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Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients.
2019 年新型冠状病毒疾病康复患者病毒RNA的持久性和清除率。
- 影响因子:1.16
- DOI:10.1097/CM9.0000000000000774
- 作者列表:"Ling Y","Xu SB","Lin YX","Tian D","Zhu ZQ","Dai FH","Wu F","Song ZG","Huang W","Chen J","Hu BJ","Wang S","Mao EQ","Zhu L","Zhang WH","Lu HZ
- 发表时间:2020-05-05
Abstract
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 = 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.
摘要
背景: 患者的传染性取决于病毒在不同体液、分泌物和排泄物中的存在。2019 新型冠状病毒患者不同标本中病毒RNA的持久性和清除率 (新型冠状病毒肺炎) 仍不清楚。本研究分析了 2019新型冠状病毒(2019-nCoV) 患者不同样本新型冠状病毒肺炎RNA清除时间及影响因素,为提高患者恢复期管理提供进一步证据。 方法: 回顾性收集 2020 年 1 月 20 日至 20 20 0 年 2 月 10 日收治的新型冠状病毒肺炎恢复期患者的临床资料及实验室检查结果。收集患者口咽拭子、粪便、尿液和血清样本的逆转录聚合酶链反应 (RT-PCR) 结果并进行分析。恢复期患者是指口咽拭子病毒RNA连续两次 (最小 24 h采样间隔) RT-PCR结果阴性的无呼吸道症状的恢复期非发热患者。分析分化簇 4 (CD4)+ T淋巴细胞、炎症指标、糖皮质激素治疗对病毒核酸清除的影响。 结果: 在 292 例确诊病例中,66 例患者经治疗后痊愈,纳入本研究。总共分析了 28 (42.4%) 名女性和 38 名男性 (57.6%),中位年龄为 44.0 (34.0-62.0) 岁。住院治疗后,患者炎性指标下降,临床病情好转。恢复期患者口咽拭子从出现症状到首次RT-PCR结果阴性的中位时间为 9.5 (6.0-11.0) 天。截止 2020 年 2 月 10 日,11 名恢复期患者 (16.7%) 从粪便标本中检测病毒RNA仍然呈阳性,其他 55 例患者的粪便标本在症状出现后中位持续时间为 2019 (11.0-9.0) 天,16.0-nCoV呈阴性。在这 55 例患者中,43 例至粪便标本病毒RNA阴性的持续时间长于咽拭子,中位延迟 2.0 (1.0-4.0) 天。结果 58 例中仅 4 例 (6.9%) 尿液标本病毒核酸阳性; 3 例患者咽拭子阴性后尿液标本仍存在病毒RNA。使用多元线性回归模型 (f = 2.669,p = 0.044,校正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)。糖皮质激素治疗组从口咽拭子和粪便样本中检测病毒RNA的持续时间长于非糖皮质激素治疗组 (15 天vs.分别为 8.0 天; T = 2.550,p = 0.013)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 (20 d vs.分别为 11 天; T = 4.631,p <0.001)。粪便病毒RNA检测结果阳性者与阴性者炎症指标差异无统计学意义 (p> 0.05)。 结论: 总之,与口咽拭子相比,患者粪便中病毒RNA的清除延迟,因此在恢复期鉴定粪便中的病毒RNA非常重要。由于糖皮质激素治疗组的病毒RNA清除延迟,糖皮质激素不推荐用于新型冠状病毒肺炎的治疗,特别是对于轻症。RNA检测的持续时间可能与宿主细胞免疫有关。
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METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.
呼吸道感染分为上呼吸道感染与下呼吸道感染。上呼吸道感染是指自鼻腔至喉部之间的急性炎症的总称,是最常见的感染性疾病。下呼吸道感染是最常见的感染性疾患,治疗时必须明确引起感染的病原体以选择有效的抗生素。