Immunological imprint of COVID-19 on human peripheral blood leukocyte populations.
Immunological imprint of COVID-19 on human peripheral blood leukocyte populations.
复制标题
Covid-19的免疫学烙印在人外周血白细胞种群上。
作者：
Kratzer B;Trapin D;Ettel P;Körmöczi U;Rottal A;Tuppy F;Feichter M;Gattinger P;Borochova K;Dorofeeva Y;Tulaeva I;Weber M;Grabmeier-Pfistershammer K;Tauber PA;Gerdov M;Mühl B;Perkmann T;Fae I;Wenda S;Führer H;Henning R;Valenta R;Pickl WF
SARS-CoV-2 引发了一场大流行，目前正在夺走许多人的生命。几项研究调查了 COVID-19 感染患者在疾病期间的细胞免疫反应，但关于 COVID-19 对 COVID-19 恢复期患者的适应性和先天免疫系统可能产生的长期影响知之甚少。我们使用多参数流式细胞术分析了全外周血样本，并测定了一组感染后约 10 周患有轻度疾病的 COVID-19 康复患者 (n = 109) 和健康对照受试者 (n = 98) 中针对 S 蛋白、其 RBD 亚基和病毒核衣壳的 SARS-CoV-2 特异性抗体水平。此外，我们将免疫学变化与临床和人口统计参数相关联。即使在疾病发生十周后，COVID-19 恢复期患者的中性粒细胞也较少，而其细胞毒性 CD8+ T 细胞被激活，表现为较高的 HLA-DR 和 CD38 表达。多参数回归分析显示，在COVID-19感染的患者中，CD3+CD4+和CD3+CD8+效应记忆细胞较高，而CD25+Foxp3+T调节细胞较低。此外，COVID-19 感染患者的移行 B 细胞和浆母细胞水平均显着升高。发烧（持续时间、程度）与中央记忆 CD4+ T 细胞以及抗 S 和抗 RBD 的数量相关，但与抗 NC 抗体水平无关。此外，由 CD3+CD45RA+CD62L+CD31+ 最近胸腺移出的数量确定的“年轻免疫年龄”与味觉和/或嗅觉的丧失相关。除了诱导特异性抗体反应外，急性 SARS-CoV-2 感染还会在细胞免疫系统中留下持久的有益（即 T 细胞激活）和潜在有害（即中性粒细胞减少）印记。发病十周后，与未患 COVID-19 的受试者相比，COVID-19 患者的中性粒细胞较少，但其细胞毒性 CD8+ T 细胞仍处于激活状态。在 COVID-19 患者中，CD3+CD4+ 和 CD3+CD8+ 效应记忆细胞、移行 B 细胞和浆母细胞水平较高，而 CD25+Foxp3+ T 调节细胞水平低于未患 COVID-19 的受试者。发烧持续时间与较高数量的中央记忆 CD4+ T 细胞、抗 S 和抗 RBD 抗体水平相关，而味觉/嗅觉丧失与近期胸腺移出水平较高相关。缩写：COVID-19、2019 年冠状病毒病； ELISA，酶联免疫吸附测定； KREC，kappa 删除重组切除环； qPCR，定量PCR； RBD，SARS-CoV2刺突蛋白的受体结合域； TREC，T 细胞受体切除环； S，SARS-Cov2 的刺突蛋白； SARS-CoV-2，严重急性呼吸综合征冠状病毒 2。
SARS‐CoV‐2 has triggered a pandemic that is now claiming many lives. Several studies have investigated cellular immune responses in COVID‐19‐infected patients during disease but little is known regarding a possible protracted impact of COVID‐19 on the adaptive and innate immune system in COVID‐19 convalescent patients. We used multiparametric flow cytometry to analyze whole peripheral blood samples and determined SARS‐CoV‐2‐specific antibody levels against the S‐protein, its RBD‐subunit, and viral nucleocapsid in a cohort of COVID‐19 convalescent patients who had mild disease ~10 weeks after infection (n = 109) and healthy control subjects (n = 98). Furthermore, we correlated immunological changes with clinical and demographic parameters. Even ten weeks after disease COVID‐19 convalescent patients had fewer neutrophils, while their cytotoxic CD8+ T cells were activated, reflected as higher HLA‐DR and CD38 expression. Multiparametric regression analyses showed that in COVID‐19‐infected patients both CD3+CD4+ and CD3+CD8+ effector memory cells were higher, while CD25+Foxp3+ T regulatory cells were lower. In addition, both transitional B cell and plasmablast levels were significantly elevated in COVID‐19‐infected patients. Fever (duration, level) correlated with numbers of central memory CD4+ T cells and anti‐S and anti‐RBD, but not anti‐NC antibody levels. Moreover, a “young immunological age” as determined by numbers of CD3+CD45RA+CD62L+CD31+ recent thymic emigrants was associated with a loss of sense of taste and/or smell. Acute SARS‐CoV‐2 infection leaves protracted beneficial (ie, activation of T cells) and potentially harmful (ie, reduction of neutrophils) imprints in the cellular immune system in addition to induction of specific antibody responses. Ten weeks after disease, COVID‐19 patients had fewer neutrophils compared to subjects without COVID‐19, while their cytotoxic CD8+ T cells were still activated. In COVID‐19 patients both CD3+CD4+ and CD3+CD8+ effector memory cells, transitional B cells and plasmablast levels were higher, while CD25+Foxp3+ T regulatory cells were lower than in subjects without COVID‐19. Fever duration correlated with higher numbers of central memory CD4+ T cells, anti‐S and anti‐RBD antibody levels, while loss of taste/smell was associated with higher levels of recent thymic emigrants. Abbreviations: COVID‐19, coronavirus disease 2019; ELISA, enzyme‐linked immunosorbent assay; KRECs, kappa‐deleting recombination excision circles; qPCR, quantitative PCR; RBD, receptor‐binding domain of SARS‐CoV2 spike protein; TRECs, T‐cell receptor excision circles; S, spike protein of SARS‐Cov2; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.
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影响因子：
3.4
作者：
Boldt, Andreas;Borte, Stephan;Sack, Ulrich
通讯作者：
Sack, Ulrich
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
3.1
作者：
HAVENS, WP;MARCK, RE
通讯作者：
MARCK, RE
影响因子：
8.4
作者：
Deng, Zhifeng;Zhang, Minli;Xu, Yu
通讯作者：
Xu, Yu
DOI：
10.4269/ajtmh.1976.25.456
发表时间：
1976-01-01
影响因子：
3.3
作者：
BARTELLONI, PJ;TESH, RB
通讯作者：
TESH, RB