Department of Infectious Disease, Shanghai Public Health Clinical Center, Shanghai 201508, China.
Department of Infectious Disease and Immunology, Shanghai Public Health Clinical Center, Shanghai 201508, China.
Chin Med J (Engl). 2020 May 5;133(9):1039-1043. doi: 10.1097/CM9.0000000000000774.
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.
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.
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 = 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).
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.
患者的传染性取决于其不同体液、分泌物和排泄物中病毒的存在情况。对于 2019 年新型冠状病毒病（COVID-19）患者，不同标本中病毒 RNA 的持续时间和清除情况仍不清楚。本研究分析了 COVID-19 患者不同样本中 2019 年新型冠状病毒（2019-nCoV）RNA 的清除时间及其影响因素，为改善患者恢复期的管理提供了进一步的证据。
回顾性收集 2020 年 1 月 20 日至 2 月 10 日收治的 COVID-19 恢复期患者的临床数据和实验室检测结果。收集并分析患者咽拭子、粪便、尿液和血清样本的逆转录聚合酶链反应（RT-PCR）结果。恢复期患者指的是体温正常、无呼吸道症状且连续 2 次（采样间隔至少 24 小时）咽拭子 RT-PCR 病毒 RNA 结果均为阴性的非发热患者。分析了 CD4+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。
在 292 例确诊病例中，66 例经治疗后康复并纳入本研究。共有 28 名（42.4%）女性和 38 名（57.6%）男性，中位年龄为 44.0（34.0-62.0）岁。住院治疗后，患者的炎症指标随着临床状况的改善而降低。恢复期患者咽拭子首次 RT-PCR 结果为阴性的中位时间为 9.5（6.0-11.0）天。到 2020 年 2 月 10 日，仍有 11 例恢复期患者（16.7%）粪便标本检测到病毒 RNA 阳性，其余 55 例患者的粪便标本在症状出现后中位时间 11.0（9.0-16.0）天内均检测不到 2019-nCoV。在这 55 例患者中，有 43 例患者粪便标本病毒 RNA 转为阴性的时间长于咽拭子，中位延迟时间为 2.0（1.0-4.0）天。58 例尿液样本中仅有 4 例（6.9%）病毒核酸检测结果为阳性，在咽拭子转为阴性后，仍有 3 例患者的尿液标本中存在病毒 RNA。使用多元线性回归模型（F = 2.669，P = 0.044，调整 R = 0.122）分析表明，CD4+T 淋巴细胞计数可能有助于预测患者粪便中病毒 RNA 检测的持续时间（t = -2.699，P = 0.010）。糖皮质激素治疗组的咽拭子和粪便样本中病毒 RNA 检测持续时间长于非糖皮质激素治疗组（分别为 15 天和 8.0 天；t = 2.550，P = 0.013），糖皮质激素治疗组的粪便样本中病毒 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 检测结果阳性患者与阴性患者的炎症指标无统计学差异（P > 0.05）。
简而言之，由于患者粪便中病毒 RNA 的清除时间比咽拭子中延迟，因此在恢复期识别粪便中的病毒 RNA 很重要。由于糖皮质激素治疗组病毒 RNA 清除延迟，不建议在 COVID-19 的治疗中使用糖皮质激素，特别是对于轻症患者。RNA 检测持续时间可能与宿主细胞免疫有关。
