Asymptomatic transmission in the COVID-19 pandemic: a systematic review and Meta-analysis
LI Zi-shuai and LIN Jian-sheng contributed equally to this article
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摘要:
目的 确定SARS-CoV-2无症状感染者与COVID-19患者流行病学特征差异。 方法 提取PubMed、Web of Science、中国知网、维普网、万方数据知识服务平台内SARS-CoV-2无症状传播文献相关数据，截止日期为2020年8月1日。根据预先制定的纳入排除标准筛选和提取流行病学信息。对无症状传播者的年龄、性别、病毒RNA脱落时间及病毒载量等情况进行汇总和分析。 结果 共38篇文献符合标准, 其中17篇文献为无症状感染病毒RNA脱落时间相关病例报告。与有症状感染者相比，无症状感染者更加年轻[加权均数差(weighted mean difference, WMD), WMD=-5.27, 95% CI: -9.78~-0.76, P＜0.001]、病毒RNA脱落时间(中位数：11 d)较有症状感染者缩短(中位数：16 d)(P＜0.001)、上呼吸道拭子核酸载量较低(WMD=2.36, 95% CI: 0.65~4.07, P=0.007)，二者性别组成无统计学差异。 结论 与COVID-19患者相比，SARS-CoV-2无症状感染者较年轻，病毒载量较低，病毒RNA脱落时间较短。 Abstract:Objective To determine the differences in the epidemiological characteristics of asymptomatic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) patients. Methods The relevant data of asymptomatic SARS-CoV-2 transmission literature in PubMed, Web of Science, CNKI, VIP medicine and Wanfang medical database were extracted as of August 1, 2020. Epidemiological information was screened and extracted according to pre-established inclusion and exclusion criteria. Age, gender, virus shedding duration and virual load of asymptomatic carriers were summarized and analyzed. Results A total of 38 articles met the criteria, 17 of which were asymptomatic case reports related to the virus shedding duration. Compared with symptomatic infected persons, asymptomatic individuals were younger [Weighted Mean Difference (WMD), WMD=-5.27, 95% CI: -9.78--0.76, P < 0.001] and the viral load was lower (WMD=2.36, 95% CI: 0.65-4.07, P=0.007). The virus shedding duration of asymptomatic individuals (median=11 days) was shorter than symptomatic patients (median=16 days). Conclusion Asymptomatic individuals with SARS-CoV-2 were younger, had a lower viral load and a shorter virus shedding duration than COVID-19 patients. -
Key words:
- SARS-CoV-2 /
- COVID-19 /
- Asymptomatic transmission /
- Virus shedding duration /
- Cycle threshold values
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图 2 无症状感染者与有症状感染者年龄特征的森林图与漏斗图
Figure 2. The forest and funnel plots of age characteristics about asymptomatic and symptomatic infected people
图 3 无症状感染者与有症状感染者性别分布的森林图和漏斗图
Figure 3. The forest and funnel plots of gender distribution about asymptomatic and symptomatic infected people
图 4 无症状感染者病毒载量的森林图和漏斗图
Figure 4. The forest and funnel plots of viral load in asymptomatic infected people
表 1 文献质量评价表
Table 1. Quality evaluation table about the literature
作者 收集时间 地区 样本量 评分 质量 Chau NVV, et al. [7] 2020.03.10―2020.04.04 越南胡志明市隔离中心 484 6 中 Han H, et al. [8] 中国武汉大学人民医院 26 9 高 Kong W, et al. [9] 2020.01.25―2020.02.20 中国四川省 511 8 高 Li Y, et al. [10] 2020.02.22―2020.03.08 中国武汉一家临时木屋医院 252 8 高 Long QX, et al. [6] 2020.01.21―2020.04.10 中国重庆市万州区 74 9 高 Ma Y, et al. [11] 2020.01.23―2020.03.10 中国山东大学济南传染病医院 43 5 中 Mei X, et al. [12] 2020.01.20―2020.03.31 中国上海市某定点医院 30 9 高 Samrah SM, et al. [13] 2020.03.15―2020.04.02 约旦北部 81 7 中 Schwierzeck V, et al. [14] 德国明斯特大学医院 12 10 高 Sohn Y, et al. [15] 2020.03.15―2020.04.10 韩国首尔 48 7 中 Tabata S, et al. [16] 2020.02.11―2020.02.25 日本自卫队中心医院 47 8 高 Wellinghausen N, et al. [17] 2020.03.24―2020.05.06 德国拉文斯堡 137 9 高 Yang R, et al. [18] 2019.12.24―2020.02.24 中国湖北省武汉市 78 8 高 Yu C, et al. [19] 2020.01.10―2020.03.15 中国湖北省武汉三家医院 1 568 7 中 Zhou R, et al. [20] 2020.01.23―2020.03.03 中国广州市第八人民医院 37 9 高 董玉颖, 等. [21] 2020.01―2020.02 中国江苏省扬州市 208 8 高 胡世雄, 等. [22] 2020.01.01―2020.02.08 中国湖南省 31 7 中 林君芬, 等. [23] 2020.01.21―2020.02.20 中国浙江省 53 5 中 刘碧瑶, 等. [24] 2020.03.01―2020.04.07 中国浙江省 1 284 5 中 王婉薇, 等. [25] 2020.01.23―2020.02.10 中国四川省内江市 5 5 中 叶莹, 等. [26] 2020.01―2020.03 中国河南省 91 6 中 
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表 2 无症状感染者与有症状感染者年龄特征分析
Table 2. Age characteristic analysis about asymptomatic and symptomatic infected people
作者 例数(例) 无症状(x±s) 有症状(x±s) WMD(95% CI)值 Chau NVV, et al. [7] 30 31.06±11.96a 32.59±12.25a -1.53(-10.26~7.20) Kong W, et al. [9] 511 37.70±19.00 44.00±15.40 -6.30(-10.31~-2.29) Samrah SM, et al. [13] 81 39.22±17.81 40.57±15.67 -1.35(-8.72~6.02) Tabata S, et al. [16] 43 67.15±13.95a 65.78±15.48a 1.37(-9.34~12.08) Yang R, et al. [18] 78 35.93±14.72a 50.69±22.21a -14.75(-22.96~-6.55) 董玉颖, 等. [21] 37 49.65±13.08 38.64±20.83 11.01(0.08~21.94) 胡世雄, 等. [22] 888 37.14±20.34 43.96±13.09 -6.82(-13.52~ -0.12) 林君芬, 等. [23] 1 284 38.15±30.91a 47.08±15.96a -8.92(-14.83~-3.02) 刘碧瑶, 等. [24] 91 32.05±13.54a 31.85±21.02a 0.20(-7.00~7.39) 叶莹, 等. [26] 208 32.88±29.76a 52.01±14.83a -19.13(-26.01~-12.26) 合计 3 251 -5.27(-9.78~ -0.76) 注：a：数据是经过转化得来[27-28]。
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表 3 无症状感染者与有症状感染者性别特征分析[n(%)]
Table 3. Age characteristic analysis about asymptomatic and symptomatic infected people [n(%)]
作者 男性无症状 男性有症状 OR(95% CI)值 Chau NVV, et al. [7] 7(53.85) 8(47.06) 1.31(0.31~5.58) Kong W, et al. [9] 55(55.00) 226(54.99) 1.00(0.64~1.55) Li Y, et al. [10] 35(47.30) 90(50.56) 0.88(0.51~1.51) Ma Y, et al. [11] 6(54.55) 14(38.89) 1.89(0.48~7.37) Mei X, et al. [12] 15(48.39) 245(54.08) 0.80(0.38~1.65) Samrah SM, et al. [13] 26(70.27) 11(25.00) 7.09(2.66~18.91) Tabata S, et al. [16] 15(45.45) 4(40.00) 1.25(0.30~5.27) Yang R, et al. [18] 11(33.33) 31(68.89) 0.23(0.09~0.59) Yu C, et al. [19] 32(40.51) 617(41.44) 0.96(0.61~1.53) Zhou R, et al. [20] 4(44.44) 6(27.27) 2.13(0.42~10.73) 董玉颖, 等. [21] 7(50.00) 10(43.48) 1.30(0.34~4.93) 胡世雄, 等. [22] 19(52.78) 379(44.48) 1.39(0.72~2.72) 林君芬, 等. [23] 49(45.37) 598(50.85) 0.80(0.54~1.19) 刘碧瑶, 等. [24] 25(58.14) 23(47.92) 1.51(0.66~3.46) 叶莹, 等. [26] 41(48.81) 68(54.84) 0.79(0.45~1.37) 合计 347(49.22) 2 330(49.28) 1.06(0.80~1.42)
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表 4 无症状感染者病毒RNA脱落时间
Table 4. The viral RNA shedding duration in asymptomatic infected persons
作者 地区或发布机构 例数(例) 病毒RNA脱落时间(中位数) 无症状 有症状 无症状 有症状 Li W, et al. [29] 中国重庆大学中心医院 3 15 13.0 14.0 Dong X, et al. [30] 湖北省武汉三家医院 1 8 2.0 19.0 Huang R, et al. [31] 中国江苏省宿迁市 1 1 14.0 16.0 Luo Y, et al. [32] 中国武汉大学中南医院 5 1 10.0 8.0 Tong ZD, et al. [33] 中国浙江省舟山市 2 2 5.5 9.5 Yang, MC, et al. [34] 中国台湾 3 2 7.0 36.0 Hu Z, et al. [35] 江苏省南京市第二人民医院 11 4 6.0 12.0 Jiang XL, et al. [36] 中国山东省 3 5 14.0 14.0 Zhang H, et al. [37] 江苏省盐城第三人民医院 4 9 15.5 17.0 白红春, 等. [38] 中国重庆市铜梁区 5 0 20.0 晁湘琴, 等. [39] 中国苏州市姑苏区 1 0 12.0 王蔚茹, 等. [40] 中国山东省济南市 1 4 25.0 24.0 魏伟, 等. [41] 中国四川省德阳市人民医院 1 0 14.0 杨丽丽, 等. [42] 温州医科大学附属第二医院 1 0 18.0 姚行艳, 等. [43] 中国内蒙古自治区包头市 1 6 24.0 26.0 郑志林, 等. [44] 云南省曲靖市第一人民医院 1 0 35.0 周仁彬, 等. [45] 江西省宜春市人民医院 1 0 4.0 合计 45 57 11.0 16.0
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表 5 无症状感染者病毒载量
Table 5. Viral load in asymptomatic infected people
作者 例数(例) 样本来源 检测基因片段 无症状(x±s) 有症状(x±s) WMD(95% CI) Han H, et al. [8] 26 ORF1ab 37.74±2.96 36.47±3.79 1.27(-1.79~4.33) Long QX, et al. [6] 74 首次阳性拭子 ORF1ab 33.19±3.78a 32.41±3.70a 0.78(-0.92~2.49) Schwierzeck V, et al. [14] 12 确诊4 d后 E 29.81±6.09a 21.13±2.91a 8.68(3.29~14.08) Sohn Y, et al. [15] 48 确诊2周内 E 30.55±2.96 27.60±0.47 2.95(1.96~3.94) Wellinghausen N, et al. [17] 101 E 34.44±4.81 28.96±5.70 5.48(2.99~7.97) Zhou R, et al. [20] 19 入院后 38.61±2.01a 34.57±3.95a 4.04(1.32~6.76) 王婉薇, 等. [25] 5 确诊后3 d内 24.00±4.32 27.50±0.50 -3.50(-8.44~1.44) 董玉颖, 等. [21] 37 暴露后8~9 d ORF1ab 31.01±3.68 31.56±4.98 -0.55(-3.56~2.46) 合计 322 2.36(0.65~4.07) 注：a：数据是经过转化得来[27-28]; ORF1ab: open reading frame 1ab，开放阅读框1ab; E: envelope protein，包膜蛋白。
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