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中国香港和从中国湖北省撤离居民的 SARS-CoV-2 血清阳性率:一项多队列研究。

Seroprevalence of SARS-CoV-2 in Hong Kong and in residents evacuated from Hubei province, China: a multicohort study.

机构信息

State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, Pokfulam, The University of Hong Kong, Hong Kong Special Administrative Region, China.

出版信息

Lancet Microbe. 2020 Jul;1(3):e111-e118. doi: 10.1016/S2666-5247(20)30053-7. Epub 2020 Jun 3.


DOI:10.1016/S2666-5247(20)30053-7
PMID:33230504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7673299/
Abstract

BACKGROUND: The role of subclinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in perpetuating the COVID-19 pandemic is unknown because population seroprevalence data are absent. We aimed to establish the sensitivity and specificity of our enzyme immunoassay and microneutralisation assay, and the seroprevalence of SARS-CoV-2 in Hong Kong before and after the pandemic, as well as in Hong Kong residents evacuated from Hubei province, China. METHODS: We did a multicohort study in a hospital and university in Hong Kong. We evaluated the sensitivity of our enzyme immunoassay and microneutralisation assay with RT-PCR data from patients positive for SARS-CoV-2 and the specificity of our enzyme immunoassay and microneutralisation assay with archived serum samples collected before 2019. We compared the seropositivity of the general population of Hong Kong before and after the pandemic had begun, and determined the seropositivity of Hong Kong residents evacuated from Hubei province, China, in March, 2020. FINDINGS: Between Feb 26 and March 18, 2020, we assessed RT-PCR samples from 45 patients who had recovered from COVID-19 to establish the sensitivity of our enzyme immunoassay and microneutralisation assay. To establish the specificity of these assays, we retrieved archived serum. The sensitivity was 91·1% (41 of 45 [95% CI 78·8-97·5]) for the microneutralisation assay, 57·8% (26 of 45 [42·2-72·3]) for anti-nucleoprotein IgG, 66·7% (30 of 45 [51·1-80·0]) for anti-spike protein receptor binding domain (RBD) IgG, and 73·3% (33 of 45 [58·1-85·4]) for enzyme immunoassay (either positive for anti-nucleoprotein or anti-RBD IgG). The specificity was 100% (152 of 152 [95% CI 97·6-100·0]) for both the enzyme immunoassay and microneutralisation assay. Among the Hong Kong general population, 53 (2·7%) of 1938 were enzyme immunoassay positive, but of those who were positive, all 53 were microneutralisation negative, and no significant increase was seen in the seroprevalence between April 12, 2018, and Feb 13, 2020. Among asymptomatic Hubei returnees, 17 (4%) of 452 were seropositive with the enzyme immunoassay or the microneutralisation assay, with 15 (88%) of 17 seropositive with the microneutralisation assay, and two familial clusters were identified. INTERPRETATION: Our serological data suggest that SARS-CoV-2 is a new emerging virus. The seropositivity rate in Hubei returnees indicates that RT-PCR-confirmed patients only represent a small proportion of the total number of cases. The low seroprevalence suggests that most of the Hong Kong and Hubei population remain susceptible to COVID-19. Future waves of the outbreak are inevitable without a vaccine or antiviral prophylaxis. The role of age-related cross reactive non-neutralising antibodies in the pathogenesis of COVID-19 warrants further investigation. FUNDING: Richard and Carol Yu, May Tam Mak Mei Yin, Shaw Foundation (Hong Kong), Michael Tong, Marina Lee, and the Government Consultancy Service (see acknowledgments for full list).

摘要

背景:由于缺乏人群血清流行率数据,亚临床严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染在持续 COVID-19 大流行中的作用尚不清楚。我们旨在确定我们的酶联免疫吸附试验和微量中和试验的灵敏度和特异性,以及 SARS-CoV-2 在大流行前和大流行后在香港以及从中国湖北省撤离的香港居民中的血清流行率。

方法:我们在香港的一家医院和一所大学进行了一项多队列研究。我们使用来自 SARS-CoV-2 阳性患者的 RT-PCR 数据评估了我们的酶联免疫吸附试验和微量中和试验的灵敏度,并使用 2019 年前收集的存档血清样本评估了我们的酶联免疫吸附试验和微量中和试验的特异性。我们比较了大流行开始前后香港普通人群的血清阳性率,并确定了 2020 年 3 月从中国湖北省撤离的香港居民的血清阳性率。

结果:在 2020 年 2 月 26 日至 3 月 18 日期间,我们评估了 45 名从 COVID-19 中康复的患者的 RT-PCR 样本,以确定我们的酶联免疫吸附试验和微量中和试验的灵敏度。为了确定这些检测方法的特异性,我们检索了存档的血清。微量中和试验的灵敏度为 91.1%(41/45[95%CI78.8-97.5]),抗核蛋白 IgG 的灵敏度为 57.8%(26/45[42.2-72.3]),抗刺突蛋白受体结合域(RBD)IgG 的灵敏度为 66.7%(30/45[51.1-80.0]),酶联免疫吸附试验的灵敏度为 73.3%(33/45[58.1-85.4])(抗核蛋白或抗 RBD IgG 阳性)。酶联免疫吸附试验和微量中和试验的特异性均为 100%(152/152[95%CI97.6-100.0])。在香港普通人群中,1938 人中 53 人(2.7%)酶联免疫吸附试验阳性,但其中 53 人均为微量中和试验阴性,并且在 2018 年 4 月 12 日至 2020 年 2 月 13 日之间,血清流行率未显著增加。在无症状的湖北返乡人员中,有 17 人(4%)经酶联免疫吸附试验或微量中和试验呈阳性,其中 15 人(88%)经微量中和试验呈阳性,并发现了两个家族聚集性病例。

结论:我们的血清学数据表明,SARS-CoV-2 是一种新出现的病毒。湖北返乡人员的阳性率表明,经 RT-PCR 确诊的患者仅代表了总病例数的一小部分。低血清流行率表明,香港和湖北的大部分人口仍然容易感染 COVID-19。如果没有疫苗或抗病毒预防措施,未来不可避免会出现疫情爆发。年龄相关的交叉反应性非中和抗体在 COVID-19 发病机制中的作用值得进一步研究。

资助:Richard 和 Carol Yu、May Tam Mak Mei Yin、Shaw Foundation(香港)、Michael Tong、Marina Lee 和政府咨询服务(详见致谢)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/885f/7673299/1cc72945eb13/gr4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/885f/7673299/dc2a129813db/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/885f/7673299/1cc72945eb13/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/885f/7673299/fd0a8cf0c66d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/885f/7673299/b90381ab88b2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/885f/7673299/dc2a129813db/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/885f/7673299/1cc72945eb13/gr4.jpg

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[1]
Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study.

Lancet Microbe. 2020-5

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