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恢复期 COVID-19 狼疮患者的体液和细胞反应。

Humoral and cellular response in convalescent COVID-19 lupus patients.

机构信息

Department of Rheumatology, Lupus Unit, Hospital Universitari Vall d´Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d´Hebron 119-129, 08035, Barcelona, Spain.

Clinical Pharmacology Service, Department of Pharmacology, Therapeutics and Toxicology, Fundació Institut Català de Farmacologia, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, 08035, Barcelona, Spain.

出版信息

Sci Rep. 2022 Aug 12;12(1):13787. doi: 10.1038/s41598-022-17334-5.

Abstract

In SLE, underlying immune dysregulation and immunosuppression may increase the susceptibility to COVID-19 and impair the humoral and adaptive response. We aimed to characterize COVID-19 infection, identifying susceptibility and severity risk factors, assessing the presence of SARS-CoV-2 IgG antibodies and analyzing the cellular response. We established a prospective cohort of lupus patients to estimate the COVID-19 incidence compared to the reference general population. Data were collected via telephone interviews and medical record review. SARS-CoV-2 IgG antibodies were measured cross-sectionally as part of routine surveillance. Longitudinal changes in antibody titers and immunological profile from convalescent COVID-19 patients were evaluated at 6, 12 and 24 week after symptom onset. From immunological studies, PBMCs from convalescent patients were extracted and analyzed by flow cytometry and gene expression analysis. We included 725 patients, identifying 29 with PCR-confirmed COVID-19 infection and 16 with COVID-19-like symptoms without PCR-testing. Of the 29 confirmed cases, 7 had severe disease, 8 required hospital admission (27.6%), 4 intensive care, and 1 died. COVID-19 accumulated incidence was higher in lupus patients. Health care workers and anti-SSA/Ro52 antibody positivity were risk factors for COVID-19 susceptibility, and hypocomplementemia for severity. SARS-CoV-2 IgG antibodies were detected in 8.33% of patients. Three fourths of confirmed COVID-19 cases developed antibodies. High prednisone doses were associated with lack of antibody response. Antibody titers declined over time (39%). Convalescent patients at week 12 after symptom onset displayed a CD8T cell reduction and predominant Th17 with a mild Th2 response, more pronounced in severe COVID-19 disease. Longitudinal immune response analysis showed a progressive sustained increase in CD8 T and B memory cells with a decrease of Th17 signaling. Lupus patients are at higher risk of COVID-19 infection and new susceptibility and severity risk factors were identified. Lupus patients were able to mount humoral and cellular responses despite immunosuppressive therapy.

摘要

在系统性红斑狼疮(SLE)中,潜在的免疫失调和免疫抑制可能会增加感染 COVID-19 的易感性,并损害体液和适应性免疫反应。我们旨在描述 COVID-19 感染,确定易感性和严重程度的危险因素,评估 SARS-CoV-2 IgG 抗体的存在情况,并分析细胞反应。我们建立了一个前瞻性狼疮患者队列,以估计与参考普通人群相比 COVID-19 的发病率。通过电话访谈和病历回顾收集数据。SARS-CoV-2 IgG 抗体作为常规监测的一部分进行横断面测量。在症状出现后 6、12 和 24 周评估 COVID-19 恢复期患者的抗体滴度和免疫谱的纵向变化。从免疫学研究中,从恢复期患者中提取 PBMC 并通过流式细胞术和基因表达分析进行分析。我们纳入了 725 名患者,其中 29 名患者的 PCR 检测结果为 COVID-19 感染确诊,16 名患者为 COVID-19 样症状但未进行 PCR 检测。在 29 例确诊病例中,有 7 例为重症,8 例需要住院治疗(27.6%),4 例需要重症监护,1 例死亡。狼疮患者 COVID-19 的累积发病率更高。医护人员和抗 SSA/Ro52 抗体阳性是 COVID-19 易感性的危险因素,低补体血症是严重程度的危险因素。8.33%的患者检测到 SARS-CoV-2 IgG 抗体。四分之三的确诊 COVID-19 病例产生了抗体。高剂量泼尼松与缺乏抗体反应有关。抗体滴度随时间下降(39%)。症状出现后 12 周的恢复期患者显示 CD8T 细胞减少,Th17 为主伴有轻度 Th2 反应,在严重 COVID-19 疾病中更为明显。纵向免疫反应分析显示,CD8 T 和 B 记忆细胞持续增加,Th17 信号减少。狼疮患者感染 COVID-19 的风险更高,并确定了新的易感性和严重程度的危险因素。尽管接受了免疫抑制治疗,但狼疮患者仍能产生体液和细胞反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9c8/9374766/e5d414fbcf87/41598_2022_17334_Fig1_HTML.jpg

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