的生物标志物。了解 COVID-19 患者免疫谱的动态变化可能有助于我们更好地了解疾病的病理生理学，有可能改善住院患者的管理，并能够适当选择和使用免疫调节剂药物。
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