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International Journal of Infectious Diseases 101 (2020) 314–322

Contents lists available at ScienceDirect

International Journal of Infectious Diseases


journal homepage: www.elsevier.com/locate/ijid

Review

Population-based seroprevalence surveys of anti-SARS-CoV-2


antibody: An up-to-date review
Chih-Cheng Laia , Jui-Hsiang Wanga , Po-Ren Hsuehb,c,*
a
Department of Internal Medicine, Kaohsiung Veterans General Hospital, Tainan Branch, Tainan, Taiwan
b
Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
c
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

A R T I C L E I N F O A B S T R A C T

Article history: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus
Received 15 September 2020 disease 2019 (COVID-19), has led to a global pandemic. However, the majority of currently available data
Received in revised form 23 September 2020 are restricted to laboratory-confirmed cases for symptomatic patients, and the SARS-CoV-2 infection can
Accepted 4 October 2020
manifest as an asymptomatic or mild disease. Therefore, the true extent of the burden of COVID-19 may
be underestimated. Improved serological detection of specific antibodies against SARS-CoV-2 could help
Keywords: estimate the true numbers of infections. This article comprehensively reviews the associated literature
Antibody
and provides updated information regarding the seroprevalence of the anti-SARS-CoV-2 antibody. The
COVID-19
SARS-CoV-2
seroprevalence can vary across different sites and the seroprevalence can increase with time during
Population-based survey longitudinal follow-up. Although healthcare workers (HCWs), especially those caring for COVID-19
Seroprevalence patients, are considered as a high-risk group, the seroprevalence in HCWs wearing adequate personal
protective equipment is thought to be no higher than that in other groups. With regard to sex, no
statistically significant difference has been found between male and female subjects. Some, but not all,
studies have shown that children have a lower risk than other age groups. Finally, seroprevalence can vary
according to different populations, such as pregnant women and hemodialysis patients; however, limited
studies have examined these associations. Furthermore, the continued surveillance of seroprevalence is
warranted to estimate and monitor the growing burden of COVID-19.
© 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).

Introduction proteins, RNA-dependent RNA polymerase genes, and the N1,


N2, and N3 target genes, among suspected cases with an exposure
Even though severe acute respiratory syndrome coronavirus history and signs/symptoms of SARS-CoV-2 infection (Lai et al.,
2 (SARS-CoV-2) only emerged at the end of 2019, the associated 2020c). However, the clinical manifestations of COVID-19 include
disease–coronavirus disease 2019 (COVID-19)–has spread rap- both respiratory and extra-respiratory signs and symptoms and
idly to more than 180 countries/regions worldwide and has can range from an asymptomatic mild disease to severe disease/
consequently led to a global pandemic (World Health Organiza- acute respiratory tract infections (Lai et al., 2020d, 2020e; Li et al.,
tion (WHO), 2020). As of September 7, 2020, nearly 27 million 2020a, b). Therefore, misdiagnosis of COVID-19 can occur in
COVID-19 cases have been reported worldwide, causing 876,616 patients without a characteristic presentation, even for asymp-
deaths, with an associated case fatality rate of 3.3% (World tomatic and mild infections, and in places where qRT-PCR is
Health Organization (WHO), 2020; Lai et al., 2020a, b; Sheng unavailable. These issues could limit our understanding of the
et al., 2020). extent of SARS-CoV-2 infection and further affect the implemen-
Currently, the diagnosis of COVID-19 is confirmed by the tation of infection control and prevention policies.
detection of SARS-CoV-2 via real-time reverse transcription To resolve this issue, the use of a serological test to detect anti-
polymerase chain reaction (qRT-PCR) assays that target open SARS-CoV-2 antibodies could be a better way to estimate the
reading frame-1 antibodies, envelope proteins, nucleocapsid burden of SARS-CoV-2 infection than the PCR method, and help
improve understanding of the associated epidemiology (Lai et al.,
2020c; Eckerle and Meyer, 2020; Ko et al., 2020; Lee et al., 2020a,
Lee et al., 2020b). Hence, this review was conducted to provide
* Corresponding author at: Department of Laboratory Medicine, National Taiwan
University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. updated and comprehensive information about the seroprevalence
E-mail address: [email protected] (P.-R. Hsueh). of the SARS-CoV-2 antibody in different populations.

https://doi.org/10.1016/j.ijid.2020.10.011
1201-9712/© 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C.-C. Lai, J.-H. Wang and P.-R. Hsueh International Journal of Infectious Diseases 101 (2020) 314–322

Population-based seroprevalence studies In France, 998 samples collected from blood donors during the
last week of March or the first week of April 2020 were tested for
Europe neutralizing antibodies against SARS-CoV-2, and the overall
seroprevalence was found to be low (2.7%, n = 27) (Gallian et al.,
Several large population-based studies have been conducted 2020). By contrast, a more updated surveillance conducted
in COVID-19 hotspots (Pollán et al., 2020; Stringhini et al., 2020; between May 4 and June 23, 2020 in France showed higher
Fiore et al., 2020; Vena et al., 2020; Gallian et al., 2020; adjusted estimates of seroprevalence (positive anti-SARS-CoV-2
Bogogiannidou et al., 2020; Silveira et al., 2020; Amorim Filho ELISA IgG result against the spike protein of SARS-CoV-2), with
et al., 2020; Sood et al., 2020; Ng et al., 2020; Rosenberg et al., values of 10.0% (95% CI 9.1–10.9%) and 9.0% (95% CI 7.7–10.2%) in
2020; Havers et al., 2020; Nir et al., 2020; Sutton et al., 2020; Ile-de-France and Grand Est, respectively–two regions with high
McLaughlin et al., 2020; Naranbhai et al., 2020; Xu et al., 2020; rates of COVID-19–and of 3.1% (95% CI 2.4–3.7%) in Nouvelle
Chughtai et al., 2020; Younas et al., 2020; Sam et al., 2020). In Aquitaine–a region with a low rate of COVID-19 (Carrat et al.,
Spain, a nationwide, population-based sero-epidemiological 2020). Moreover, they noted that confinement was associated with
study was conducted from April 27 to May 11, 2020 (Encuesta a higher seroprevalence, but that a lower seroprevalence was
Seroepidemiológica de la Infección por el Virus SARS-COV-2 en observed in smokers compared to non-smokers (Carrat et al.,
España; ENE-COVID). In that study, 202,35,883 households were 2020).
initially selected from the municipal rolls, using a two-stage During the early stage in Greece, the positive rate of anti-SARS-
random sampling method with stratification by province and CoV-2 IgG was only 0.36% (n = 24) among 6586 serum samples, and
municipality size. A total of 61,075 participants received the the crude prevalence was 0.24% (5/2075) in March and 0.42% (19/
point-of-care test (Orient Gene Biotech COVID-19 IgG/IgM Rapid 4511) in April (Bogogiannidou et al., 2020).
Test Cassette; Zhejiang Orient Gene Biotech, Zhejiang, China;
reference GCCOV-402a), and among them, 51,958 further received America
a chemiluminescent microparticle immunoassay for the qualita-
tive detection of IgG against SARS-CoV-2 nucleoprotein (SARS- In Brazil, three rounds of probability sample household surveys
CoV-2 IgG for use with ARCHITECT; Abbott Laboratories, Abbott in the state of Rio Grande do Sul were conducted in nine large
Park, IL, USA; reference 06R8620). The seroprevalence was found municipalities using the Wondfo lateral flow point-of-care test for
to be 5.0% (95% confidence interval (CI) 4.7–5.4%) by the point-of- IgM and IgG against SARS-CoV-2 (https://en.wondfo.com.cn/
care test and 4.6% (95% CI 4.3–5.0%) by the immunoassay, with a product/wondfo-sars-cov-2-antibody-test-lateral-flow-method-
specificity–sensitivity range of 3.7% (95% CI 3.3–4.0%; both tests 2/). The seroprevalence was estimated to be 0.048% (2/4151; 95% CI
positive) to 6.2% (95% CI 5.8–6.6%; either test positive) (Pollán 0.006–0.174%) during April 11–13, 2020 (round 1), 0.135% (6/4460;
et al., 2020). 95% CI 0.049–0.293%) during April 25–27, 2020 (round 2), and
A study in Switzerland reported the preliminary results of the 0.222% (10/4500; 95% CI 0.107–0.408%) during May 9–11, 2020
surveillance of 2766 participants from 1339 households, with a (round 3) (Silveira et al., 2020). Furthermore, a significant upward
demographic distribution similar to that of the canton of Geneva, trend was observed throughout the surveys (Silveira et al., 2020).
between April 6 and May 9, 2020 (Stringhini et al., 2020). In that Another study (Amorim Filho et al., 2020) included 2857 blood
study, 12 weekly seroprevalence surveys, using a commercially donors in Rio de Janeiro, Brazil from April 14 to April 27, 2020 and
available ELISA (Euroimmun; Lübeck, Germany; #EI 2606-9601 G) used MedTest Coronavirus 2019-nCoV IgG/IgM (MedLevensohn;
targeting the S1 domain of the spike protein of SARS-CoV-2 (serum Yuhang District, China), an immunochromatographic assay li-
diluted 1:101), were processed on a EUROLabWorkstation ELISA censed by the Brazilian Health Surveillance Agency (ANVISA) in
(Euroimmun) (SEROCoV-POP study). The results estimated the March 2020 (https://consultas.anvisa.gov.br/#/saude/q/?numer-
seroprevalence to be 4.8% (95% CI 2.4–8.0%; n = 341) in the first oRegistro=80560310056) that combines SARS-CoV-2 antigen-
week, 8.5% (95% CI 5.9–11.4%; n = 469) in the second week, 10.9% coated particles to qualitatively detect IgG and IgM antibodies.
(95% CI 7.9–14.4%; n = 577) in the third week, 6.6% (95% CI 4.3–9.4%; Overall, the seroprevalence without any adjustment was 4.0% (95%
n = 604) in the fourth week, and 10.8% (95% CI 8.2–13.9%; n = 775) CI 3.3–4.7%), and the weighted prevalence was 3.8% (95% CI 3.1–
in the fifth week (Stringhini et al., 2020). 4.5%). Lower estimates were found following adjustment for test
In Denmark, a total of 20,640 blood donations were given by 17– sensitivity and specificity, at 3.6% (95% CI 2.7–4.4%) for the non-
69-year-old donors from April 6 to May 3, 2020, which were then weighted prevalence and 3.3% (95% CI 2.6–4.1%) for the weighted
subjected to a plasma or whole blood lateral flow test, performed prevalence (Amorim Filho et al., 2020).
according to the manufacturer’s recommendations (IgM/IgG In the USA, SARS-CoV-2-specific antibody testing using a lateral
Antibody to SARS-CoV-2 lateral flow test; Livzon Diagnostics flow immunoassay test (Premier Biotech) was performed on the
Inc., Zhuhai, Guangdong, China) (Erikstrup et al., 2020). The overall residents of Los Angeles County, California, or within a 15-mile (24-
unadjusted seroprevalence was 2.0% (95% CI 1.8–2.2%), and after km) radius, between April 10 and April 14, 2020. Overall, 35 of the
adjusting for assay sensitivity and specificity (including their CI), 863 adults included tested positive, with an unadjusted prevalence
the overall seroprevalence was 1.9% (95% CI 0.8–2.3%) (Erikstrup of 4.06% (exact binomial CI 2.84–5.60%). After adjusting for test
et al., 2020). sensitivity and specificity, the unweighted and weighted preva-
In Italy, 390 blood donors in the Lodi Red Zone were recruited lence rates of SARS-CoV-2 antibodies were 4.34% (bootstrap CI
from March 18 to April 6, 2020, for a study that utilized the SARS- 2.76–6.07%) and 4.65% (bootstrap CI 2.52–7.07%), respectively
CoV-2 microneutralization assay (Percivalle et al., 2020). A total of (Sood et al., 2020).
91 (23%) participants were positive for SARS-CoV-2-specific In the San Francisco Bay Area, the seroprevalence was tested
neutralizing antibodies (1:10), while 299 (77%) tested negative using the Architect SARS166 CoV-2 anti-nucleocapsid protein IgG
(<1:10). In contrast, the seroprevalence was only 0.99% (n = 9) and was found to be only 0.1% in 1000 blood donors in March 2020
among 904 healthy blood donors in the Apulia region, South (Ng et al., 2020).
Eastern Italy (Fiore et al., 2020). Recently, one large series including In New York, a total of 15,626 adult residents with complete
3609 adult volunteers from five administrative departments of the data were tested from April 19 to April 28, 2020. Of the included
Liguria and Lombardia regions showed the seroprevalence was residents, 15,101 (96.6%) had suitable specimens, of which 1887
11.0% (n = 389) (Vena et al., 2020). (12.5%) were reactive and 340 (2.3%) were indeterminate. After

315
C.-C. Lai, J.-H. Wang and P.-R. Hsueh
Table 1
Summary of population-based studies.

Author Study site Test Period Study subjects Seroprevalence Incidence (per 1,000,000 population) in
(all 2020) indicated country (as of September 9,
2020) (World Health Organization
(WHO), 2020)
Europe
Pollán et al. Spain (national and Point-of-care antibody test, April 27–May 11 35 883 households 5.0% (95% CI 4.7–5.4%) by the point-of-care test 10 672.5
(2020) regional level) chemiluminescent microparticle and 4.6% (95% CI 4.3–5.0%) by immunoassay
immunoassay for IgG
Stringhini et al. Geneva, Switzerland Anti-SARS-CoV-2-IgG antibodies using a April 6–May 9 2766 participants from 4.8% (95% CI 2.4–8.0%), 8.5% (95% CI 5.9–11.4%), 5066.5
(2020) commercially available ELISA 1339 households 10.9% (95% CI 7.9–14.4%), 6.6% (95% CI 4.3–9.4%),
and 10.8% (95% CI 8.2–13.9%) in weeks 1, 2, 3, 4,
and 5, respectively
Erikstrup et al. Denmark Commercial lateral flow test for IgG/IgM April 6– May 3 20 640 blood donors aged 1.9% (95% CI 0.8–2.3%) 3029.4
(2020) 17–69 years
Percivalle et al. Lodi Red Zone in NA April 6 390 blood donors 23% (n = 91) 4570.5
(2020) Lombardy, Italy
Fiore et al. Apulia region, South Anti-SARS-CoV-2 IgG and IgM May 1–31 904 healthy blood donors 0.99% (n = 9)
(2020) Eastern Italy
Vena et al. 5 administrative Anti-SARS-CoV-2 IgM or IgG March 1–April 30 3609 adults volunteers 11.0% (n = 398)
(2020) departments of the
Liguria and
Lombardia regions in
Italy
Gallian et al. France Antibodies neutralizing SARS-CoV-2 The last week of 998 blood donors 2.7% (n = 27) 4603.9
(2020) March, or the first
week of April
Carrat et al. Ile-de-France (IDF), Anti-SARS-CoV-2 ELISA IgG against spike May 4–June 23 14 628 adults Overall, 6.7% (n = 983)
316

(2020) Grand Est (GE), and (ELISA-S) and nucleocapsid (ELISA-NP), Adjusted estimates
Nouvelle Aquitaine and anti-SARS-CoV-2 neutralizing ELISA-S: IDF 10%, GE 9.0%, NA 3.1%
(NA) in France antibody titers 40 (SN) ELISA-NP: IDF 5.7%, GE 6.0%, NA 0.6%
SN: IDF 5.0%, GE 4.3%, NA,
1.3%
Bogogiannidou Greece Abbott SARS-CoV-2 IgG assay March and April 6586 samples 0.36% (n = 24) 1092.4
et al. (2020)

America

International Journal of Infectious Diseases 101 (2020) 314–322


Havers et al. 10 regions in USA SARS-CoV-2 spike protein ELISA March 23–May 12 16 025 residents 1.0–6.9% 18 562.2
(2020)
Sood et al. Los Angeles County, Lateral flow immunoassay test (Premier April 10–14 1952 adult residents 4.06% (n = 35)
(2020) California Biotech)
Rosenberg et al. New York SARS-CoV-2 IgG testing was conducted April 19–28 15 101 adult residents 12.5% (n = 1887)
(2020) using a microsphere immunoassay
Nir et al. (2020) Indiana Chemiluminescent microparticle April 25–29 3658 randomly selected 1.01% (n = 38)
immunoassay for SARS-CoV-2 IgG persons
Sutton et al. Oregon SARS-CoV-2 IgG May 11–June 15 897 participants 1.0% (n = 9)
(2020)
McLaughlin Blaine County Abbott Architect SARS-CoV-2 IgG May 4–19 917 adult residents 22.7% (n = 208)
et al. (2020) chemiluminescent microparticle
immunoassay
Naranbhai et al. Chelsea BioMedomics SARS-CoV-2 combined April 14–15 200 asymptomatic 31.5% (n = 63)
(2020) IgM/IgG LFA (BioMedomics, Morrisville, residents
NC)
Ng et al. (2020) Two San Francisco Bay Abbott Architect SARS-CoV-2 IgG (FDA, March 387 hospitalized patients 0.26% of 387 hospitalized patients admitted for 19 255.0
Area populations in USA) and IgM (prototype) assays admitted for non- non-respiratory indications and 0.1% in 1000
the USA respiratory indications blood donors
and 1000 blood donors
C.-C. Lai, J.-H. Wang and P.-R. Hsueh International Journal of Infectious Diseases 101 (2020) 314–322

weighting, 12.5% were estimated to be reactive, and after further


adjustment for test characteristics, the estimated cumulative
incidence was 14.0% (95% CI 13.3–14.7%) (Rosenberg et al., 2020).
The largest study (Havers et al., 2020) was conducted in several
regions, including San Francisco Bay Area, California, Connecticut,
South Florida, Louisiana, Minneapolis-St Paul (St Cloud metro
area), Minnesota, Missouri, New York, Philadelphia metro area,
Pennsylvania, Utah, and Western Washington State from March 23
to May 12, 2020. A validated SARS-CoV-2 spike protein ELISA
(all 2020)

(Freeman et al., 2020) was used to test 16,025 persons, and the
Period

1351.4

290.2

413.1
62.9

results showed that the adjusted estimates of seroprevalence


ranged from 1.0% in the San Francisco Bay Area (collected April 23–
0.408%) for April 11–13, April 25–27, and May 9–

327 in main wave and 261 0.6% (n = 2) in main wave; 0.4% (n = 1) in post-
27, 2020) to 6.9% in persons in New York City (collected March 23–
0.048% (95% CI 0.006–0.174%), 0.135% (95% CI

April 1, 2020) (Havers et al., 2020).


0.049–0.293%), and 0.222% (95% CI 0.107–

In Indiana, the seroprevalence among 3658 randomly selected


non-institutional participants was 1.01% (n = 38) between April 25
and April 29, 2020 (Nir et al., 2020). In Oregon, the overall
seropositivity was 1.0% (n = 9) among 897 participants from 19
facilities participating in the Influenza-like Illness Surveillance
Network (Sutton et al., 2020). In Blaine County, 208 out of 917 adult
4.0% (95% CI 3.3–4.7%)

residents had positive anti-SARS-CoV-2 IgG and the overall


seroprevalence was 22.7% between May 4 and May 9 (McLaughlin
11, respectively

15.6% (n = 24)

0.07% (n = 1)

et al., 2020). The highest seroprevalence was found to be 31.5%


21.4–37.7%

among 200 asymptomatic residents in Chelsea, Massachusetts


3.2–3.8%

(Naranbhai et al., 2020).


wave
Test

Asia
of two university hospitals
380 healthy blood donors

samples from outpatients


154 young policeman

In China, a serological survey (Xu et al., 2020) was conducted in


1500 residual serum
Household surveys

2857 blood donors

seven cities, including Hubei Province (Wuhan, Honghu, and


17 368 residents

Jingzhou), Guangdong Province (Guangzhou and Foshan), Sichuan


in post-wave

Province (Chengdu), and Chongqing between March 9 and April 10,


Study site

2020, and a validated serological test (Liu et al., 2020) for the
presence of antibodies (IgM or IgG) against SARS-CoV-2 was tested
in a total of 17 368 individuals. For 10,499 individuals in the
CI, confidence interval; NA, not applicable; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
14) and post-wave
March 9– April 10

community setting, the seropositivity ranged from 0.6% among


(January 29–April

(April 15–June 6)
Wondfo lateral flow point-of-care test for April 11– May 11

9442 community residents in Chengdu, Sichuan, and 1.4% among


April 14–27

May 25–29
May 20–30

factory workers in Guangzhou, Guangdong, to 3.2% among 219


Main wave
June–July

relatives of healthcare workers (HCWs), and 3.8% among 346 hotel


Author

staff members in Wuhan, Hubei (Xu et al., 2020). Moreover,


seropositivity decreased progressively in other cities as the
distance to the epicenter increased (Xu et al., 2020).
In-house indirect ELISA detecting IgG to

Elecsys Anti-SARS-CoV-2 (Roche, Solna,


SARS-CoV-2 receptor binding domain
method on Architect Ci8200 (Abbott)

In Pakistan, 24 (15.6%) of 154 asymptomatic young policemen in


Chemiluminescence immunoassay

high-risk areas of Lahore had positive anti-SARS-CoV-2 IgG


(Chughtai et al., 2020), as did 21.4–37.7% of 380 healthy blood
Electro-chemiluminescence

donors in Karachi (Younas et al., 2020).


In Malaysia, the seropositivity of anti-SARS-CoV-2 IgG was 0.6%
(2/327) and 0.4% (1/261) based on serum samples collected for
non-respiratory and respiratory infections during the pandemic
immunoassay

and post-pandemic periods, respectively (Sam et al., 2020).


Switzerland)

In Seoul, Korea, the seroprevalence was only 0.07% based on the


IgG/IgM

IgM/IgG

surveillance of 1500 residual samples from outpatients of two


university hospitals (Noh et al., 2020).
NA
Rio de Janeiro, Brazil

Southwestern Seoul,

Summary
Rio Grande do Sul,

Kuala Lumpur and


Selangor, Malaysia
Karachi, Pakistan
Wuhan, China

In summary, the reported seroprevalence ranged from <0.1% to


more than 20% in the different regions and could increase with
Pakistan

time (Table 1). Regular monitoring of the seroprevalence at each


Korea
Brazil

site should be indicated to establish the epidemiology of COVID-19.


Xu et al. (2020)
Chughtai et al.
et al. (2020)
Amorim Filho

Healthcare workers (HCWs)


Silveira et al.

Younas et al.

Sam et al.

Noh et al.
(2020)

(2020)

(2020)

(2020)

Nosocomial transmission of SARS-CoV-2 is common within


(2020)

Asia

hospitals, and COVID-19 is a threat for HCWs, especially those


without appropriate personal protective equipment (PPE)

317
C.-C. Lai, J.-H. Wang and P.-R. Hsueh International Journal of Infectious Diseases 101 (2020) 314–322

(Houlihan et al., 2020; Hunter et al., 2020a, b; Kluytmans-van den confirmed COVID-19 cases showed higher antibody positivity
Bergh et al., 2020; Lai et al., 2020f; Keeley et al., 2020; Wei et al., than those without exposure (81/593 (13.7%) vs 116/2435 (4.8%)),
2020). One population-based study demonstrated that the positive with an odds ratio (OR) of 3.15 (95% CI 2.33–4.25). Moreover, prior
rate of anti-SARS-CoV-2 IgG or IgM in the hospital setting was 2.5% anosmia was associated with the presence of antibodies, with an
(170/6919), which was higher than that reported in the community OR of 7.78 (95% CI 5.22–11.53), as well as fever and cough
setting (0.8%, 81/10,449) (Xu et al., 2020). In that study (Xu et al., (Steensels et al., 2020).
2020), the positive rate was highest for HCWs in Wuhan, Hubei Another study in Belgium performed by Martin et al. (2020)
(3.8%, 27/714). reported on 326 staff from COVID-19 highly exposed units who
Many studies had evaluated the seroprevalence among HCWs received two rounds of serological testing (Euroimmun Anti-SARS-
(Steensels et al., 2020; Martin et al., 2020; Korth et al., 2020; CoV-2 IgG; Medizinische Labordiagnostika AG, Lübeck, Germany).
Stubblefield et al., 2020; Chen et al., 2020a, b; Pallett et al., 2020; The IgG seroprevalence among those patients without a positive
Grant et al., 2020; Hunter et al., 2020a, b; Self et al., 2020; Moscola SARS-CoV-2 RT-PCR at baseline was 8.3% (n = 27) on day 1 and 9.5%
et al., 2020; Plebani et al., 2020). In Belgium, active screening was (n = 31) on day 15 (Martin et al., 2020).
performed using a single-lane rapid IgG/IgM lateral flow assay In Germany, 316 HCWs who had been in direct contact with
directed to the nucleocapsid protein of SARS-CoV-2 (COVID-19 COVID-19 patients underwent semi-quantitative ELISA testing
IgG/IgM Rapid Test Cassette; Multi-G), for 3056 staff in a tertiary (Euroimmun Medizinische Labordiagnostika, Lübeck, Germany) in
center from April 22 to April 30, 2020 (Steensels et al., 2020). a survey conducted from March 25 to April 21, 2020, and the
Overall, 197 staff (6.4%, 95% CI 5.5–7.3%) had IgG antibodies for seroprevalence was found to be 1.6% (n = 5) (Korth et al., 2020).
SARS-CoV-2. In addition, household contacts of suspected or Moreover, the seroprevalence was numerically higher in the

Table 2
Summary of the studies on healthcare workers (HCWs), children, and pregnant women.

Author Study site Test Period (all 2020) Study subjects Seroprevalence rate
Healthcare workers (HCWs)
Steensels A tertiary center in A single-lane rapid IgG/IgM lateral flow assay directed April 22–30 3056 staff 6.4% (n = 197)
et al. Belgium to the nucleocapsid protein of SARS-CoV-2 (COVID-19
(2020) IgG/IgM Rapid Test Cassette; Multi-G)
Martin et al. A tertiary referral Euroimmun anti-SARS-CoV-2 IgG Medizinische April 15–May 18 326 staff members working 8.3% (n = 27) and 9.5%
(2020) hospital in Belgium Labordiagnostika AG, Lübeck, Germany in COVID-19 highly exposed (n = 31) on days 1 and
units 15, respectively
Korth et al. Germany SARS-CoV-2-IgG March 25–April 316 HCWs 1.6% (n = 5)
(2020) 21
Stubblefield Nashville, Tennessee A validated ELISA against the extracellular domain of April 3–13 249 HCWs who worked in 7.6% (n = 19)
et al. the SARS-CoV-2 spike protein hospital units with COVID-
(2020) 19 patients for 1 month
Chen et al. A hospital in China Enzyme immunoassay and microneutralization assay NA 105 HCWs exposed to 4 17.1% (n = 18)
(2020) patients
Pallett et al. Multicenter in UK EDI novel coronavirus COVID-19 IgG ELISA kit (Epitope April 8–June 12 1299 symptomatic and 405 10.6% in asymptomatic
(2020) Diagnostics, San Diego, CA, USA) asymptomatic HCWs HCWs and 44.7% in
symptomatic HCWs
Grant et al. An acute integrated Elecsys Anti-SARS-CoV-2 assay (Roche Diagnostics, May 15–June 5 2004 HCWs 31.6%
(2020) care organization in Basel, Switzerland) for IgG and IgM
London, UK
Hunter et al. An integrated Abbott Architect i2000SR chemiluminescent April 29–May 8 734 HCWs 1.6% (n = 12)
(2020) healthcare system microparticle immunoassay for anti-SARS-CoV-2 IgG
with 17 hospital in
Indiana
Moscola 52 sites in New York Seven different assays for anti-SARS-CoV-2 IgG April 20–June 23 40 329 HCWs 13.7% (n = 5523)
et al. City
(2020)
Self et al. 13 medical centers in Enzyme-linked immunosorbent assay against the April 13–June 19 3248 HCWs 6.0 (%) (n = 194)
(2020) the United States extracellular domain of the SARS-CoV-2 spike protein
Plebani et al. Main hospitals of the Maglumi 2000 Plus (New Industries Biomedical February 22– 8285 HCWs 4.6% (n = 378)
(2020) Veneto Region of Italy Engineering Co., Ltd (Snibe), Shenzhen, China) May 29

Children
Torres et al. A large school The novel coronavirus (2019-nCoV) IgG/IgM Test Kit May 4–19 (8–10 1009 students 9.9% (95% CI 8.2–11.8%)
(2020) community in (Colloidal Gold) from Genrui Biotech Inc., China weeks after a
Santiago, Chile school outbreak)
Dingens Seattle Children’s Abbott SARS-CoV-2 IgG chemiluminescent March and April 1775 samples collected from 1% (n = 10)
et al. Hospital microparticle immunoassay 1076 children
(2020)

Pregnant women
Flannery Two centers in ELISA for SARS-CoV-2 IgG and IgM antibodies April 4–June 3 1293 parturient women 6.2% (n = 80)
et al. Philadelphia
(2020)
Crovetto Three university VIRCLIA (Vircell Microbiologist, Granada, Spain) for April 14–May 5 372 women at 10–16 weeks 14% (n = 125)
et al. hospitals in anti-SARS-CoV-2 IgG, IgM, and IgA antibodies of gestation and 502 during
(2020) Barcelona, Spain delivery

CI, confidence interval; COVID-19, coronavirus disease 2019; NA, not applicable; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

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intermediate-risk group than in the high-risk group (2/37 (5.4%) vs (OR 1.20, 95% CI 0.82–1.76) (Amorim Filho et al., 2020). A similar
3/244 (1.2%), p = 0.13) (Korth et al., 2020). trend was observed in a French study, in which the seroprevalence
At Vanderbilt University Medical Center in Tennessee, 249 was higher in males than in females, but it did not differ
HCWs were investigated. These HCWs had regularly had direct significantly (2.82% vs 2.69%) (Gallian et al., 2020).
contact with units housing adult COVID-19 patients in the month However, in Spain, the seroprevalence among males and
prior to undergoing testing with a validated ELISA against the females was similar, as assessed by the point-of-care test (5.0%,
extracellular domain of the SARS-CoV-2 spike protein (Stubblefield 95% CI 4.7–5.5% vs 5.0%, 95% CI 4.6–5.4%) and immunoassay (4.6%,
et al., 2020). Overall, 19 (7.6%) of the healthcare personnel tested 95% CI 4.2–5.0% vs 4.6%, 95% CI 4.2–5.0%) (Pollán et al., 2020). In the
positive for SARS-CoV-2 antibodies, and seropositivity was more USA, there was no clear association between seroprevalence and
common among those who reported not generally wearing PPE for sex across sites (Havers et al., 2020).
all encounters when compared to those who reported always Overall, these findings indicate that the seroprevalence does
wearing PPE (15.8% vs 4.3%, p = 0.07) (Stubblefield et al., 2020). not differ significantly between males and females.
In China, 105 HCWs exposed to four laboratory-confirmed
COVID-19 patients received testing with an enzyme immunoassay Children
(EIA), as well as a microneutralization assay, to assess the
seroprevalence on day 14 of quarantine, in which 17.14% (n = 18) Four population-based studies have demonstrated a lower
of HCWs were seropositive (Chen et al., 2020a, b). A higher risk of seroprevalence in children (Pollán et al., 2020; Stringhini et al.,
seroconversion was found for doctors exposed to COVID-19 2020; Havers et al., 2020; Sutton et al., 2020). Compared to subjects
patients (OR 346.837, 95% CI 8.924–13479.434), while a lower aged 20–49 years, children aged 5–9 years had a significantly lower
risk of seroconversion was closely related to direct contact with seroprevalence of 0.8% (1/123) (relative risk 0.32, 95% CI 0.13–0.63)
COVID-19 patients wearing face masks (OR 0.127, 95% CI 0.017– in a Swiss surveillance study (SEROCoV-POP) (Stringhini et al.,
0.968) (Chen et al., 2020a, b). 2020). In Spain, the ENE-COVID study showed that the seropreva-
Based on the above findings (Table 2), HCWs are at high risk of lence rates in subjects aged 0–19 years were 3.4% using the point-
acquiring SARS-CoV-2 infection, and adequate PPE could help of-care test and 3.8% by immunoassay, which were lower than the
protect them from COVID-19. rates reported for any other age group (4.4–6.0% using the point-of-
In the UK, a multicenter investigation showed that the care test and 4.5–5.0% by immunoassay) (Pollán et al., 2020). In the
seroprevalence was 10.6% among 405 asymptomatic HCWs and USA, the seroprevalence in subjects aged 0–18 years ranged from
44.7% among 1299 symptomatic HCWs (Pallett et al., 2020). In 0.7% (95% CI 0–2.5%) in Western Washington State to 5.8% (95% CI
another investigation in the UK, an overall seropositivity rate of 0–14.3%) in Minneapolis-St Paul-St Cloud metro area (Minnesota)
31.6% among HCWs was found, which was highest among staff (Havers et al., 2020). Moreover, the seroprevalence in this age
working in a clinical environment with direct patient contact group was numerically lower than that in other age groups in
(34.7%) and lowest among those working in non-clinical environ- Western Washington State, New York, Louisiana, Missouri, and
ments without patient contact (22.6%) (Grant et al., 2020). Connecticut (Havers et al., 2020).
In contrast, a study in the USA showed that employees with In addition, a cross-sectional study using the novel coronavirus
heavy COVID-19 exposure had antibody prevalence similar to (2019-nCoV) IgG/IgM Test Kit (Colloidal Gold; Genrui Biotech Inc.,
those with limited or no exposure and suggested that PPE use China) was conducted 8–10 weeks after a school outbreak, and the
seems effective in the prevention of COVID-19 infection in HCWs results showed antibody positivity rates of 9.9% (95% CI 8.2–11.8%)
(Hunter et al., 2020a, b). Another study showed similar findings, i.e. for 1009 students (Table 2). Moreover, the positivity was associated
that seroprevalence was lower among personnel who reported with a younger age (p = 0.01), lower grade (p = 0.05), prior RT-PCR
always wearing a face covering while caring for patients (6%), positivity (p = 0.03), and history of contact with a confirmed case (p
compared with those who did not (9%) (Self et al., 2020). In the < 0.001) (Torres et al., 2020). In another study (Dingens et al.,
largest cohort study enrolling 40,329 HCWs in New York City, the 2020), the seroprevalence in children who had visited Seattle
overall seroprevalence was 13.7% (n = 5523); however, only 9.0% (n Children’s Hospital during the initial Seattle outbreak was
= 3077) among 34 251 without PCR testing were seropositive determined using the Abbott SARS-CoV-2 IgG chemiluminescent
(Moscola et al., 2020). microparticle immunoassay, and only eight children were found to
be seropositive, with a seroprevalence of 0.7% (Table 2).
Male and female population Overall, children seem to have a lower seroprevalence than
adults, which is consistent with previous epidemiological findings
Several population-based studies have demonstrated differ- of laboratory-confirmed COVID-19 cases (Lee et al., 2020a, b; Wang
ences in seroprevalence rates among male and female subjects et al., 2020; Huang et al., 2020; Li et al., 2020a, b).
(Pollán et al., 2020; Stringhini et al., 2020; Amorim Filho et al.,
2020; Sood et al., 2020; Rosenberg et al., 2020). Other populations
In New York, the weighted seroprevalence rate in males was
14.8% (95% CI 13.8–15.8%), which was numerically higher than that Pregnant women can be infected by SARS-CoV-2, although data
in females (13.3%, 95% CI 12.4–14.2%) (Rosenberg et al., 2020). In in this population are limited (Ashraf et al., 2020; Barbero et al.,
Switzerland, the rate of positive SARS-CoV-2 serology tests among 2020; Sahin et al., 2020; Chen et al., 2020a, b; Schmid et al., 2020;
males was 9.0% (118/1312), which was higher than that among Yu et al., 2020). Recently, 1293 parturient women were tested for
females, at 6.9% (101/1454) (Erikstrup et al., 2020). In Los Angeles, SARS-CoV-2 IgG and IgM antibodies to the spike receptor-binding
the unweighted portion of the population positive for IgM or IgG domain antigen using an ELISA at two centers in Philadelphia from
among males was 5.18% (95% CI 3.10–8.07%), which was April 4 to June 3, 2020. The results demonstrated that 80/1293
numerically higher than that among females (3.31%, 95% CI (6.2%) parturient women possessed IgG and/or IgM SARS-CoV-2-
1.94–5.24%) (Sood et al., 2020). In Brazil, males had a higher specific antibodies (Table 2) (Flannery et al., 2020). Another study
seroprevalence, after adjustment, than females (4.1% vs 3.5%, at three university hospitals in Spain showed that 54/372 (15%)
respectively), but the difference was not statistically significant women in the first trimester of pregnancy and 71/502 (14%)

319
C.-C. Lai, J.-H. Wang and P.-R. Hsueh International Journal of Infectious Diseases 101 (2020) 314–322

women in the third trimester had anti-SARS-CoV-2 IgG, IgM, or IgA Ethical approval
using the VIRCLIA test (Vircell Microbiologist, Granada, Spain)
(Crovetto et al., 2020). No ethical approval sought.
A previous study of 187 COVID-19 patients showed that the risk
of COVID-19 was higher for patients with blood group A than for Conflict of interest
those with a blood group other than A (OR 1.544, 95% CI 1.122–
2.104; p = 0.006), while patients with blood group O had a lower We declare no conflict of interest.
risk of COVID-19 than patients with non-O blood groups (OR 0.649,
95% CI 0.457–0.927; p = 0.018) (Wu et al., 2020). Furthermore, References
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