慢性淋巴细胞白血病患者COVID-19的单中心报告  

Single-center study of COVID-19 in patients with chronic lymphocytic leukemia

作　　者：路萧 高玲 钱思褀 戴罗梦佳 周子元 邱彤璐 夏奕[1] 缪祎 秦姝超 范磊[1] 徐卫[1] 李建勇[1] 朱华渊[1,2] Lu Xiao;Gao Ling;Qian Siqi;Dai Luomengjid;Zhou Ziyuan;Qiu Tonglu;Xia Yi;Miao Yi;Qin Shuchao;Fan Lei;Xu Wei;Li Jianyong;Zhu Huayuan(Department of Hematology,The First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China;Department of Hematology,The Affliate Suqian First People's Hospital of Nanjing Medical University,Suqian Branch of Jiangsu Provincial People's Hospital,Suqian 223999,China)

机构地区：[1]南京医科大学第一附属医院,江苏省人民医院血液科,南京210029 [2]南京医科大学附属宿迁第一人民医院,江苏省人民医院宿迁分院血液科,宿迁223999

出　　处：《中华血液学杂志》2024年第10期923-930,共8页Chinese Journal of Hematology

基　　金：国家自然科学基金(82170166、82100207);江苏省科教能力提升工程(ZDXK202209)。

摘　　要：目的研究旨在了解中国慢性淋巴细胞白血病(CLL)患者、新型冠状病毒感染(COVID-19)的临床特征、感染风险、转归及疫苗接种情况。方法回顾性分析2022年11月至2023年2月在南京医科大学第一附属医院血液科就诊的328例首次确诊COVID-19的CLL患者的临床资料,应用二元Logistic回归模型进行重/危重症COVID-19的单因素、多因素分析。结果患者中位年龄为60(24~87)岁,23.5%(77/328)的患者为重/危重症COVID-19。在单因素分析中,年龄67岁(OR=2.15,95%CI1.24~3.73,P=0.006)、合并糖尿病(OR=2.09,95%CI1.05~4.20,P=0.037)、慢性乙型肝炎(OR=2.91,95%CI1.30~6.51,P=0.010)、CLL进展状态(OR=3.79,95%CI1.57~9.15,P=0.003)和确诊COVID-19之前3个月内使用CD20单抗治疗(OR=2.79,95%CI1.35~5.77,P=0.006)是重/危重症COVID-19的危险因素;在多因素分析中,CLL进展状态(OR=2.98,95%CI1.10~8.10,P=0.033)是重/危重症COVID-19的独立危险因素,另外,接受单药布鲁顿酪氨酸激酶抑制剂(BTKi)可能使重/危重症COVID-19风险减低(OR=0.38,95%CI0.16~0.90,P=0.028)。对其中242例患者进一步随访至2023年10月,9.1%(22/242)患者在后续多次感染(≥3次),2.1%(5/242)患者持续感染。患者体内新型冠状病毒抗体IgG滴度在感染后3~4个月达峰值(中位值:3.511S/CO对1.047S/CO,P<0.05);免疫球蛋白IgA在COVID-19后逐渐降低,且在2~4周至低谷(中位值:0.30g/L对0.74g/L,P<0.05)。整体队列中COVID-19合并CLL病死率为2.7%(9/328),主要死亡原因为呼吸衰竭和心源性猝死。结论CLL患者新型冠状病毒疫苗接种率较低,重/危重症COVID-19比例高。CLL疾病进展是CLL患者发生重/危重症COVID-19的独立危险因素;3个月内CD20单抗治疗是加重COVID-19的危险因素,而持续的BTKi治疗可能减轻重/危重症COVID-19的风险。Objective To investigate the vaccination status,characteristics and prognosis of patients suffering from a combination of COVID-19 and chronic lymphocytic anemia(CLL)in China.Methods Clinical data of 328 patients with chronic lymphocytic leukemia(CLL)who were first diagnosed with COVID-19 and treated in the Department of Hematology of Jiangsu Provincial People's Hospital between November 2022 and February 2023 were retrospectively analyzed.Univariate and multivariate analysis of data of patients with severe/critical COVID-19 were conducted by applying the binary logistic regression model.ResultssThe median age of the CLL patients was 60(24-87)years.23.5% (77/328) of these patients suffered from severe/critical COVID-19 infection. Univariate analysis ofthe data demonstrated that a combination of factors including age >67 years (OR=2.15, 95% CI 1.24-3.73, P=0.006), diabetes (OR=2.09, 95% CI 1.05-4.20, P=0.037), chronic hepatitis B (OR=2.91, 95% CI1.30-6.51, P=0.010), CLL progressive (OR=3.79, 95% CI 1.57-9.15, P=0.003) and CD20 antibodybasedtreatments within three months prior to the COVID-19 infection (OR=2.79, 95% CI 1.35-5.77, P=0.006) were the risk factors for severe/critical COVID-19. According to the multivariate analysis, CLLprogressive (OR=2.98, 95% CI 1.10-8.10, P=0.033) was an independent risk factor for severe/criticalCOVID-19 and administration of the BTK (Bruton tyrosine kinase) inhibitor monotherapy might exert aprotective effect and influence a positive outcome of the COVID-19 infection (OR=0.38, 95% CI 0.16-0.90, P=0.028). Among the 242 patients who were followed up until October 2023, 9.1% (22/242) hadmultiple subsequent COVID-19 infections (≥3), and 2.1% (5/242) had persistent COVID-19 infections(patients with persistent positive test for the SARS-CoV-2 antigen testing until missing follow-up for anyreason). The peak value of the anti-SARS-CoV-2-IgG titres was observed between three and four monthspost symptom onset (median: 3.511 S/CO vs 1.047 S/CO, P<0.05). The levels of immunoglobulin Agradua

关 键 词：白血病 淋巴细胞 慢性 B细胞 新型冠状病毒感染 新型冠状病毒 奥密克戎 布鲁顿酪氨酸酶抑制剂 CD20单抗 

分 类 号：R733.72[医药卫生—肿瘤] R511[医药卫生—临床医学]