Abstract：
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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 CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non-class-switched CD19+IgD+CD27+ 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 CD3-CD56+ NK and CD19+CD27+ 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.
CONCLUSIONS: 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.
METHODS: 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).
RESULTS: 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 CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non-class-switched CD19+IgD+CD27+ 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 CD3-CD56+ NK and CD19+CD27+ 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.
CONCLUSIONS: 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.
摘要：
背景：SARS-CoV-2已引发大流行，并导致长期发病率。一些研究已经调查了急性感染期间的即时细胞和体液免疫应答。然而,关于COVID-19对免疫系统的长期影响知之甚少。
方法：我们对106名未接种疫苗的受试者在首次SARS-CoV-2感染后10周（10w）和10个月（10m）的细胞和体液免疫参数进行了纵向研究。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。Spike蛋白（S）特异性抗体，测定受体结合域(RBD)和核衣壳蛋白(NC)。将感染后10w和10m测量的所有参数与匹配的参数进行比较，未感染对照组（n=98）。
结果：全血流式细胞仪分析显示，与对照组相比，COVID-19后10m，恢复期患者的绝对粒细胞减少，单核细胞,和淋巴细胞计数，涉及T，B,和NK细胞，特别是CD3+CD45RA+CD62L+CD31+近期胸腺外移T细胞和非类别转换CD19+IgD+CD27+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相关。NC和S特异性抗体水平的强烈下降与年龄较小有关（到10.3岁，p<.01)和较少的CD3-CD56+NK和CD19+CD27+B记忆细胞。10μm时T细胞亚群的变化，如效应子和Treg数量的归一化，RTE下降，中枢记忆T细胞数量的增加与抗体下降模式无关。
结论：COVID-19导致先天和适应性免疫细胞的长期减少，这与Th2血清细胞因子谱有关。这可能为COVID-19后的长期后遗症提供了免疫学机制。
方法：我们对106名未接种疫苗的受试者在首次SARS-CoV-2感染后10周（10w）和10个月（10m）的细胞和体液免疫参数进行了纵向研究。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。Spike蛋白（S）特异性抗体，测定受体结合域(RBD)和核衣壳蛋白(NC)。将感染后10w和10m测量的所有参数与匹配的参数进行比较，未感染对照组（n=98）。
结果：全血流式细胞仪分析显示，与对照组相比，COVID-19后10m，恢复期患者的绝对粒细胞减少，单核细胞,和淋巴细胞计数，涉及T，B,和NK细胞，特别是CD3+CD45RA+CD62L+CD31+近期胸腺外移T细胞和非类别转换CD19+IgD+CD27+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相关。NC和S特异性抗体水平的强烈下降与年龄较小有关（到10.3岁，p<.01)和较少的CD3-CD56+NK和CD19+CD27+B记忆细胞。10μm时T细胞亚群的变化，如效应子和Treg数量的归一化，RTE下降，中枢记忆T细胞数量的增加与抗体下降模式无关。
结论：COVID-19导致先天和适应性免疫细胞的长期减少，这与Th2血清细胞因子谱有关。这可能为COVID-19后的长期后遗症提供了免疫学机制。
