Title:
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Antibody seroprevalence in the epicenter Wuhan Hubei and six selected provinces after containment of the first epidemic wave of COVID-19 in China |
Abstract:
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BACKGROUND: China implemented containment measures to stop SARS-CoV-2 transmission in response to the COVID-19 epidemic. After the first epidemic wave we conducted population-based serological surveys to determine extent of infection risk factors for infection and neutralization antibody levels to assess the real infections in the random sampled population. METHODS: We used a multistage stratified cluster random sampling strategy to conduct serological surveys in three areas - Wuhan Hubei Province outside Wuhan and six provinces selected on COVID-19 incidence and containment strategy. Participants were consenting individuals >1 year old who resided in the survey area >14 days during the epidemic. Provinces screened sera for SARS-CoV-2-specific IgM IgG and total antibody by two lateral flow immunoassays and one magnetic chemiluminescence enzyme immunoassay; positive samples were verified by micro-neutralization assay. FINDINGS: We enrolled 34857 participants (overall response rate 92%); 427 were positive by micro-neutralization assay. Wuhan had the highest weighted seroprevalence (443% 95% confidence interval [95%CI]=348%-562%) followed by Hubei-ex-Wuhan (044% 95%CI=026%-076%) and the other provinces (<01%). Living in Wuhan (adjusted odds ratio aOR=1370 95%CI= 7912375) contact with COVID-19 patients (aOR=735 95%CI=5051069) and age over 40 (aOR=136 95%CI=107172) were significantly associated with SARS-CoV-2 infection. Among seropositives 101 (24%) reported symptoms and had higher geometric mean neutralizing antibody titers than among the 326 (76%) without symptoms (3024 vs 1521 p<0001). INTERPRETATION: The low overall extent of infection and steep gradient of seropositivity from Wuhan to the outer provinces provide evidence supporting the success of containment of the first wave of COVID-19 in China. SARS-CoV-2 infection was largely asymptomatic emphasizing the importance of active case finding and physical distancing. Virtually the entire population of China remains susceptible to SARS-CoV-2; vaccination will be needed for long-term protection. FUNDING: This study was supported by the Ministry of Science and Technology (2020YFC0846900) and the National Natural Science Foundation of China (82041026 82041027 82041028 82041029 82041030 82041032 82041033). |
Published:
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2021-02-05 |
Journal:
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Lancet Reg Health West Pac |
DOI:
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10.1016/j.lanwpc.2021.100094 |
DOI_URL:
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http://doi.org/10.1016/j.lanwpc.2021.100094 |
Author Name:
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Li Zhongjie |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/li_zhongjie |
Author Name:
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Guan Xuhua |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/guan_xuhua |
Author Name:
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Mao Naiying |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/mao_naiying |
Author Name:
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Luo Huiming |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/luo_huiming |
Author Name:
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Qin Ying |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/qin_ying |
Author Name:
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He Na |
Author link:
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https://covid19-data.nist.gov/pid/rest/local/author/he_na |
Author Name:
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Zhu Zhen |
Author link:
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https://covid19-data.nist.gov/pid/rest/local/author/zhu_zhen |
Author Name:
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Yu Jianxing |
Author link:
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https://covid19-data.nist.gov/pid/rest/local/author/yu_jianxing |
Author Name:
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Li Yu |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/li_yu |
Author Name:
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Liu Jianhua |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/liu_jianhua |
Author Name:
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An Zhijie |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/an_zhijie |
Author Name:
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Gao Wenjing |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/gao_wenjing |
Author Name:
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Wang Xiaoli |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/wang_xiaoli |
Author Name:
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Sun Xiaodong |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/sun_xiaodong |
Author Name:
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Song Tie |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/song_tie |
Author Name:
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Yang Xingfen |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/yang_xingfen |
Author Name:
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Wu Ming |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/wu_ming |
Author Name:
|
Wu Xianping |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/wu_xianping |
Author Name:
|
Yao Wenqing |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/yao_wenqing |
Author Name:
|
Peng Zhibin |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/peng_zhibin |
Author Name:
|
Sun Junling |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/sun_junling |
Author Name:
|
Wang Liping |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/wang_liping |
Author Name:
|
Guo Qing |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/guo_qing |
Author Name:
|
Xiang Nijuan |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/xiang_nijuan |
Author Name:
|
Liu Jun |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/liu_jun |
Author Name:
|
Zhang Bike |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/zhang_bike |
Author Name:
|
Su Xuemei |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/su_xuemei |
Author Name:
|
Rodewald Lance |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/rodewald_lance |
Author Name:
|
Li Liming |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/li_liming |
Author Name:
|
Xu Wenbo |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/xu_wenbo |
Author Name:
|
Shen Hongbing |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/shen_hongbing |
Author Name:
|
Feng Zijian |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/feng_zijian |
Author Name:
|
Gao George F |
Author link:
|
https://covid19-data.nist.gov/pid/rest/local/author/gao_george_f |
sha:
|
c735fd8a07cce1668cb31fc24d174b1d3787e449 |
license:
|
no-cc |
license_url:
|
[no creative commons license associated] |
source_x:
|
Elsevier; Medline; PMC |
source_x_url:
|
https://www.elsevier.com/https://www.medline.com/https://www.ncbi.nlm.nih.gov/pubmed/ |
pubmed_id:
|
33585828 |
pubmed_id_url:
|
https://www.ncbi.nlm.nih.gov/pubmed/33585828 |
pmcid:
|
PMC7864613 |
pmcid_url:
|
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864613 |
url:
|
https://api.elsevier.com/content/article/pii/S2666606521000031
https://doi.org/10.1016/j.lanwpc.2021.100094
https://www.sciencedirect.com/science/article/pii/S2666606521000031
https://www.ncbi.nlm.nih.gov/pubmed/33585828/ |
has_full_text:
|
TRUE |
Keywords Extracted from Text Content:
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Wuhan
SARS-CoV-2
COVID-19
COVID-19 patients
outer
ZL
bal-anced
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specimens
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GMT
appendix pp 6-9
appendix p 20
GMTs
outer
taste
LFA
Wuhan [8
IgG
IgM
Wuhan,
participants
CIs
−40 °C
−0
LW, QG
persons 20-39
−5
Wuhan City
NT tests
ZP
BALF
NPIs
1-81year-olds
LL
Wuhan)
appendix p 15
IgG antibody
patients
coronavirus 2
Hubei
Hubei (
−100
residents
WX
appendix pp 2-4
Lines
LL, HS
NIVDC
COVID-19 patients
ZA
serum samples
Lockdown
WY
HS, NH
sera
ZZ
NAb ≥ 4
Innovita 2019-nCoV antibody
samples
subject-perceived
LL, HS, NH
Vaccines
17-August 16) [29] [30] [31] [32] [33]
blood donors
respondents
children
SARS-CoV-2-specific IgG
NAb plus 3
LR
HL
Hubei.
10,632
throat
COVID-19
appendix p 16
PUE
Wuhan
Hubei's
people
measles
bronchoaveolar lavage fluids
appendix pp [17] [18]
immunodeficiency
−58
JY
NAb
UN2814
SARS-CoV-2-specific NAb
first-wave
NAb GMTs
SARS-CoV-2-specific neutralizing antibodies
Wuhan [16
Spain's
shortness-of-breath
-Wuhan
blood samples
human
WG
±2 • 1
appendix pp 9-10
−2
XG
persons
Hubeiex-Wuhan
SARS-CoV-2
Jiangsu
SARS-CoV-2-specific neutralizing antibody
Hubei-ex-Wuhan
NX, JL
coronavirus
COVID-19 vaccines
appendix p 6
Wuhan
-Wuhan
sera
IgG
Hubei-ex-Wuhan
COVID-19
participants
Hubei Province
SARS-CoV-2-specific IgM
county-
lateral |
Extracted Text Content in Record:
|
First 5000 Characters:Background: China implemented containment measures to stop SARS-CoV-2 transmission in response to the COVID-19 epidemic. After the first epidemic wave, we conducted population-based serological surveys to determine extent of infection, risk factors for infection, and neutralization antibody levels to assess the real infections in the random sampled population. * Corresponding authors. 1 These authors contributed equally to this project. The Lancet Regional Health -Western Pacific 8 (2021) 10 0 094 provinces ( < 0 • 1%). Living in Wuhan (adjusted odds ratio aOR = 13 • 70, 95%CI = 7 • 91-23 • 75), contact with COVID-19 patients (aOR = 7 • 35, 95%CI = 5 • 05-10 • 69), and age over 40 (aOR = 1 • 36, 95%CI = 1 • 07-1 • 72) were significantly associated with SARS-CoV-2 infection. Among seropositives, 101 (24%) reported symptoms and had higher geometric mean neutralizing antibody titers than among the 326 (76%) without symptoms (30 ±2 • 4 vs 15 ±2 • 1, p < 0 • 001).
Interpretation: The low overall extent of infection and steep gradient of seropositivity from Wuhan to the outer provinces provide evidence supporting the success of containment of the first wave of COVID-19 in China. SARS-CoV-2 infection was largely asymptomatic, emphasizing the importance of active case finding and physical distancing. Virtually the entire population of China remains susceptible to SARS-CoV-2; vaccination will be needed for long-term protection.
gies to safely immunize populations and enable selective lifting of non-pharmaceutical interventions that are currently maintaining elimination of SARS-CoV-2 transmission. Prevention and control of COVID-19 will be a long-term effort, requiring considerable domestic work and effective global collaboration.
Evidence before this study Accurately measuring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in populations can help increase knowledge about immunity, transmission, response strategies, surveillance, and eventually vaccination of COVID-19. We searched PubMed for peer-reviewed articles on September 28, 2020, with no limitations of start date or language, using the terms, "COVID-19 , "SARS-CoV-2 , "antibody", "seroprevalence", and "seroepidemiology". Most serosurveys used convenience samples in hospital settings or were conducted among selected populations such as health care workers, blood donors, factory workers, or local community residents, limiting their ability to provide unbiased population seroprevalence estimates. Few studies were conducted immediately following containment of a COVID-19 epidemic, limiting comparability of containment by country or region.
Added value of this study Between two and three weeks after the end of the first-wave of COVID-19 in China, we conducted population-based serological surveys to estimate prevalence of SARS-CoV-2-specific neutralizing antibodies (NAbs) among representative samples totaling 34,857 participants. We surveyed three areas -Wuhan City, Hubeiex-Wuhan, and six provinces selected on the basis of containment strategy and COVID-19 incidence to ensure inclusion of the highest incidence provinces. Resulting seroprevalence estimates were: Wuhan, 4 • 43%; Hubei-ex-Wuhan, 0 • 44%; and the six other provinces, < 0 • 1%. Seroprevalence was highly correlated with reported COVID-19 incidence. Most subjects with serologic evidence of infections were asymptomatic (76%). To our knowledge, this is the first nationally representative estimate of SARS-CoV-2 seroprevalence in China.
Implications of all the available evidence The low overall seroprevalence, the steep gradient of seropositivity from Wuhan to Hubei-ex-Wuhan to the other provinces, and the high correlation with COVID-19 incidence provide evidence supporting the impact of China's centrally-coordinated, locallyimplemented, "whole-of-government, whole-of-society" effort to contain the coronavirus. The low seroprevalence shows that the first wave of COVID-19 infected a relatively small number of individuals in China, leaving virtually the entire population susceptible to SARS-CoV-2 infection. That most infections were asymptomatic supports the importance of contact tracing strategies to stop transmission. Long-term protection of the population and the economy will necessitate using COVID-19 vaccination strate-
In late December 2019, a cluster of patients with severe pneumonia of unknown etiology (PUE) was reported. A new coronavirus, now called SARS-CoV-2, was discovered in the PUE patients' bronchoaveolar lavage fluids (BALF), identified, and sequenced, and was reported to the World Health Organization (WHO) [1] [2] [3] . SARS-CoV-2 is highly contagious, and its human disease, COVID-19, causes significant morbidity and mortality [4] . WHO declared COVID-19 as a pandemic on March 11, 2020 , and by the end of November, there have been over 62 million cases and 1.4 million deaths reported worldwide [5] .
China took unprecedented stringent measures in respon |
Keywords Extracted from PMC Text:
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CIs
ZL
people
shortness-of-breath
CI=0•26%−0•76
SARS-CoV-2′′
Hubei.
GMT
57%−71
WG
Hubei (
4•4
residents
−40 °C
sera
Lockdown
JY
COVID-19′′
immunodeficiency
HS, NH
44%−58
[aOR]=13•70
SARS-CoV-2-specific neutralizing antibodies
UN2814
Wuhan,
WY
appendix p 16
appendix p 15
ZA
NX, JL
33±2•1
subject-perceived
blood donors
ZP
appendix pp 9–10
serum samples
"
NAb
40–59
ZZ
IgG
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appendix p 20
Hubei's
respondents
Wuhan
LL, HS, NH
human
Hubei-ex-Wuhan
blood samples
LFA
throat
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XG
NAb GMTs
SARS-CoV-2-specific neutralizing antibody
XY
lateral
NIVDC
SARS-CoV-2-specific NAb
HL
first-wave
COVID-19 patients
persons
WX
LL
PUE
blood
measles
GMTs
CI=5•05–10•69
CI=1•07–1•72
Jiangsu
Hubei
NAb ≥ 4
NAb plus 3
LW, QG
Wuhan City
SARS-CoV-2-specific IgG
COVID-19 vaccines
SARS-CoV-2
LR
children
appendix pp 6–9
appendix pp 17–18
IgG antibody
Spain's
patients
Wuhan [8
Innovita 2019-nCoV antibody
10,632
specimens
Vaccines
NT tests
LL, HS
coronavirus
Lines"
appendix p 6
taste
13–65
Wuhan)
coronavirus 2
BALF
county-
COVID-19
Wuhan [16
appendix
participants |
Extracted PMC Text Content in Record:
|
First 5000 Characters:Evidence before this study
Accurately measuring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in populations can help increase knowledge about immunity, transmission, response strategies, surveillance, and eventually vaccination of COVID-19. We searched PubMed for peer-reviewed articles on September 28, 2020, with no limitations of start date or language, using the terms, "COVID-19′′, "SARS-CoV-2′′, "antibody", "seroprevalence", and "seroepidemiology". Most serosurveys used convenience samples in hospital settings or were conducted among selected populations such as health care workers, blood donors, factory workers, or local community residents, limiting their ability to provide unbiased population seroprevalence estimates. Few studies were conducted immediately following containment of a COVID-19 epidemic, limiting comparability of containment by country or region.
Added value of this study
Between two and three weeks after the end of the first-wave of COVID-19 in China, we conducted population-based serological surveys to estimate prevalence of SARS-CoV-2-specific neutralizing antibodies (NAbs) among representative samples totaling 34,857 participants. We surveyed three areas – Wuhan City, Hubei-ex-Wuhan, and six provinces selected on the basis of containment strategy and COVID-19 incidence to ensure inclusion of the highest incidence provinces. Resulting seroprevalence estimates were: Wuhan, 4•43%; Hubei-ex-Wuhan, 0•44%; and the six other provinces, <0•1%. Seroprevalence was highly correlated with reported COVID-19 incidence. Most subjects with serologic evidence of infections were asymptomatic (76%). To our knowledge, this is the first nationally representative estimate of SARS-CoV-2 seroprevalence in China.
Implications of all the available evidence
The low overall seroprevalence, the steep gradient of seropositivity from Wuhan to Hubei-ex-Wuhan to the other provinces, and the high correlation with COVID-19 incidence provide evidence supporting the impact of China's centrally-coordinated, locally-implemented, "whole-of-government, whole-of-society" effort to contain the coronavirus. The low seroprevalence shows that the first wave of COVID-19 infected a relatively small number of individuals in China, leaving virtually the entire population susceptible to SARS-CoV-2 infection. That most infections were asymptomatic supports the importance of contact tracing strategies to stop transmission. Long-term protection of the population and the economy will necessitate using COVID-19 vaccination strategies to safely immunize populations and enable selective lifting of non-pharmaceutical interventions that are currently maintaining elimination of SARS-CoV-2 transmission. Prevention and control of COVID-19 will be a long-term effort, requiring considerable domestic work and effective global collaboration.
In late December 2019, a cluster of patients with severe pneumonia of unknown etiology (PUE) was reported. A new coronavirus, now called SARS-CoV-2, was discovered in the PUE patients' bronchoaveolar lavage fluids (BALF), identified, and sequenced, and was reported to the World Health Organization (WHO) [1], [2], [3]. SARS-CoV-2 is highly contagious, and its human disease, COVID-19, causes significant morbidity and mortality [4]. WHO declared COVID-19 as a pandemic on March 11, 2020, and by the end of November, there have been over 62 million cases and 1.4 million deaths reported worldwide [5].
China took unprecedented stringent measures in response to COVID-19, managing it as a Category A disease (the highest level) with a centrally-coordinated, locally-implemented, "whole-of-government, whole-of-society" effort to contain the virus geographically and stop its transmission. Active case finding and isolation, contact tracing and management were implemented throughout China, and physical distancing measures were implemented in varying degrees depending on local transmission risk [6,7]. Lockdown travel restrictions were implemented for Wuhan City on January 23. After an epidemic surge of two months, the incidence of COVID-19 declined. By the end of March, 81,554 confirmed COVID-19 cases had been reported throughout China - 50,007 from Wuhan [8]. After confirming lack of local transmission, the Chinese government lifted Wuhan travel restrictions on April 8, 2020.
The end of the first wave of the COVID-19 epidemic in the first country affected by the pandemic provides an opportunity to assess the extent of infection of the population following a managed epidemic wave. COVID-19 surveillance and reporting in China mainly relies on polymerase chain reaction (PCR)–based testing of symptomatic individuals and close contacts of the infected persons. However, extent of infection can only be determined by population-based serological surveys, as asymptomatic infections are invisible to symptom-based surveillance, and individuals not seeking medical care would be unlikely to be id |
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