Letter to the Editor

Ann Lab Med 2022; 42(5): 612-615

Published online September 1, 2022

Copyright © Korean Society for Laboratory Medicine.

Investigation of the Neutralizing Antibody Response of Healthcare Workers at a Korean University Hospital Six Months After the Introduction of the COVID-19 Vaccine

Seong-Ho Choi, M.D., Ph.D.1* , Ji Young Park, M.D., Ph.D.2* , Joung Ha Park, M.D., Ph.D.1 , Min-Chul Kim, M.D., Ph.D.1 , Oh Joo Kweon, M.D., Ph.D.3 , and Jin-Won Chung, M.D., Ph.D.1

1Division of Infectious Diseases, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea; 2Department of Pediatrics, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea; 3Department of Laboratory Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea

Correspondence to: Jin-Won Chung, M.D., Ph.D.
Division of Infectious Diseases, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea
Tel: +82-2-6299-1420, Fax: +82-2-825-7571, E-mail:

*These authors equally contributed to this study.

Received: November 16, 2021; Revised: December 11, 2021; Accepted: April 7, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dear Editor,

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China in December 2019, continues after 22 months [1]. As of late February 2021, Korea began to participate in the global COVID-19 vaccination program [2]. Healthcare workers (HCWs), the elderly, and employees of nursing homes or nursing hospitals were designated as the first individuals to be vaccinated in Korea [2]. HCWs were vaccinated with two different COVID-19 vaccines: those caring for COVID-19 patients were administered BNT162b2, while other HCWs were administered ChAdOx1 nCoV-19 [2]. As it had been six months since the vaccines were introduced, we investigated the neutralizing antibody (NAb) response against SARS-CoV-2, which is highly predictive of protection against COVID-19, using sera obtained from vaccinated HCWs [3].

The GenScript SARS-CoV-2 surrogate virus neutralization test (SVNT) kit (GenScript Biotech Corporation, Piscataway, NJ, USA) and Euroimmun anti-SARS-CoV-2 IgG ELISA (Euroimmun Medical Laboratory Diagnostics AG, Lübeck, Germany) were used. The result readings have been described in a recent study by our group [4]. The Institutional Review Board of Chung-Ang University Hospital (Seoul, Korea) approved this study (2051-001-415).

At Chung-Ang University Hospital, 259 HCWs were vaccinated with BNT162b2 and 1,356 HCWs with ChAdOx1 nCoV-19. Fifty-one HCWs vaccinated with BNT162b2 participated in this study. We previously reported NAb responses one month after the first dose of ChAdOx1 nCoV-19 in 182 HCWs, 115 of whom participated also in the current study [4]. The dates of vaccination and serum sample collection are listed in Table 1. Additionally, sera of four patients two months after COVID-19 diagnosis were tested.

Table 1 . Dates of vaccination and sampling, demographic data, and antibody responses of HCWs vaccinated with BNT162b2 or ChAdOx1 nCoV-19 at a university hospital in Korea

VariablesHCWs vaccinated with BNT162b2 (six months after first dose) [A] (N=51)HCWs vaccinated with ChAdOx1 nCoV-19 (six months after first dose) [B] (N=115)P [A] vs. [B]HCWs vaccinated with ChAdOx1 nCoV-19 (one month after first dose) [C] (N=182)P [A] vs. [C]
Date of vaccination
First doseMarch 11–12, 2021March 4–10, 2021March 4–10, 2021
Second doseApril 1–2, 2021May 20–25, 2021
Date of samplingSeptember 9–14, 2021September 9–14, 2021April 12–16, 2021
Male sex16 (31.4%)36 (31.3%)0.9965 (35.7%)0.57
Median age (SD)39.5 (9.8)40.0 (10.5)0.7639.0 (10.5)0.76
Age group (yr)0.750.72
20–2911 (21.6%)21 (18.3%)44 (24.2%)
30–3914 (27.5%)39 (33.9%)56 (30.8%)
40–4917 (33.3%)30 (26.1%)43 (23.6%)
50–598 (15.7%)20 (17.4%)33 (18.1%)
60–691 (2.0%)5 (4.3%)6 (3.3%)
Euroimmun IgG
Positive50/50 (100%)109 (94.8%)0.18162/180 (90.0%)0.015
Median (IQR)4.73 (3.75–5.37)2.68 (1.92–3.92)< 0.00012.79 (1.72–4.14)< 0.0001
Positive51 (100%)112 (97.4%)0.55148 (81.3%)0.001
Median (IQR)89.2 (79.6–93.2)72.0 (51.5–87.2)< 0.000151.3 (35.9–64.7)< 0.0001

Abbreviations: HCWs, healthcare workers; SD, standard deviation; IQR, interquartile range; SVNT, surrogate virus neutralization test.

COVID-19 patients showed higher median IgG (interquartile range [IQR], 8.206 [7.448–8.420] vs. 4.726 [3.749–5.367], P<0.0001) and SVNT (97.94 [97.63–98.02] vs. 89.19 [79.63–93.24], P=0.0379) values than HCWs vaccinated with BNT162b2. HCWs six months after the first dose of BNT162b2 showed higher median IgG and SVNT values than HCWs six months after the first dose of ChAdOx1 nCoV-19. HCWs six months after the first dose of ChAdOx1 nCoV-19 had higher SVNT values than HCWs one month after the first dose (Fig. 1 and Table 1).

Figure 1. Antibody responses six months after COVID-19 vaccine introduction at a university hospital in Korea. (A) Nab levels as measured by percentage inhibition in SVNT readings. (B) Antibody levels as measured using Euroimmun IgG ELISA. The violin plots show the distribution of the antibody responses. The thick horizontal line and upper and lower thin lines indicate the median, 25th percentile, and 75th percentile, respectively. Each hollow circle represents a study participant.
Abbreviations: Nab, neutralizing antibody; SVNT, surrogate virus neutralization test; Dx, diagnosis.

HCWs vaccinated with ChAdOx1 nCoV-19 showed significantly lower neutralization activity than HCWs vaccinated with BNT162b2 at six months after COVID-19 vaccine introduction. NAb levels are considered correlates of protection against SARS-CoV-2 [5]. Vaccine-induced NAbs or adoptive transfer of NAbs protected rhesus macaques against SARS-CoV-2 challenge in a dose-dependent manner [6, 7]. Laboratory data from human vaccine trials and real-world outbreaks have shown that the NAb level is an inverse correlate of risk of SARS-CoV-2 or breakthrough infection [3, 5, 8]. Although the appropriate NAb level for protection against breakthrough infection has not been determined yet, the lower neutralization activity in HCWs vaccinated with ChAdOx1 nCoV-19 than in those vaccinated with BNT162b2 suggests that the former are more vulnerable to breakthrough infection than the latter. Booster vaccination is recommended at six months after receiving the primary series of BNT162b2 [9]. Therefore, ChAdOx1 nCoV-19 vaccine recipients with substantially lower NAb levels should receive the booster dose as soon as possible. Given that NAb levels were very low in the relatively young and healthy HCWs, elderly, or individuals with underlying medical conditions may be at greater risk of breakthrough infection. Unlike in the USA and Israel, where mRNA vaccines were administered, ChAdOx1 nCoV-19 was more frequently administered than mRNA vaccines until July 2021 in Korea. Booster vaccination of ChAdOx1 nCoV-19-vaccinated individuals is an important way in controlling COVID-19 spread in Korea.

In this cross-sectional study, individuals in the BNT162b2 group were tested at only one timepoint after vaccination; therefore, it is unknown whether NAb levels decreased six months after vaccination with BNT162b2. In a recent Greek study, the SVNT values of 31 COVID-19 patients 50 days after hospitalization and those of 219 HCWs 50 days after vaccination were nearly similar (median, 96.45% vs. 96.36%) [10]. The significantly lower SVNT values in HCWs six months after BNT162b2 vaccination (89.19%) than those in COVID-19 patients after two months (97.94%) (P=0.0379) may indicate that the NAb levels in the BNT162b2 group tended to decrease. Because of insufficient data in the current study, further research is needed to clarify this.

Considering the neutralizing activity in HCW sera six months after COVID-19 vaccine introduction, booster vaccination should be considered first for individuals who received ChAdOx1 nCoV-19 at the start of the Korean vaccine program.

Conceptualization: Chung JW; Data curation: Choi SH, Park JY; Formal analysis: Choi SH; Funding acquisition: Chung JW; Investigation: Choi SH, Park JY, Chung JW; Methodology: Choi SH, Kweon OJ; Project administration: Chung JW; Resources: Chung JW; Software: Choi SH; Supervision: Chung JW; Validation: Park JY, Park JH, Kim MC, Kweon OJ; Visualization: Choi SH; Writing–original draft: Choi SH, Park JY; Writing–review & editing: Park JH, Kim MC, Kweon OJ, Chung JW.

  1. WHO. WHO Director-General's opening remarks at the media briefing on COVID-19-11 March 2020. (Updated on March 2022).
  2. Korea Disease Control and Prevention Agency (KDCA). COVID-19 vaccination to begin this week. News Room, Press Release, February 22, 2021. (Updated on February 2021).
  3. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med 2021;27:1205-11.
    Pubmed CrossRef
  4. Park JY, Choi SH, Chung JW, Hwang MH, Kim MC. Systemic adverse events and use of antipyretics predict the neutralizing antibody positivity early after the first dose of ChAdOx1 coronavirus disease vaccine. J Clin Med 2021;10:2844.
    Pubmed KoreaMed CrossRef
  5. Gilbert PB, Montefiori DC, McDermott AB, Fong Y, Benkeser D, Deng W, et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science 2022;375:43-50.
    Pubmed CrossRef
  6. Yu J, Tostanoski LH, Peter L, Mercado NB, McMahan K, Mahrokhian SH, et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science 2020;369:806-11.
    Pubmed KoreaMed CrossRef
  7. McMahan K, Yu J, Mercado NB, Loos C, Tostanoski LH, Chandrashekar A, et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 2021;590:630-4.
    Pubmed KoreaMed CrossRef
  8. Addetia A, Crawford KHD, Dingens A, Zhu H, Roychoudhury P, Huang ML, et al. Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with a high attack rate. J Clin Microbiol 2020;58:e02107-20.
    Pubmed KoreaMed CrossRef
  9. Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Kalkstein N, et al. Protection of BNT162b2 vaccine booster against COVID-19 in Israel. N Engl J Med 2021;385:1393-400.
    Pubmed KoreaMed CrossRef
  10. Trougakos IP, Terpos E, Zirou C, Sklirou AD, Apostolakou F, Gumeni S, et al. Comparative kinetics of SARS-CoV-2 anti-spike protein RBD IgGs and neutralizing antibodies in convalescent and naïve recipients of the BNT162b2 mRNA vaccine versus COVID-19 patients. BMC Med 2021;19:208.
    Pubmed KoreaMed CrossRef