Post-lockdown SARS-CoV-2 nucleic acid screening in nearly ten million residents of Wuhan, China

Abstract

Stringent COVID-19 control measures were imposed in Wuhan between January 23 and April 8, 2020. Estimates of the prevalence of infection following the release of restrictions could inform post-lockdown pandemic management. Here, we describe a city-wide SARS-CoV-2 nucleic acid screening programme between May 14 and June 1, 2020 in Wuhan. All city residents aged six years or older were eligible and 9,899,828 (92.9%) participated. No new symptomatic cases and 300 asymptomatic cases (detection rate 0.303/10,000, 95% CI 0.270–0.339/10,000) were identified. There were no positive tests amongst 1,174 close contacts of asymptomatic cases. 107 of 34,424 previously recovered COVID-19 patients tested positive again (re-positive rate 0.31%, 95% CI 0.423–0.574%). The prevalence of SARS-CoV-2 infection in Wuhan was therefore very low five to eight weeks after the end of lockdown.

Full text

ARTICLE
Post-lockdown SARS-CoV-2 nucleic acid screening
in nearly ten million residents of Wuhan, China
Shiyi Cao1,11, Yong Gan1,11, Chao Wang1,11, Max Bachmann2, Shanbo Wei3, Jie Gong4, Yuchai Huang1,
Tiantian Wang1, Liqing Li5, Kai Lu6, Heng Jiang7,8, Yanhong Gong1, Hongbin Xu1, Xin Shen1, Qingfeng Tian9,
Chuanzhu Lv10✉, Fujian Song 2✉, Xiaoxv Yin1✉& Zuxun Lu 1✉
Stringent COVID-19 control measures were imposed in Wuhan between January 23 and April
8, 2020. Estimates of the prevalence of infection following the release of restrictions could
inform post-lockdown pandemic management. Here, we describe a city-wide SARS-CoV-2
nucleic acid screening programme between May 14 and June 1, 2020 in Wuhan. All city
residents aged six years or older were eligible and 9,899,828 (92.9%) participated. No new
symptomatic cases and 300 asymptomatic cases (detection rate 0.303/10,000, 95% CI
0.270–0.339/10,000) were identified. There were no positive tests amongst 1,174 close
contacts of asymptomatic cases. 107 of 34,424 previously recovered COVID-19 patients
tested positive again (re-positive rate 0.31%, 95% CI 0.423–0.574%). The prevalence of
SARS-CoV-2 infection in Wuhan was therefore very low five to eight weeks after the end of
lockdown.
https://doi.org/10.1038/s41467-020-19802-w OPEN
1Department of Social Medicine and Health Management, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, Hubei, China. 2Norwich Medical School, Faculty of Medicine and Health Science, University of East Anglia, Norwich, UK. 3Wuhan Municipal Health
Commission, Wuhan, Hubei, China. 4Wuhan Centre for Clinical Laboratory, Wuhan, Hubei, China. 5Department of Management Science and Engineering,
School of Economics and Management, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, China. 6Tongji Hospital, Huazhong University
of Science and Technology, Wuhan, Hubei, China. 7Centre for Alcohol Policy Research, School of Psychology and Public Health, La Trobe University,
Melbourne, VIC, Australia. 8Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia. 9School of Public
Health, Zhengzhou University, Zhengzhou, Henan, China. 10 Department of Emergency, Hainan Clinical Research Centre for Acute and Critical Diseases, The
Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
11
These authors contributed equally: Shiyi Cao, Yong Gan, Chao Wang.
✉email: lyuchuanzhu@hainmc.edu.cn;Fujian.song@uea.ac.uk;yxx@hust.edu.cn;zuxunlu@yahoo.com
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The Coronavirus Disease 2019 (COVID-19) was first
reported in December 2019, and was classified as a pan-
demic by the World Health Organization on March 11,
20201. Following strict lockdown measures, the COVID-19 epi-
demic was generally under control in China, and the whole
country has progressed into a post-lockdown phase. In this phase,
countries face new problems and challenges, including how to
accurately assess the post-lockdown risk of the COVID-19 epi-
demic, how to avoid new waves of COVID-19 outbreaks, and
how to facilitate the resumption of economy and normal social
life. As the city most severely affected by COVID-19 in China,
Wuhan had been under lockdown measures from January 23
until April 8, 2020. During the first 2 months after city’s
reopening, there were only a few sporadic COVID-19 cases in
Wuhan (six newly confirmed cases from April 8 to May 10,
20202). However, there was still concern about the risk of
COVID-19 in Wuhan, which seriously affected the resumption of
industrial production and social services, and hampered the
normal lives of residents. In order to ascertain the current status
of the COVID-19 epidemic, the city government of Wuhan car-
ried out a comprehensive citywide nucleic acid screening of
SARS-CoV-2 infection from May 14, 2020 to June 1, 2020.
The citywide screening of SARS-CoV-2 infection in Wuhan is
a mass screening programme in post-lockdown settings, and
provided invaluable experiences or lessons with international
relevance as more countries and cities around the world entering
the post-lockdown phase. In this study, we report the organisa-
tion process, detailed technical methods used, and results of this
citywide nucleic acid screening.
Results
There were 10,652,513 eligible people aged ≥6 years in Wuhan
(94.1% of the total population). The nucleic acid screening was
completed in 19 days (from May 14, 2020 to Jun 1, 2020), and
tested a total of 9,899,828 persons from the 10,652,513 eligible
people (participation rate, 92.9%). Of the 9899,828 participants,
9,865,404 had no previous diagnosis of COVID-19, and 34,424
were recovered COVID-19 patients.
The screening of the 9,865,404 participants without a history of
COVID-19 found no newly confirmed COVID-19 cases, and
identified 300 asymptomatic positive cases with a detection rate of
0.303 (95% CI 0.270–0.339)/10,000. The median age-stratified Ct-
values of the asymptomatic cases were shown in Supplementary
Table 1. Of the 300 asymptomatic positive cases, two cases came
from one family and another two were from another family.
There were no previously confirmed COVID-19 patients in these
two families. A total of 1174 close contacts of the asymptomatic
positive cases were traced, and they all tested negative for the
COVID-19. There were 34,424 previously recovered COVID-19
cases who participated in the screening. Of the 34,424 partici-
pants with a history of COVID-19, 107 tested positive again,
giving a repositive rate of 0.310% (95% CI 0.423–0.574%).
Virus cultures were negative for all asymptomatic positive and
repositive cases, indicating no “viable virus”in positive cases
detected in this study.
All asymptomatic positive cases, repositive cases and their
close contacts were isolated for at least 2 weeks until the
results of nucleic acid testing were negative. None of detected
positive cases or their close contacts became symptomatic or
newly confirmed with COVID-19 during the isolation period.
In this screening programme, single and mixed testing was
performed, respectively, for 76.7% and 23.3% of the collected
samples. The asymptomatic positive rates were 0.321 (95% CI
0.282–0.364)/10,000 and 0.243 (95% CI 0.183–0.315)/10,000,
respectively.
The 300 asymptomatic positive persons aged from 10 to 89
years, included 132 males (0.256/10,000) and 168 females (0.355/
10,000). The asymptomatic positive rate was the lowest in chil-
dren or adolescents aged 17 and below (0.124/10,000), and the
highest among the elderly aged 60 years and above (0.442/10,000)
(Table 1). The asymptomatic positive rate in females (0.355/
10,000) was higher than that in males (0.256/10,000).
The asymptomatic positive cases were mainly domestic and
unemployed residents (24.3%), retired older adults (21.3%), and
public service workers (11.7%) (Fig. 1).
The asymptomatic positive rate in urban districts was on
average 0.456/10,000, ranging from 0.317/10,000 in Hongshan to
0.807/10,000 in Wuchang district. A lower rate of asymptomatic
positive cases was found in suburban districts (0.132/10,000),
ranging from 0.047/10,000 in Xinzhou to 0.237/10,000 in Jiangan
district (Fig. 2).
Among the 7280 residential communities in Wuhan, asymp-
tomatic positive cases were identified in 265 (3.6%) communities
(only one case detected in 246 communities), while no asymp-
tomatic positive cases were found in other 96.4% communities.
Testing of antibody against SARS-CoV-2 virus was positive
IgG (+) in 190 of the 300 asymptomatic cases, indicating that
63.3% (95% CI 57.6–68.8%) of asymptomatic positive cases were
actually infected. The proportion of asymptomatic positive cases
with both IgM (−) and IgG (−) was 36.7% (95% CI: 31.2–42.4%;
n=110), indicating the possibility of infection window or false
positive results of the nucleic acid testing (Table 2).
Higher detection rates of asymptomatic infected persons were
in Wuchang, Qingshan and Qiaokou districts, and the prevalence
of previously confirmed COVID-19 cases were 68.243/10,000,
53.767/10,000, and 100.047/10,000, respectively, in the three
districts. Figure 3shows that districts with a high detection rate of
asymptomatic positive persons generally had a high prevalence of
confirmed COVID-19 cases (r
s
=0.729, P=0.002).
Discussion
The citywide nucleic acid screening of SARS-CoV-2 infection in
Wuhan recruited nearly 10 million people, and found no newly
confirmed cases with COVID-19. The detection rate of asymp-
tomatic positive cases was very low, and there was no evidence of
transmission from asymptomatic positive persons to traced close
contacts. There were no asymptomatic positive cases in 96.4% of
the residential communities.
Previous studies have shown that asymptomatic individuals
infected with SARS-CoV-2 virus were infectious3, and might
subsequently become symptomatic4. Compared with sympto-
matic patients, asymptomatic infected persons generally have low
quantity of viral loads and a short duration of viral shedding,
which decrease the transmission risk of SARS-CoV-25. In the
present study, virus culture was carried out on samples from
asymptomatic positive cases, and found no viable SARS-CoV-2
virus. All close contacts of the asymptomatic positive cases tested
negative, indicating that the asymptomatic positive cases detected
in this study were unlikely to be infectious.
There was a low repositive rate in recovered COVID-19
patients in Wuhan. Results of virus culturing and contract tracing
found no evidence that repositive cases in recovered COVID-19
patients were infectious, which is consistent with evidence from
other sources. A study in Korea found no confirmed COVID-19
cases by monitoring 790 contacts of 285 repositive cases6.
The official surveillance of recovered COVID-19 patients in
China also revealed no evidence on the infectiousness of reposi-
tive cases7. Considering the strong force of infection of COVID-
198–10, it is expected that the number of confirmed cases is
associated with the risk of being infected in communities. We
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found that asymptomatic positive rates in different districts of
Wuhan were correlated with the prevalence of previously con-
firmed cases. This is in line with the temporal and spatial evo-
lution (especially the long-tailed characteristic) of infectious
diseases11.
Existing laboratory virus culture and genetic studies9,10 showed
that the virulence of SARS-CoV-2 virus may be weakening over
time, and the newly infected persons were more likely to be
asymptomatic and with a lower viral load than earlier infected
cases. With the centralized isolation and treatment of all COVID-
19 cases during the lockdown period in Wuhan, the risk of
residents being infected in the community has been greatly
reduced. When susceptible residents are exposed to a low dose of
virus, they may tend to be asymptomatic as a result of their own
immunity. Serological antibody testing in the current study found
that at least 63% of asymptomatic positive cases were actually
infected with SARS-CoV-2 virus. Nonetheless, it is too early to be
complacent, because of the existence of asymptomatic positive
cases and high level of susceptibility in residents in Wuhan.
Public health measures for the prevention and control of COVID-
19 epidemic, including wearing masks, keeping safe social dis-
tancing in Wuhan should be sustained. Especially, vulnerable
populations with weakened immunity or co-morbidities, or both,
should continue to be appropriately shielded.
Findings from this study show that COVID-19 was well con-
trolled in Wuhan at the time of the screening programme. After
two months since the screening programme (by August 9, 2020),
there were no newly confirmed COVID-19 cases in Wuhan.
Table 1 Characteristics of asymptomatic positive individuals.
Total (%) Asymptomatic positive persons (%) Detection rate per 10,000 (95% CI) Pvalue
Total 9,899,828 (100.0) 300 (100.0) 0.303 (0.270–0.339)
Sex
Male 5,162,960 (52.2) 132 (44.0) 0.256 (0.214–0.303) 0.005
Female 4,736,868 (47.8) 168 (56.0) 0.355 (0.303–0.413
Age (years old)
≤17 969,014 (9.8) 12 (4.0) 0.124 (0.064–0.216) <0.001
18–44 4,448,230 (44.9) 104 (34.7) 0.234 (0.191–0.283)
45–59 2,492,943 (25.2) 96 (32.0) 0.385 (0.312–0.470)
≥60 1,989,641 (20.1) 88 (29.3) 0.442 (0.355–0.545)
Administrative Districts in Wuhan
Wuchang 904,636 (9.1) 73 (24.3) 0.807 (0.633–1.015) <0.001
Qingshan 414,312 (4.2) 23 (7.7) 0.555 (0.352–0.833)
Qiaokou 583,440 (5.9) 32 (10.7) 0.548 (0.375–0.774)
Hanyang 717,429 (7.2) 29 (9.7) 0.404 (0.271–0.581)
Jianghan 524,224 (5.3) 19 (6.3) 0.362 (0.218–0.566)
Hongshan 1,103,079 (11.1) 35 (11.7) 0.317 (0.221–0.441)
East Lake High-tech Development Area 782,987 (7.9) 19 (6.3) 0.243 (0.146–0.379)
Jiangan 800,440 (8.1) 19 (6.3) 0.237 (0.143–0.371)
Caidian 503,595 (5.1) 11 (3.7) 0.218 (0.109–0.391)
Jiangxia 671,248 (6.8) 14 (4.7) 0.209 (0.114–0.350)
Huangpi 979,920 (9.9) 14 (4.7) 0.143 (0.078–0.240)
Hannan 417,022 (4.2) 4 (1.3) 0.096 (0.026–0.246)
Dongxihu 777,204 (7.9) 5 (1.7) 0.064 (0.021–0.150)
Xinzhou 634,408 (6.4) 3 (1.0) 0.047 (0.010–0.138)
East Lake Scenic Area of Wuhan 85,884 (0.9) 0 (0.0) 0.000 (0.000–0.430)
χ2test was used to assess the association between the detection rate of asymptomatic cases increased and sex and age. Urban districts of Wuhan includes Wuchang, Qingshan, Qiaokou, Hanyang,
Jiangan, Jianghan, and Hongshan; Suburban districts of Wuhan includes Hannan, Caidian, Dongxihu, Xinzhou, Jiangxia, Huangpi, East Lake High-tech Development Area, and East Lake Scenic Area
of Wuhan.
2, 0.7% 47, 15.7%
13, 4.3%
4, 1.3%
17, 5.7%
19, 6.3%
20, 6.7%
35, 11.7%
64, 21.3%
73, 24.3%
Housework or unemployment
The emeritus and retirees
Service workers in public place
Industrial labourer
Cadres staff
Student
Teacher
Medical staff
Others
Transportation service personnel
Agricultural labourer
6, 2.0%
Fig. 1 The occupation distribution of asymptomatic positive cases (%). Note: Others included the self-employed, military personnel, and so on. (Source
data are provided as s Source Data file.).
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Further testing of SARS-CoV-2 in samples collected from market
environment settings in Wuhan were conducted, and found no
positive results after checking a total of 52,312 samples from 1795
market setting during June 13 to July 2, 202012.
This study has several limitations that need to be discussed.
First, this was a cross-sectional screening programme, and we are
unable to assess the changes over time in asymptomatic positive
and reoperative results. Second, although a positive result of
nucleic acid testing reveals the existence of the viral RNAs, some
false negative results were likely to have occurred, in particular
due to the relatively low level of virus loads in asymptomatic
infected individuals, inadequate collection of samples, and limited
accuracy of the testing technology13. Although the screening
programme provided no direct evidence on the sensitivity and
specificity of the testing method used, a meta-analysis reported a
Huangpi
Dongxihu
Caidian
0.218 Hannan
Hongshan
Qingshan
0.317
0.555
0.096
Jiangxia
0.209
0.064
Xinzhou
0.047
0.143
Detection rate of asymptomatic
patients at District level (per 10,000)
0.000
0 10 Km
0.001–0.100
0.101–0.200
0.201–0.300
0.301–0.400
0.401–0.600
0.601–0.750
Scenic
Fig. 2 The geographic distribution of the detection rate of asymptomatic positive cases. Note: 1 represents Jianghan district; 2 represents Qiaokou
district. (Source data are provided as s Source Data file.).
Table 2 Results of the detection of antibody in 300
asymptomatic positive persons.
IgM IgG Asymptomatic positive persons % (95% CI)
Results
−+161 53.7 (47.8–59.4)
−−110 36.7 (31.2–42.4)
++29 9.7 (6.6–13.6)
+−0 0.0 (0.0–1.2)
“−”indicates negative; “+”indicates positive.
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pooled sensitivity of 73% (95% CI 68–78%) for nasopharayngeal
and throat swab testing of COVID-1914. Testing kits used in the
screening programme were publicly purchased by the govern-
ment and these kits have been widely used in China and other
countries. Multiple measures were taken to possibly minimise
false negative results in the screening programme. For example,
standard training was provided to health works for sample col-
lection to ensure the sample quality. The experiment procedures,
including specimen collection, extraction, PCR, were according to
official guidelines (Supplementary Note 1). For the real-time RT-
PCR assay, two target genes were simultaneously tested. Even so,
false negative results remained possible, particularly in any mass
screening programmes. However, even if test sensitivity was as
low as 50%, then the actual prevalence would be twice as high as
reported in this study, but would still be very low. Around 7.1% of
eligible residents did not participate in the citywide nucleic acid
screening and the screening programme did not collect detailed
data on reasons for nonparticipation, which is a limitation of this
a
b
120.000
100.000
68.243
53.767
100.047
65.124
77.582
46.064
30.571
68.201
25.050
11.097
15.995
26.021
38.937
10.591
31.580
80.000
60.000
Prevalence of previously confirmed
patients (per 10,000)
Detection rate of asymptomatic
infection (per 10,000)
40.000
20.000
0.000
0.900
0.807
0.555 0.548
0.404
0.362
0.317
0.243 0.237 0.218 0.209
0.143
0.096 0.064 0.047
0.000
0.800
0.700
0.600
0.500
0.400
0.300
0.200
0.100
0.000
Wuchang
Qingshan
Qiaokou
Hanyang
Jianghan
Hongshan
Jiangan
Jiangxia
Huangpi
Hannan
Dongxihu
Xinzhou
East Lake Scenic Area
Caidian
East Lake High-tech Development Zone
Wuchang
Qingshan
Qiaokou
Hanyang
Jianghan
Hongshan
Jiangan
Jiangxia
Huangpi
Hannan
Dongxihu
Xinzhou
East Lake Scenic Area
Caidian
East Lake High-tech Development Zone
Fig. 3 The prevalence of previously confirmed patients and the detection rate of asymptomatic positive cases of COVID-19 in each district in Wuhan.
aThe prevalence of previously confirmed patients of COVID-19 in each district in Wuhan. bThe detection rate of asymptomatic positive cases of COVID-
19 in each district in Wuhan. (Source data are provided as s Source Data file.).
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study. Although there were no official statistics, a large number of
migrant workers and university students left Wuhan before the
lockdown, joining their families in other cities or provinces for
traditional Chinese New Year. Therefore, it is likely that most
nonparticipants were not in Wuhan at the time of the screening.
The main objective of the screening programme was to assess the
risk of COVID-19 epidemic in residents who were actually living
in the post-lockdown Wuhan. Therefore, the estimated positive
rates are unlikely to be materially influenced by nonparticipation
of residents who were not in Wuhan or some residents who did
not participate in the screening for other reasons. Moreover,
people who left Wuhan were the target population for monitoring
in other provinces and cities and were required to take nucleic
acid testing. Although there was no official statistics showing the
positive rate of nucleic acid testing in this population, there was
no report that shown a higher positive rate of nucleic acid testing
than our findings.
In summary, the detection rate of asymptomatic positive cases
in the post-lockdown Wuhan was very low (0.303/10,000), and
there was no evidence that the identified asymptomatic positive
cases were infectious. These findings enabled decision makers to
adjust prevention and control strategies in the post-lockdown
period. Further studies are required to fully evaluate the impacts
and cost-effectiveness of the citywide screening of SARS-CoV-2
infections on population’s health, health behaviours, economy,
and society.
Methods
Study population and ethical approvals. Wuhan has about 11 million residents
in total, with seven urban and eight suburban districts. Residents are living in 7280
residential communities (or residential enclosures, “xiao-qu”in Chinese), and each
residential community could be physically isolated from other communities for
preventing transmission of COVID-19.
The screening programme recruited residents (including recovered COVID-19
patients) currently living in Wuhan who were aged ≥6 years (5,162,960 males, 52.2%).
All participants provided written or verbal informed consent after reading a statement
that explained the purpose of the testing. For participants who aged 6–17 years old,
consent was obtained from their parents or guardians. The study protocol for an
evaluation of the programme based on anonymized screening data was approved by the
Ethics Committee of the Tongji Medical College Institutional Review Board, Huazhong
University of Science and Technology, Wuhan, China (No. IROG0003571).
Organizational guarantee and community mobilization. A citywide nucleic acid
screening group was formed, with specialized task teams contributing to com-
prehensive coordination, technical guidance, quality control, participation invita-
tion, information management, communication, and supervision of the screening.
The city government invested 900 million yuan (RMB) in the testing programme.
From 14 May to 1 June 2020, in the peak time, up to 2907 sample collection sites
were functioning at the same time in Wuhan. Each sample collection site had an
assigned sample collection group, including several health professionals (staffed
according to the number of communities’residents), 2–4 community managers,
1–2 police officers, and 1–2 inspectors. The sampling sites were set up based on the
number and accessibility of local residents. Local community workers were
responsible for a safe and orderly sampling process to minimise the waiting time.
In addition, mobile sampling teams were formed by primary health care profes-
sionals and volunteers to conduct door-to-door sampling for residents who had
physical difficulties or were unable to walk.
About 50,000 health professionals (mainly doctors and nurses from community
health centers) and more than 280,000 person-times of community workers and
volunteers contributed to sample collection, transport of equipment and samples
collected, arrangement of participation process, and maintaining order of sampling
sites. Public information communication and participant invitation were
implemented through mass media, mobile messages, WeChat groups, and
residential community broadcasts, so as to increase residents’awareness and the
participation.
Acquisition, preservation, and transport of samples. All sampling personnel
received standard training for the collection of oropharyngeal swab samples. To
minimise the risk of cross-infection, the sampling process strictly followed a dis-
infection process and environmental ventilation were ensured. The collected
samples were stored in a virus preservation solution or immersed in isotonic saline,
tissue culture solution, or phosphate buffer (Supplementary note 1). Then, all
samples were sent to testing institutions within 4 h using delivery boxes for
biological samples refrigerated with dry ice to guarantee the stability of nucleic acid
samples.
Technical methods for laboratory testing of collected samples. A total of 63
nucleic acid testing laboratories, 1451 laboratory workers and 701 testing equip-
ment were involved in the nucleic acid testing. Received samples were stored at
4 °C and tested within 24 h of collection. Any samples that could not be tested
within 24 h were stored at −70 °C or below (Supplementary note 1). In addition to
“single testing”(i.e., separate testing of a single sample), “mixed testing”was also
performed for 23% of the collected samples to increase efficiency, in which five
samples were mixed in equal amounts, and tested in the same test tube. If a mixed
testing was positive for COVID-19, all individual samples were separately retested
within 24 h15.
Details regarding technical methods for sequencing and virus culture were
provided in Supplementary note 1. Real-time reverse transcriptase-polymerase
chain reaction (RT-PCR) assay method was used for the nucleic acid testing. We
simultaneously amplified and tested the two target genes: open reading frame 1ab
(ORF1ab) and nucleocapsid protein (N) (Supplementary Note 1). A cycle threshold
value (Ct-value) less than 37 was defined as a positive result, and no Ct-value or a
Ct-value of 40 or more was defined as a negative result. For Ct-values ranging from
37 to 40, the sample was retested. If the retest result remained less than 40 and the
amplification curve had obvious peak, the sample was classified as positive;
otherwise, it was reported as being negative. These diagnostic criteria were based
on China’sofficial recommendations16.
For asymptomatic positive cases, virus culture was carried out in biosafety level-
3 laboratories. The colloidal gold antibody test was also performed for
asymptomatic positive cases (Supplementary note 1). All testing results were
double entered into a specifically designed database, and managed by the Big Data
and Investigation Group of the COVID-19 Prevention and Control Centre in
Wuhan, which was established to collect and manage data relevant to the COVID-
19 epidemic.
Participant data collection and management. Before sample collection, residents
electronically (using a specifically designed smartphone application) self-uploaded
their personal information, including ID number, name, sex, age, and place of
residence. Then, the electronic machine system generated a unique personal bar-
code and stuck it on the sample tube to ensure the match between the sample and
the participant. Then trained staff interviewed each individual regarding the history
of COVID-19 and previous nucleic acid testing. There was a database of confirmed
COVID-19 cases in Wuhan, which can be used to validate the self-reported pre-
vious COVID-19 infection. All information was entered into a central database.
The testing results were continually uploaded to the central database by testing
institutions. Contact tracing investigations were conducted on participants who
tested positive for SARS-CoV-2, to track and manage their close contacts. The pre-
existing unique identification code for each resident was used as the programme’s
identification number, to ensure information accuracy during the whole process of
screening, from sampling, nucleic acid testing, result reporting, the isolation of
detected positive cases, and tracing of close contacts of positive cases. All screening
information was kept strictly confidential and was not allowed to be disclosed or
used for other purposes other than clinical and public health management. Per-
sonal information of asymptomatic positive cases was only disclosed to designated
medical institutions and community health centres for the purpose of medical
isolation and identification of close contacts. Researcher was blind to the study
hypothesis during data collection.
Biological security guarantee. Nucleic acid testing was performed in biosafety
level-2 (BSL-2) laboratories, and virus culture was conducted in biosafety level-3
laboratories. Sampling and testing personnel adopted the personal protective
measures according to the standard of biosafety level-3 laboratories. Participating
laboratories implemented control measures to guarantee biological safety in
accordance with relevant regulations17.
Result query and feedback. Two to three days after sample collection, partici-
pants could inquire about their test results using WeChat or Alipay application by
their unique ID numbers. The results included text descriptions of nucleic acid
testing and coloured health codes. A green coloured health code refers to a negative
result, and a red coloured health code indicates a positive result.
Definition and management of identified confirmed cases and close contacts.
In this study, all confirmed COVID-19 cases were diagnosed by designated medical
institutions according to National Guidelines for the Prevention and Control of
COVID-19 (Supplementary Note 2). Asymptomatic positive cases referred to
individuals who had a positive result during screening, and they had neither a
history of COVID-19 diagnosis, nor any clinical symptoms at the time of the
nucleic acid testing. Close contacts were individuals who closely contacted with an
asymptomatic positive person since 2 days before the nucleic acid sampling16.
Repositive cases refer to individuals who recovered from previously confirmed
COVID-19 disease and had a positive testing again in the screening programme.
All repositive cases, asymptomatic positive persons, and their close contacts were
ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-19802-w
6NATURE COMMUNICATIONS | (2020) 11:5917 | https://doi.org /10.1038/s41467-020-19802-w | www.nature.c om/naturecommunications
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isolated for at least 2 weeks in designated hotels managed by primary health care
professionals, and they were released from isolation only if two consecutive nucleic
acid tests were negative.
Statistical analysis. Detection rate of asymptomatic positive or repositive cases
was calculated by dividing the number of individuals with a positive result of
nucleic acid testing by the number of participants tested. Because of extremely low
detection rates, we calculated 95% confidence intervals of estimated proportions
using Pearson–Klopper exact method, implemented through R package “binom”
version 1.1-118. SPSS version 22.0 was used for other statistical analyses. We
analyzed the distribution of asymptomatic positive cases and assessed the Spear-
man correlation between the asymptomatic positive rate and the prevalence of
previously confirmed COVID-19 cases in different districts of Wuhan. Differences
in asymptomatic positive rates by sex and age groups were assessed using the χ2
test. ArcGIS 10.0 was used to draw a geographic distribution map of asymptomatic
positive cases. A value of P< 0.05 (two-tailed) was considered statistically
significant.
Reporting summary. Further information on research design is available in the Nature
Research Reporting Summary linked to this article.
Data availability
Detailed data directly used to generate each figure or table of this study are available
within the article, Supplementary Information and source data are provided with
this paper.
Received: 18 August 2020; Accepted: 27 October 2020;
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Acknowledgements
We would like to thank all institutions and all citizens in Wuhan for their support for
citywide nucleic acid screening work. We also would like to thank the Wuhan city
government for this citywide nucleic acid testing, sampling and management, and thank
the big data and investigation group of COVID-19 prevention and control institution in
Wuhan (the data and investigation group of Wuhan Municipal Health Commission) for
their efforts in the data collection. In addition, we would like to thank the National Social
Science Foundation of China (Grant No. 18ZDA085) for supporting the fund.
Author contributions
S.Y.C., C.W., X.X.Y., and Z.X.L. conceived the study. C.W., Y.C.H., T.T.W., K.L., H.B.X.,
and X.S. participated in the acquisition of data. S.B.W. and J.G. were responsible for the
on-site specimen collection, laboratory testing quality evaluation, and control. Y.C.H.,
T.T.W., and L.Q.L. analyzed the data. H.J., Y.H.G., and F.J.S. gave advice on metho-
dology. Q.F.T. and C.Z.L. investigated the responses to the citywide nucleic acid testing
among residents lived in outside of Wuhan city. S.Y.C., Y.G., C.W., and X.X.Y. drafted
the manuscript, Y.G., M.B., and F.J.S. revised the manuscript, and M.B., C.Z.L., and F.J.S.
critically commented and edited the manuscript. All authors read and approved the final
manuscript. Z.X.L. is the guarantor of this study.
Competing interests
The authors declare no competing interests.
Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41467-
020-19802-w.
Correspondence and requests for materials should be addressed to C.L., F.S., X.Y. or Z.L.
Peer review information Nature Communications thanks Junxiong Vincent Pang and
the other, anonymous reviewer(s) for their contribution to the peer review of this work.
Peer review reports are available.
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