Abstract

Introduction

Even though severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) only emerged at the end of 2019, the associated disease–coronavirus disease 2019 (COVID-19)–has spread rapidly to more than 180 countries/regions worldwide and has consequently led to a global pandemic (World Health Organization (WHO), 2020). As of September 7, 2020, nearly 27 million COVID-19 cases have been reported worldwide, causing 876,616 deaths, with an associated case fatality rate of 3.3% (World Health Organization (WHO), 2020, Lai et al., 2020a, Lai et al., 2020b, Sheng et al., 2020).

Currently, the diagnosis of COVID-19 is confirmed by the detection of SARS-CoV-2 via real-time reverse transcription polymerase chain reaction (qRT-PCR) assays that target open reading frame-1 antibodies, envelope proteins, nucleocapsid proteins, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 target genes, among suspected cases with an exposure history and signs/symptoms of SARS-CoV-2 infection (Lai et al., 2020c). However, the clinical manifestations of COVID-19 include both respiratory and extra-respiratory signs and symptoms and can range from an asymptomatic mild disease to severe disease/acute respiratory tract infections (Lai et al., 2020d, Lai et al., 2020e, Li et al., 2020a, Li et al., 2020b). Therefore, misdiagnosis of COVID-19 can occur in patients without a characteristic presentation, even for asymptomatic and mild infections, and in places where qRT-PCR is unavailable. These issues could limit our understanding of the extent of SARS-CoV-2 infection and further affect the implementation of infection control and prevention policies.

To resolve this issue, the use of a serological test to detect anti-SARS-CoV-2 antibodies could be a better way to estimate the 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). Hence, this review was conducted to provide updated and comprehensive information about the seroprevalence of the SARS-CoV-2 antibody in different populations.

Population-based seroprevalence studies

Healthcare workers (HCWs)

Nosocomial transmission of SARS-CoV-2 is common within hospitals, and COVID-19 is a threat for HCWs, especially those without appropriate personal protective equipment (PPE) (Houlihan et al., 2020, Hunter et al., 2020a, Hunter et al., 2020b, Kluytmans-van den Bergh et al., 2020, Lai et al., 2020f, Keeley et al., 2020, Wei et al., 2020). One population-based study demonstrated that the positive rate of anti-SARS-CoV-2 IgG or IgM in the hospital setting was 2.5% (170/6919), which was higher than that reported in the community setting (0.8%, 81/10,449) (Xu et al., 2020). In that study (Xu et al., 2020), the positive rate was highest for HCWs in Wuhan, Hubei (3.8%, 27/714).

Many studies had evaluated the seroprevalence among HCWs (Steensels et al., 2020, Martin et al., 2020, Korth et al., 2020, Stubblefield et al., 2020, Chen et al., 2020a, Chen et al., 2020b, Pallett et al., 2020, Grant et al., 2020, Hunter et al., 2020a, Hunter et al., 2020b, Self et al., 2020, Moscola et al., 2020, Plebani et al., 2020). In Belgium, active screening was performed using a single-lane rapid IgG/IgM lateral flow assay directed to the nucleocapsid protein of SARS-CoV-2 (COVID-19 IgG/IgM Rapid Test Cassette; Multi-G), for 3056 staff in a tertiary center from April 22 to April 30, 2020 (Steensels et al., 2020). Overall, 197 staff (6.4%, 95% CI 5.5–7.3%) had IgG antibodies for SARS-CoV-2. In addition, household contacts of suspected or confirmed COVID-19 cases showed higher antibody positivity than those without exposure (81/593 (13.7%) vs 116/2435 (4.8%)), with an odds ratio (OR) of 3.15 (95% CI 2.33–4.25). Moreover, prior anosmia was associated with the presence of antibodies, with an OR of 7.78 (95% CI 5.22–11.53), as well as fever and cough (Steensels et al., 2020).

Another study in Belgium performed by Martin et al. (2020) reported on 326 staff from COVID-19 highly exposed units who received two rounds of serological testing (Euroimmun Anti-SARS-CoV-2 IgG; Medizinische Labordiagnostika AG, Lübeck, Germany). The IgG seroprevalence among those patients without a positive SARS-CoV-2 RT-PCR at baseline was 8.3% (n = 27) on day 1 and 9.5% (n = 31) on day 15 (Martin et al., 2020).

In Germany, 316 HCWs who had been in direct contact with COVID-19 patients underwent semi-quantitative ELISA testing (Euroimmun Medizinische Labordiagnostika, Lübeck, Germany) in a survey conducted from March 25 to April 21, 2020, and the seroprevalence was found to be 1.6% (n = 5) (Korth et al., 2020). Moreover, the seroprevalence was numerically higher in the intermediate-risk group than in the high-risk group (2/37 (5.4%) vs 3/244 (1.2%), p = 0.13) (Korth et al., 2020).

At Vanderbilt University Medical Center in Tennessee, 249 HCWs were investigated. These HCWs had regularly had direct contact with units housing adult COVID-19 patients in the month prior to undergoing testing with a validated ELISA against the extracellular domain of the SARS-CoV-2 spike protein (Stubblefield et al., 2020). Overall, 19 (7.6%) of the healthcare personnel tested positive for SARS-CoV-2 antibodies, and seropositivity was more common among those who reported not generally wearing PPE for all encounters when compared to those who reported always wearing PPE (15.8% vs 4.3%, p = 0.07) (Stubblefield et al., 2020).

In China, 105 HCWs exposed to four laboratory-confirmed COVID-19 patients received testing with an enzyme immunoassay (EIA), as well as a microneutralization assay, to assess the seroprevalence on day 14 of quarantine, in which 17.14% (n = 18) of HCWs were seropositive (Chen et al., 2020a, Chen et al., 2020b). A higher risk of seroconversion was found for doctors exposed to COVID-19 patients (OR 346.837, 95% CI 8.924–13479.434), while a lower risk of seroconversion was closely related to direct contact with COVID-19 patients wearing face masks (OR 0.127, 95% CI 0.017–0.968) (Chen et al., 2020a, Chen et al., 2020b).

Based on the above findings (Table 2 ), HCWs are at high risk of acquiring SARS-CoV-2 infection, and adequate PPE could help protect them from COVID-19.

In the UK, a multicenter investigation showed that the seroprevalence was 10.6% among 405 asymptomatic HCWs and 44.7% among 1299 symptomatic HCWs (Pallett et al., 2020). In another investigation in the UK, an overall seropositivity rate of 31.6% among HCWs was found, which was highest among staff working in a clinical environment with direct patient contact (34.7%) and lowest among those working in non-clinical environments without patient contact (22.6%) (Grant et al., 2020).

In contrast, a study in the USA showed that employees with heavy COVID-19 exposure had antibody prevalence similar to those with limited or no exposure and suggested that PPE use seems effective in the prevention of COVID-19 infection in HCWs (Hunter et al., 2020a, Hunter et al., 2020b). Another study showed similar findings, i.e. that seroprevalence was lower among personnel who reported always wearing a face covering while caring for patients (6%), compared with those who did not (9%) (Self et al., 2020). In the largest cohort study enrolling 40,329 HCWs in New York City, the overall seroprevalence was 13.7% (n = 5523); however, only 9.0% (n = 3077) among 34 251 without PCR testing were seropositive (Moscola et al., 2020).

Male and female population

Several population-based studies have demonstrated differences in seroprevalence rates among male and female subjects (Pollán et al., 2020, Stringhini et al., 2020, Amorim Filho et al., 2020, Sood et al., 2020, Rosenberg et al., 2020).

In New York, the weighted seroprevalence rate in males was 14.8% (95% CI 13.8–15.8%), which was numerically higher than that in females (13.3%, 95% CI 12.4–14.2%) (Rosenberg et al., 2020). In Switzerland, the rate of positive SARS-CoV-2 serology tests among males was 9.0% (118/1312), which was higher than that among females, at 6.9% (101/1454) (Erikstrup et al., 2020). In Los Angeles, the unweighted portion of the population positive for IgM or IgG among males was 5.18% (95% CI 3.10–8.07%), which was numerically higher than that among females (3.31%, 95% CI 1.94–5.24%) (Sood et al., 2020). In Brazil, males had a higher seroprevalence, after adjustment, than females (4.1% vs 3.5%, respectively), but the difference was not statistically significant (OR 1.20, 95% CI 0.82–1.76) (Amorim Filho et al., 2020). A similar trend was observed in a French study, in which the seroprevalence was higher in males than in females, but it did not differ significantly (2.82% vs 2.69%) (Gallian et al., 2020).

However, in Spain, the seroprevalence among males and females was similar, as assessed by the point-of-care test (5.0%, 95% CI 4.7–5.5% vs 5.0%, 95% CI 4.6–5.4%) and immunoassay (4.6%, 95% CI 4.2–5.0% vs 4.6%, 95% CI 4.2–5.0%) (Pollán et al., 2020). In the USA, there was no clear association between seroprevalence and sex across sites (Havers et al., 2020).

Overall, these findings indicate that the seroprevalence does not differ significantly between males and females.

Children

Four population-based studies have demonstrated a lower seroprevalence in children (Pollán et al., 2020, Stringhini et al., 2020, Havers et al., 2020, Sutton et al., 2020). Compared to subjects aged 20–49 years, children aged 5–9 years had a significantly lower seroprevalence of 0.8% (1/123) (relative risk 0.32, 95% CI 0.13–0.63) in a Swiss surveillance study (SEROCoV-POP) (Stringhini et al., 2020). In Spain, the ENE-COVID study showed that the seroprevalence rates in subjects aged 0–19 years were 3.4% using the point-of-care test and 3.8% by immunoassay, which were lower than the rates reported for any other age group (4.4–6.0% using the point-of-care test and 4.5–5.0% by immunoassay) (Pollán et al., 2020). In the USA, the seroprevalence in subjects aged 0–18 years ranged from 0.7% (95% CI 0–2.5%) in Western Washington State to 5.8% (95% CI 0–14.3%) in Minneapolis-St Paul-St Cloud metro area (Minnesota) (Havers et al., 2020). Moreover, the seroprevalence in this age group was numerically lower than that in other age groups in Western Washington State, New York, Louisiana, Missouri, and Connecticut (Havers et al., 2020).

In addition, a cross-sectional study using the novel coronavirus (2019-nCoV) IgG/IgM Test Kit (Colloidal Gold; Genrui Biotech Inc., China) was conducted 8–10 weeks after a school outbreak, and the results showed antibody positivity rates of 9.9% (95% CI 8.2–11.8%) for 1009 students (Table 2). Moreover, the positivity was associated with a younger age (p = 0.01), lower grade (p = 0.05), prior RT-PCR positivity (p = 0.03), and history of contact with a confirmed case (p < 0.001) (Torres et al., 2020). In another study (Dingens et al., 2020), the seroprevalence in children who had visited Seattle Children’s Hospital during the initial Seattle outbreak was determined using the Abbott SARS-CoV-2 IgG chemiluminescent microparticle immunoassay, and only eight children were found to be seropositive, with a seroprevalence of 0.7% (Table 2).

Overall, children seem to have a lower seroprevalence than adults, which is consistent with previous epidemiological findings of laboratory-confirmed COVID-19 cases (Lee et al., 2020a, Lee et al., 2020b, Wang et al., 2020, Huang et al., 2020, Li et al., 2020a, Li et al., 2020b).

Other populations

Pregnant women can be infected by SARS-CoV-2, although data in this population are limited (Ashraf et al., 2020, Barbero et al., 2020, Sahin et al., 2020, Chen et al., 2020a, Chen et al., 2020b, Schmid et al., 2020, Yu et al., 2020). Recently, 1293 parturient women were tested for SARS-CoV-2 IgG and IgM antibodies to the spike receptor-binding domain antigen using an ELISA at two centers in Philadelphia from April 4 to June 3, 2020. The results demonstrated that 80/1293 (6.2%) parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies (Table 2) (Flannery et al., 2020). Another study at three university hospitals in Spain showed that 54/372 (15%) women in the first trimester of pregnancy and 71/502 (14%) women in the third trimester had anti-SARS-CoV-2 IgG, IgM, or IgA using the VIRCLIA test (Vircell Microbiologist, Granada, Spain) (Crovetto et al., 2020).

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 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 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, Gallian et al. observed that the proportion of seropositivity was significantly lower in group O donors than in other donors (1.32% vs 3.86%, p = 0.014) (Gallian et al., 2020).

Patients undergoing hemodialysis are also at risk of COVID-19 transmission due to the need for frequent hospital stays, and therefore the difficulty in maintaining physical distancing (Yau et al., 2020, Tang et al., 2020, Arslan et al., 2020). The seroprevalence in hemodialysis patients ranged from 2.8% (16/563) to 3.6% (35/979) in a study in China (Xu et al., 2020). Another study showed the overall SARS-CoV-2 seroprevalence to be 36.2% (129/356) in hemodialysis patients, and 40.3% (n = 52) of them were asymptomatic or had negative PCR results (Clarke et al., 2020).

Association of seroprevalence rates with the country’s incidence of COVID-19

In this review, no significant association was found between the incidence of COVID-19 cases and the associated seroprevalence (Table 1). Even within the same country, the seroprevalence ranged from 0.1% to 12.5% in the USA, and from 0.05% to 4.0% in Brazil (Amorim Filho et al., 2020, Havers et al., 2020, Ng et al., 2020, Rosenberg et al., 2020, Silveira et al., 2020, Sood et al., 2020). These findings may be due to the fact that anti-SARS-CoV-2 antibody seroprevalence varies according to the different study countries/regions, study populations, timing during the period of the COVID-19 pandemic, and methods used for serology testing. Therefore, the seroprevalence reported in this article can only reflect the situation of the time and place in which the surveillance investigation was performed and with the specific test method used. In fact, the number of COVID-19 cases is still growing rapidly, and given the time-sensitivity, a true estimation of the epidemiology of SARS-CoV-2 infection remains a great challenge. Therefore, such seroprevalence surveillance should be continued and is necessary to estimate the burden of COVID-19.

Conclusions

The seroprevalence of anti-SARS-CoV-2 antibody can vary across different regions and can increase over time during longitudinal follow-up. Although HCWs, especially those caring for COVID-19 patients, are considered a high-risk group, the seroprevalence in this group may not be higher than that observed in other groups if they wear adequate PPE. Regarding sex, no statistically significant difference was found between male and female subjects. Some studies have shown that children have a lower risk than other age groups, while others have not. Finally, the seroprevalence can vary according to different populations, such as in pregnant women and patients undergoing hemodialysis; however, relevant studies are limited. Therefore, further continued surveillance of seroprevalence is warranted to estimate and monitor the growing burden of COVID-19.

Funding

No funding was required.

Ethical approval

No ethical approval sought.

Conflict of interest

We declare no conflict of interest.

References