Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients
Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients
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DOI：
10.1097/cm9.0000000000000774
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发表时间：
2020-05-05
影响因子：
6.1
通讯作者：
Lu, Hong-Zhou
中科院分区：
文献类型：
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作者：
Ling, Yun;Xu, Shui-Bao;Lu, Hong-Zhou
背景：病人的传染性取决于不同体液、分泌物和排泄物中病毒的存在。来自2019年新型冠状病毒病（COVID-19）患者不同标本的病毒RNA的持久性和清除仍不清楚。本研究分析了COVID-19患者不同样本中2019新型冠状病毒（2019-nCoV）RNA的清除时间和影响因素，为改善恢复期患者的管理提供了进一步的证据。研究方法：回顾性收集2020年1月20日至2020年2月10日期间收治的COVID-19恢复期患者的临床资料和实验室检查结果。收集并分析患者口咽拭子、粪便、尿液和血清样本的逆转录聚合酶链反应（RT-PCR）结果。恢复期患者是指无呼吸道症状的恢复期非发热患者，其口咽拭子病毒RNA连续两次（至少24 h采样间隔）RT-PCR结果均为阴性。分析了分化簇4（CD 4）+ T淋巴细胞、炎症指标和糖皮质激素治疗对病毒核酸清除的影响。结果：292例确诊病例中，66例经治疗后痊愈，纳入本研究。共分析了28例（42.4%）女性和38例（57.6%）男性，中位年龄为44.0（34.0-62.0）岁。住院治疗后，患者的炎症指标下降，临床状况改善。恢复期患者从症状发作到首次口咽拭子RT-PCR结果阴性的中位时间为9.5（6.0-11.0）天。截至2020年2月10日，11名康复期患者（16.7%）在症状发作后的中位持续时间为11.0（9.0-16.0）天后，粪便标本中的病毒RNA检测结果仍为阳性，其他55名患者的粪便标本对2019-nCoV呈阴性。在这55名患者中，43名患者的粪便标本病毒RNA阴性持续时间长于咽拭子，中位延迟时间为2.0（1.0-4.0）天。结果58例患者中仅4例（6.9%）尿液病毒核酸阳性，3例咽拭子阴性后仍有病毒RNA存在。采用多元线性回归模型（F = 2.669，P = 0.044，校正R-2 = 0.122）分析表明，CD 4 + T淋巴细胞计数可帮助预测患者粪便中病毒RNA检测的持续时间（t =-2.699，P = 0.010）。糖皮质激素治疗组患者口咽拭子和粪便标本中病毒RNA检测持续时间均长于非糖皮质激素治疗组（分别为15天和8.0天; t = 2.550，P = 0.013），且糖皮质激素治疗组粪便标本中病毒RNA检测持续时间长于非糖皮质激素治疗组（分别为20天和11天; t = 4.631，P < 0.001）。粪便病毒RNA检测结果阳性与阴性患者的炎症指标差异无统计学意义（P > 0.05）。结论：简而言之，由于患者粪便中的病毒RNA清除较口咽拭子中的病毒RNA清除延迟，因此在恢复期对粪便中的病毒RNA进行鉴定非常重要，由于糖皮质激素治疗组的病毒RNA清除延迟，因此不建议在COVID-19治疗中使用糖皮质激素，尤其是对于轻症患者。RNA检测的持续时间可能与宿主细胞免疫有关。
Background: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R-2 = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). Conclusions: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence.Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.