Garneau William M, Wang Kunbo, Liang Tao, Xu Yanxun, Gladstone Douglas E, Avery Robin K, D'Alessio Franco R, Robinson Matthew L, Sahetya Sarina K, Garibaldi Brian T, Gebo Kelly A, Dioverti M Veronica
Division of Hospital Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe St, Carnegie 2nd Floor, Suite 249, Room 256, Baltimore, MD, 21287, USA.
Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA.
Sci Rep. 2025 Mar 20;15(1):9647. doi: 10.1038/s41598-025-94024-y.
B-cell depletion therapy is employed in a variety of clinical contexts from auto-immune diseases to malignancy. Prior research on patients with prior B-cell depletion treatment has suggested a mortality risk in patients hospitalized with COVID-19 however previous case-control studies have differed in their methods of patient comparison. Patients previously treated with B-cell-depletion hospitalized with COVID-19 were compared to matched controls in the Johns Hopkins Health System between March 1, 2020 and November 30, 2021. The primary outcome was 30-day all-cause mortality. Secondary outcomes included time to severe illness or death and time to clinical improvement. To eliminate bias due to imbalanced covariates, each patient who had previously received B-cell depletion therapy was matched with patients who had not received therapy based on age, sex, race, WHO severity score, admission date, COVID-19 specific treatment, and vaccination status. Propensity scores were calculated from a multivariable logistic regression model and performed on the matched sets, using B-cell depletion as the outcome, where the propensity score was the probability of receiving B-cell depletion therapy. The propensity score included matched covariates as well as smoking status, medical comorbidities, and vaccination status. Cox proportional-hazards regression models were applied on the matched sets to perform time to death, time to severe illness or death, and time to clinical improvement analyses. 50 patients were identified who had received B-cell depletion therapy and were compared to 186 matched controls. Patients treated with B-cell depletion experienced 30-day mortality of 6.0% compared to 3.8% in controls, adjusted hazard ratio (aHR) 1.45 (95% CI 0.30 to 6.95). B-cell-depleted patients experienced a longer time to clinical improvement, aHR 0.65 (95% CI 0.45-0.94). In this cohort, patients treated with B-cell depletion experienced a higher mortality rate compared to matched controls however this was not statistically significant. This group also experienced a prolonged time to clinical improvement based on WHO severity score.
B细胞清除疗法被应用于从自身免疫性疾病到恶性肿瘤等多种临床情况。先前对接受过B细胞清除治疗的患者的研究表明,COVID-19住院患者存在死亡风险,然而先前的病例对照研究在患者比较方法上存在差异。在2020年3月1日至2021年11月30日期间,将约翰霍普金斯医疗系统中因COVID-19住院且先前接受过B细胞清除治疗的患者与匹配的对照组进行比较。主要结局是30天全因死亡率。次要结局包括出现重症或死亡的时间以及临床改善的时间。为消除因协变量不平衡导致的偏差,根据年龄、性别、种族、世界卫生组织严重程度评分、入院日期、COVID-19特异性治疗和疫苗接种状况,将每位先前接受过B细胞清除治疗的患者与未接受治疗的患者进行匹配。通过多变量逻辑回归模型计算倾向得分,并在匹配组中进行分析,以B细胞清除作为结局,其中倾向得分是接受B细胞清除疗法的概率。倾向得分包括匹配的协变量以及吸烟状况、合并症和疫苗接种状况。对匹配组应用Cox比例风险回归模型,以进行死亡时间、出现重症或死亡的时间以及临床改善时间的分析。确定了50例接受过B细胞清除治疗的患者,并与186例匹配的对照组进行比较。接受B细胞清除治疗的患者30天死亡率为6.0%,而对照组为3.8%,调整后风险比(aHR)为1.45(95%CI为0.30至6.95)。B细胞清除的患者临床改善时间更长,aHR为0.65(95%CI为0.45至0.94)。在该队列中,接受B细胞清除治疗的患者与匹配的对照组相比死亡率更高,但这在统计学上并不显著。根据世界卫生组织严重程度评分,该组患者临床改善时间也更长。