SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
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DOI：
10.1016/s2666-5247(20)30172-5
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Ho A
中科院分区：
文献类型：
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作者：
Cevik M;Tate M;Lloyd O;Maraolo AE;Schafers J;Ho A
病毒载量动力学和病毒脱落持续时间是疾病传播的重要决定因素。我们的目的是表征严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 在各种体液中的病毒载量动态、病毒 RNA 脱落的持续时间和活病毒脱落，并比较 SARS-CoV-2、SARS-CoV 和中东呼吸综合征冠状病毒 (MERS-CoV) 的病毒动态。在这项系统评价和荟萃分析中，我们检索了 MEDLINE、Embase、Europe PubMed Central、medRxiv 和 bioRxiv 等数据库以及灰色文献，查找 2003 年 1 月 1 日至 2020 年 6 月 6 日之间发表的研究文章。我们纳入了病例系列（有 5 名或更多参与者）、队列研究和随机对照试验，报告了 SARS-CoV-2、SARS-CoV 或 MERS-CoV 感染，并报告了病毒载量动力学、病毒脱落的持续时间或活病毒。两位作者独立地从已发表的研究中提取数据，或联系作者索取数据，并使用乔安娜·布里格斯研究所批判性评估清单工具评估研究质量和偏倚风险。我们计算了每项研究的病毒脱落平均持续时间和 95% CI，并应用随机效应模型来估计汇总效应大小。我们使用带有无限制最大似然模型的加权元回归来评估潜在调节因素对汇总效应大小的影响。本研究已在 PROSPERO 注册，CRD42020181914。纳入了 79 项关于 SARS-CoV-2 的研究（5340 人）、8 项关于 SARS-CoV 的研究（1858 人）以及 11 项关于 MERS-CoV 的研究（799 人）。上呼吸道中 SARS-CoV-2 RNA 脱落的平均持续时间为 17·0 天（95% CI 15·5–18·6；43 项研究，3229 名个体），下呼吸道中为 14·6 天（9·3–20·0；7 项研究，260 名个体），粪便中为 17·2 天（14·4–20·1；13 项研究，586 名个体），以及血清样本中 16·6 天（3·6–29·7；两项研究，108 名个体）。上呼吸道最长排毒时间为83天，下呼吸道最长排毒时间为59天，粪便中最长排毒时间为126天，血清中最长排毒时间为60天。汇总平均 SARS-CoV-2 脱落持续时间与年龄呈正相关（斜率 0·304 [95% CI 0·115–0·493]；p=0·0016）。尽管从周期阈值推断出病毒载量持续较高，但在患病第 9 天之后，没有研究检测到活病毒。上呼吸道中的 SARS-CoV-2 病毒载量似乎在患病第一周达到峰值，而 SARS-CoV 的病毒载量在第 10-14 天达到峰值，MERS-CoV 的病毒载量在第 7-10 天达到峰值。尽管呼吸道和粪便样本中 SARS-CoV-2 RNA 的脱落时间可能会延长，但病毒的存活时间相对较短。上呼吸道的 SARS-CoV-2 滴度在患病第一周达到峰值。早期病例发现和隔离以及有关疾病谱和传染期的公众教育是有效遏制 SARS-CoV-2 的关键。没有任何。
Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics. In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914. 79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5–18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3–20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4–20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6–29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115–0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10–14 and that of MERS-CoV peaked at days 7–10. Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2. None.