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预测免疫功能低下患者中新冠病毒的持续脱落:一种基于概率的方法。

Predicting persistent SARS-CoV-2 shedding in immunocompromised patients: a probability-based approach.

作者信息

Chang Euijin, Kim Jun-Won, Jang Choi-Young, Kim Ji Yeun, Kang Sung-Woon, Bae Seongman, Jung Jiwon, Kim Min Jae, Chong Yong Pil, Lee Sang-Oh, Choi Sang-Ho, Yun Sung-Cheol, Kim Yang Soo, Yang Jeong-Sun, Kim Kyung-Chang, Lee Joo-Yeon, Kim Sung-Han

机构信息

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Center for Emerging Virus Research, National Institute of Infectious Diseases, Korea Disease Control and Prevention Agency, Cheongju, South Korea.

出版信息

Infect Dis (Lond). 2025 May;57(5):407-416. doi: 10.1080/23744235.2024.2446286. Epub 2025 Jan 3.

Abstract

BACKGROUND

Although recommended isolation periods for Coronavirus disease 2019 (COVID-19) have been shortened as the pandemic has subsided, prolonged Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) shedding remains common in immunocompromised patients. This study estimated the probability of viral clearance in these patients based on elapsed days and specific risk factors.

METHODS

We prospectively enrolled immunocompromised patients with a confirmed COVID-19 diagnosis from January 2022 to May 2023 during the Omicron variant era. We collected weekly respiratory specimens for viral load measurement and culture. We identified significant predictors of viral culture negative conversion through univariate and multivariate analyses and estimated viral clearance probabilities using a Cox time-varying proportional hazard model.

RESULTS

Among 70 patients with serial 319 respiratory specimens with positive SARS-CoV-2 genomic polymerase chain reaction results that underwent cell culture, ∼69% (48) had haematologic malignancies and 31% (22) underwent solid organ transplants. B-cell depleting agents and viral copy number significantly influenced viral culture negative conversion. The probability of culture-negative conversion for immunocompromised patients not treated with B-cell-depleting agents increased over time, with over 90% achieving negative conversion by Day 84. Patients treated with B-cell depleting agents showed lower conversion rates. By Day 84, <90% of patients with cycle threshold values 23-28 [4.85-6.35 log copies/mL] achieved culture-negative conversion. The results indicate more prolonged shedding than in patients without B-cell depletion.

CONCLUSION

Estimating SARS-CoV-2 clearance probabilities based on specific risk factors can guide individualised isolation decisions for immunocompromised patients, tailoring policies to each patient's delayed viral clearance risk.

摘要

背景

尽管随着疫情缓解,2019年冠状病毒病(COVID-19)的推荐隔离期已缩短,但在免疫功能低下的患者中,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)长时间脱落仍很常见。本研究根据病程天数和特定风险因素估计了这些患者病毒清除的概率。

方法

我们前瞻性纳入了2022年1月至2023年5月奥密克戎变异株流行期间确诊为COVID-19的免疫功能低下患者。我们每周收集呼吸道标本进行病毒载量测量和培养。我们通过单因素和多因素分析确定病毒培养阴性转化的显著预测因素,并使用Cox时变比例风险模型估计病毒清除概率。

结果

在70例连续319份SARS-CoV-2基因组聚合酶链反应结果呈阳性并接受细胞培养的呼吸道标本的患者中,约69%(48例)患有血液系统恶性肿瘤,31%(22例)接受了实体器官移植。B细胞耗竭剂和病毒拷贝数显著影响病毒培养阴性转化。未接受B细胞耗竭剂治疗的免疫功能低下患者培养阴性转化的概率随时间增加,超过90%的患者在第84天实现阴性转化。接受B细胞耗竭剂治疗的患者转化率较低。到第84天,循环阈值为23-28[4.85-6.35 log拷贝/mL]的患者中,<90%实现培养阴性转化。结果表明,与未进行B细胞耗竭的患者相比,病毒脱落时间更长。

结论

根据特定风险因素估计SARS-CoV-2清除概率可为免疫功能低下患者的个体化隔离决策提供指导,根据每位患者延迟病毒清除的风险制定相应政策。

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