Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
Center for Pathophysiology, Infectiology and Immunology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
Allergy. 2024 Sep;79(9):2482-2501. doi: 10.1111/all.16210. Epub 2024 Jul 14.
SARS-CoV-2 has triggered a pandemic and contributes to long-lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long-term effects of COVID-19 on the immune system.
We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non-vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS-CoV-2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor-binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98).
Whole blood flow cytometric analyses revealed that 10 m after COVID-19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3CD45RACD62LCD31 recent thymic emigrant T cells and non-class-switched CD19IgDCD27 memory B cells. Cellular changes were associated with a reversal from Th1- to Th2-dominated serum cytokine patterns. Strong declines of NC- and S-specific antibody levels were associated with younger age (by 10.3 years, p < .01) and fewer CD3CD56 NK and CD19CD27 B memory cells. Changes of T-cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern.
COVID-19 causes long-term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long-term sequelae after COVID-19.
SARS-CoV-2 引发了大流行，并导致长期发病。几项研究调查了急性感染期间的即刻细胞和体液免疫反应。然而，人们对 COVID-19 对免疫系统的长期影响知之甚少。
我们对 106 名未接种疫苗的受试者进行了一项纵向研究，这些受试者在首次感染 SARS-CoV-2 后 10 周（10w）和 10 个月（10m）时进行了细胞和体液免疫参数检测。通过多参数流式细胞术分析外周血免疫细胞，通过多重技术检测血清细胞因子。测定针对 Spike 蛋白（S）、受体结合域（RBD）和核衣壳蛋白（NC）的抗体。将感染后 10w 和 10m 时测量的所有参数与匹配的未感染对照组（n=98）进行比较。
全血流式细胞术分析显示，COVID-19 后 10m，与对照组相比，恢复期患者的绝对粒细胞、单核细胞和淋巴细胞计数减少，涉及 T、B 和 NK 细胞，特别是 CD3CD45RACD62LCD31 近期胸腺迁出 T 细胞和非类别转换 CD19IgDCD27 记忆 B 细胞。细胞变化与从 Th1 到 Th2 主导的血清细胞因子模式的逆转有关。NC-和 S-特异性抗体水平的强烈下降与年龄较小（10.3 岁，p<0.01）和较少的 CD3CD56 NK 和 CD19CD27 B 记忆细胞有关。10m 时 T 细胞亚群的变化，如效应细胞和 Treg 数量的正常化、RTE 的下降和中央记忆 T 细胞数量的增加，与抗体下降模式无关。
COVID-19 导致固有和适应性免疫细胞长期减少，这与 Th2 血清细胞因子谱有关。这可能为 COVID-19 后长期后遗症提供一种免疫学机制。
