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. Results: The 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 of the 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% CI 1.30-6.51, P=0.010), CLL progressive (OR=3.79, 95% CI 1.57-9.15, P=0.003) and CD20 antibody-based treatments 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, CLL progressive (OR=2.98, 95% CI 1.10-8.10, P=0.033) was an independent risk factor for severe/critical COVID-19 and administration of the BTK (Bruton tyrosine kinase) inhibitor monotherapy might exert a protective 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) had multiple 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 any reason). The peak value of the anti-SARS-CoV-2-IgG titres was observed between three and four months post symptom onset (median: 3.511 S/CO vs 1.047 S/CO, P<0.05). The levels of immunoglobulin A gradually decreased following infection with COVID-19, and its trough levels were attained between two to four weeks post infection (median: 0.30 g/L vs 0.74 g/L, P<0.05). According to this study the mortality of patients suffering from a combination of COVID-19 infection and CLL was 2.7% (9/328), and the main reason for their death was respiratory failure and heart failure. Conclusions: A low rate of COVID-19 vaccination and a high rate of severe/critical COVID-19 infection was observed in the CLL patients. CLL progressive was associated with severe/critical COVID-19. Anti-CD20-based treatments received within the past three months might be a risk factor for exacerbation of COVID-19 infection, whereas a monotherapy with BTK inhibitors exert a protective effect and improve outcome of COVID-19 infection.
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% CI 1.24～3.73，P＝0.006）、合并糖尿病（OR＝2.09，95% CI 1.05～4.20，P＝0.037）、慢性乙型肝炎（OR＝2.91，95% CI 1.30～6.51，P＝0.010）、CLL进展状态（OR＝3.79，95% CI 1.57～9.15，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% CI 1.35～5.77，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% CI 1.10～8.10，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% CI 0.16～0.90，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：3.511 S/CO对1.047 S/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：0.30 g/L对0.74 g/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。.
Keywords: Anti-CD20-based treatments; BTK inhibitors; COVID-19; Leukemia, lymphocytic, chronic, B-cell; Omicron; SARS-CoV-2.