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

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

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预测免疫功能低下患者持续的SARS-CoV-2脱落:一种基于概率的方法
背景:尽管随着大流行的消退,2019冠状病毒病(COVID-19)的推荐隔离期已经缩短,但在免疫功能低下的患者中,长时间的严重急性呼吸综合征-冠状病毒-2 (SARS-CoV-2)脱落仍然很常见。该研究根据经过的天数和特定的危险因素估计了这些患者病毒清除的可能性。方法:我们前瞻性地招募了2022年1月至2023年5月在欧米克隆变异时代确诊的COVID-19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定和培养。我们通过单变量和多变量分析确定了病毒培养阴性转化的重要预测因素,并使用Cox时变比例风险模型估计了病毒清除概率。结果:在70例接受细胞培养的319例SARS-CoV-2基因组聚合酶链反应结果阳性的呼吸道标本中,69%(48例)患有血液病恶性肿瘤,31%(22例)接受了实体器官移植。b细胞消耗剂和病毒拷贝数显著影响病毒培养阴性转化。未使用b细胞消耗药物治疗的免疫功能低下患者培养阴性转化的可能性随着时间的推移而增加,到第84天超过90%的患者实现阴性转化。接受b细胞消耗剂治疗的患者转化率较低。结论:基于特定风险因素估算SARS-CoV-2清除概率,可以指导免疫功能低下患者的个性化隔离决策,根据每位患者的延迟病毒清除风险量身定制政策。
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