key: cord-0697212-ijr0v9gl
authors: Kim, Yu Kyung; Minn, Dohsik; Song, Do Young; Lee, Chae Hoon; Ryoo, Nam Hee; Jeon, Chang-Ho; Song, Kyung Eun; Suh, Jang Soo; Chang, Soon Hee
title: Prevalence of SARS-CoV-2 Antibody in 2,935 Healthcare Workers at 6 Major Hospitals, Daegu, Korea
date: 2021-10-19
journal: J Korean Med Sci
DOI: 10.3346/jkms.2021.36.e294
sha: 42a0bea45d1adf599e74b20401893d7af3dafba6
doc_id: 697212
cord_uid: ijr0v9gl

BACKGROUND: In Korea, the first community outbreak of coronavirus disease 2019 (COVID-19) occurred in Daegu on February 18, 2020. This study was performed to investigate the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies in healthcare workers (HCWs) at 6 major hospitals in Daegu. METHODS: Blood specimens of 2,935 HCWs at 6 major hospitals in Daegu from January 2021 to February 2021 were collected. Every specimen was tested for antibody against SARS-CoV-2 using both Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Roche Diagnostics, Rotkreuz, Switzerland) and R-FIND COVID-19 IgG/M/A enzyme-linked immunosorbent assay kit (SG medical Inc., Seoul, Korea) as screening tests. If 1 or more of these screening test results was positive, 2 additional antibody tests were performed using Abbott Anti-SARS-CoV-2 IgG assay (Abbott, Abbott Park, IL, USA) and cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript USA Inc., Piscataway, NJ, USA). If 2 or more of the total 4 test results were positive, it was determined as positive for the antibody against SARS-CoV-2. RESULTS: According to the criteria of SARS-CoV-2 antibody positivity determination, 12 subjects were determined as positive. The overall positive rate of the SARS-CoV-2 antibody was 0.41% (12/2,935). Of the 12 subjects determined as positive, 7 were diagnosed with COVID-19, and the remaining 5 were nondiagnosed cases of COVID-19. CONCLUSION: In early 2021, the overall seroprevalence of SARS-CoV-2 antibody among HCW located in Daegu was 0.41%, and 0.17% excluding COVID-19 confirmed subjects. These results were not particularly high compared with the general public and were much lower than HCWs in other countries.

In Korea, the first coronavirus disease 2019 patient was detected on January 20, 2020. 1 The first community outbreak occurred in Daegu, starting with patient 31 on February of OD of the negative control (Avg. of NC) was calculated. Next, the cutoffs were calculated using the following formulas: positive cutoff = 1.1 × (Avg. of NC + 0.25), and negative cutoff = 0.9 × (Avg. of NC + 0.25). The assay results were determined as positive (sample OD ≥ positive cutoff ), negative (sample OD ≤ negative cutoff ), and borderline (positive cutoff > sample OD > negative cutoff ). When the result was borderline, the test was repeated with aliquot sample.

Abbott anti-SARS-CoV-2 IgG assay is a chemiluminescent microparticle immunoassay detecting IgG antibodies against the SARS-CoV-2 NP using an Architect i2000 instrument (Abbott). The assay reports a ratio of sample absorbance to calibrator absorbance using an assay-specific calibrator. The result was interpreted as a positive (index ≥ 1.4) or negative (index < 1.4) using an index value (ratio over the threshold value).

The cPass SARS-CoV-2 Neutralization antibody detection kit is a blocking ELISA for qualitative and direct detection of neutralizing antibodies to SARS-CoV-2. This assay was designed to mimic the virus-host interaction by direct protein-protein interaction using the purified receptor-binding domain (RBD) and the human ACE2 receptor protein (hACE2). The protein-protein interaction between HRP conjugated recombinant SARS-CoV-2 RBD ( 

In this study, the overall positive rate of SARS-CoV-2 antibody in HCWs was found to be 0.41% (12/2,935) , and 0.17% (5/2,925) excluding 10 COVID-19 confirmed subjects. These findings are similar to the result of a previous study, which reported 0.3% (1/309) seropositivity for SARS-CoV-2 among HCWs designated to confirmed In Daegu, the first large outbreak caused more than 6,000 cases in February and March 2020, and since then, the total cumulative number of cases had been 8,623 until February 2021. 4 Based on the population of 2,401,110 at the end of December 2020, the COVID-19 incidence rate in February 2021 in Daegu was 0.36% (8,623/2,401,110) (Fig. 2) . In this study, there were 10 confirmed cases of COVID-19, which was 0.34% of the total subjects, and it was found that there was little difference with the COVID-19 incidence rate in the general population of Daegu. Hospital E had the highest number of SARS-CoV-2 antibody-positive HCWs. However, it was thought that there was little difference between institutions except for COVID-19 confirmed cases ( Table 2) .

According to the results announced by Korean Disease Control and Prevention Agency, the positive rates of SARS-CoV-2 antibody among the 3rd participants of National Health Nutrition Survey (15 cities and provinces nationwide, from August 14 to October 31, 2020) and military camps (residents of Yungun training center, from September to October) were 0.22% (3/1,379) and 0.36% (25/6,859), respectively. 1 And the positive rates of antibodies in nondiagnosed participants, excluding those with previously confirmed cases, were 0.07% (1/1,377) and 0.22% (15/6,849), respectively. Therefore, the prevalence of SARS-CoV-2 6/9 https://jkms.org https://doi.org/10.3346/jkms.2021.36.e294

Prevalence of SARS-CoV-2 Antibody in Healthcare Workers Contact with COVID-19 patients − HCW = healthcare worker, COVID-19 = coronavirus disease 2019, SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2, ELISA = enzyme-linked immunosorbent assay, PCR = polymerase chain reaction, N/A = not available, OD = optical density. a antibody is not particularly high in HCWs compared with the general public. The subject hospitals were in charge of hospitalization and treatment for COVID-19 confirmed patients during the early pandemic, so it seemed that they performed prevention for infection successfully even in situations where the risk of exposure was particularly high.

A recent meta-analysis of 49 studies involving a total of 127,480 subjects documented that the overall seroprevalence for HCWs worldwide was 8.7% (95% confidence interval 6.7-10.9%), ranging from 0% to 45.3% among studies. North America (12.7%) was higher than Europe (8.5%), Africa (8.2%), or Asia (4%). 5 Thus, the results of the present study revealed that seroprevalence of HCWs in Daegu, Korea was much lower than those of the other countries, although there are many factors to consider such as different degree of contact with the COVID-19 patients, different assay kits used, timing of implementation, or other variable circumstances.

The neutralizing antibody to SARS-CoV-2 in individuals with COVID-19 experience was reported to have stable antibody titers for several months after infection. 6 Another study documented that the neutralizing antibody against SARS-CoV-2 among infected HCWs declined rapidly and might even be lost from 2 months after disease onset. 7 The neutralizing antibody was detected at 66.7% (8/12) among the antibody-positive participants. Moreover, 3 of the 12 COVID-19 confirmed subjects had neutralization rates of 18.8%, 19.7%, and 19.1%, respectively, which were very close to the cutoff value (20%). Those results were determined as negative in this case, but it would be appropriate to consider as positive with a slight decrease in titer.

A previous report demonstrated that the rates of antibody positivity according to commercial immunoassays were high (69.0-91.4%) at 8 months after infection, even in asymptomatic or mildly symptomatic participants. 8 Most of the confirmed cases in this study were infected during the initial outbreak. Therefore, it was shown that the titer of antibody against SARS-CoV-2 including neutralizing antibody were maintained for >10 months, and it seemed to persist for > 1 year ( Table 2) .

Even in the subjects without symptoms other than confirmed COVID-19, 5 cases were found to be positive for the SARS-CoV-2 antibody ( infections existed among the HCWs. Some of them did not have any contact with COVID-19 patients, and the route of infection was unclear. Antibodies were reported to be detected even among asymptomatic individuals without a history of COVID-19 or close contact with them. 9 Therefore, it is suggested that HCWs without symptoms or contact history will need to strictly follow the infection prevention policy.

As the SARS-CoV-2 antibody immunoassays may show different results, serological assessment by a single assay requires caution in interpretation and monitoring. 10 A metaanalysis reported sensitivity of 96.6-99.7% for chemiluminescent immunoassays, 84.3% for ELISAs, and 66.6% for lateral flow immunoassays, respectively, citing heterogeneity among different serologic test kits. 11 Park et al. 12 recommended using two or more immunoassays to increase the positive predictive value when the prevalence of COVID-19 is low. Accordingly, we used two immunoassay kits as screening test tools, including an ELISA and an ECLIA kit, to exclude false-positive or false-negative results. Positive results were additionally confirmed using another 2 immunoassay kits, including a neutralization antibody assay. The discrepant results among the kits were also found in this study. Only 3 out of 12 seropositive subjects tested positive in all 4 immunoassay kits. More research data are needed regarding differences in sensitivity, specificity, and results between antibody detection kits.

In conclusion, this study reported that overall seroprevalence of SARS-CoV-2 antibody among HCWs in Daegu, Korea was 0.41%, and 0.17% excluding COVID-19 confirmed subjects. Those results were not particularly high compared with the general public and much lower than HCWs in other countries. Because there are infections that are asymptomatic and have no contact history, it is necessary to follow the policy for the infection prevention among HCWs. In addition, because most HCWs do not have antibodies, vaccination is needed to protect the HCWs and the hospital visitors who will come into contact with them. 

Ministry of Health and Welfare (KR)

A brief telephone severity scoring system and therapeutic living centers solved acute hospital-bed shortage during the COVID-19 outbreak in Daegu

Serologic evaluation of healthcare workers caring for COVID-19 patients in the Republic of

Daegu Metropolitan City COVID-19 status

Seroprevalence of SARS-CoV-2 antibodies and associated factors in healthcare workers: a systematic review and meta-analysis

Comparison of serologic response of hospitalized COVID-19 patients using 8 immunoassays

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

IgG seroprevalence of COVID-19 among individuals without a history of the coronavirus disease infection in Daegu

Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers

Antibody responses 8 months after asymptomatic or mild SARS-CoV-2 infection

Performance comparison of five SARS-CoV-2 antibody assays for seroprevalence studies

The authors thank all healthcare workers (HCWs) in Daegu, Korea for their hard work during the COVID-19 pandemic and voluntary participation in this study.