PHWR Public Health Weekly Report

Following the initial outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, in December 2019, the World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2020. After more than 3 years of ongoing surveillance, the global public health emergency concluded on May 5, 2023. A dashboard and interactive platform have been established through the WHO/Europe COVID-19 Information Hub to continuously monitor the disease [1]. In the Republic of Korea (ROK), the first confirmed case of COVID-19 was a Chinese woman in her 30 who arrived at Incheon International Airport on January 20, 2020. By August 31, 2023, ROK had officially recorded 34,571,873 domestic confirmed cases and 35,934 deaths, amounting to a fatality rate of 0.1%. Subsequently, the government discontinued the investigation of all COVID-19 cases [2]. During this national emergency, ROK established the Korea Disease Control and Prevention Agency (KDCA) in September 2020. Concurrently, the Division of Laboratory Diagnosis and Analysis at the Capital Regional Center for Disease Control and Prevention was created. This new division conducted 28,401 COVID-19 tests in 2021 and 21,234 in 2022, employing a 365-day imported COVID-19 surveillance system and a rapid reporting system that delivers test results within 6 hours of receiving the test samples [3,4]. To address the continual emergence of alpha, beta, gamma, delta, and omicron variants, along with their subvariants and recombinant forms, which have impacted the risk profile of the virus, including its transmissibility, severity, and immune evasion, the Division of Laboratory Diagnosis and Analysis actively participated in the KDCA’s COVID-19 Genomic Surveillance project from February 2021 to March 2023. During this period, it analyzed 13,098 variants introduced from outside ROK and reported various COVID-19 variants, including recombinant ones, to aid in establishing national epidemic prevention strategies for a preemptive response [5,6]. In this article, we present the results of our testing and variant analysis of imported COVID-19 in 2023, conducted in response to the policy shift from classifying COVID-19 as a class 2 to a class 4 legal communicable disease and transitioning from total surveillance to surveillance based on positive samples. This information provides foundational data for developing preventive measures to prepare for future imported infectious diseases like COVID-19 [2].

1. Imported COVID-19 Samples

The Division of Laboratory Diagnosis and Analysis at the Capital Regional Center for Disease Control and Prevention performed COVID-19 tests on 5,027 samples collected from symptomatic international arrivals during their quarantine at Incheon Airport National Quarantine Station (including the Gimpo Airport Branch) and Incheon National Quarantine Station in the Seoul metropolitan area in 2023. Of these samples, 1,573 tested positive for COVID-19. Additionally, 530 samples from international travelers were identified as COVID-19 positive through private testing centers at Incheon International Airport, including EONE Laboratories, Myongji Hospital, and Inha University Hospital. Together, these 2,103 samples (1,573+530) were analyzed for COVID-19 variants. Samples referred for COVID-19 testing from quarantine stations at airports and ports totaled 4,966 from Incheon International Airport, six from Gimpo International Airport, and 55 from Port of Incheon. Furthermore, the number of imported positive samples referred from private testing centers for variant analysis included 342 from EONE Laboratories, 158 from Myongji Hospital, and 30 from Inha University Hospital (Table 1).

Table 1 The status of COVID-19 diagnostic testing and variant analysis for respiratory symptomatic individuals from abroad in 2023

2023 (Jan–Dec)	National Incheon Airport Quarantine Station			National Incheon Quarantine Station		Total		Private diagnostic testing centers at Incheon International Airport			Total	Grand (total)
	Incheon International Airport	Kimpo International Airport		Incheon Port				EONE Laboratories	Myongji Hospital	Inha University Hospital
Testing request	4,966	6		55		5,027		342	158	30	530	5,557
COVID-19 positive	1,566	5		2		1,573		-	-	-	530	2,103
Positive rate (%)	31.5	83.3		3.6		31.3		-	-	-	100.0	-
Variant analysisa) (rt-PCR/NGS)	1,517 (51/1,466)	5 (0/5)		2 (1/1)		1,524 (52/1,472)		309 (130/179)	136 (63/73)	29 (21/8)	474 (214/260)	1,998 (266/1,732)
Variant analysis rate (%)	96.9	100.0		100.0		96.9		90.4	86.1	96.7	89.4	95.0

^a)Methods for analyzing COVID-19 variants: rt-PCR, NGS. COVID-19=coronavirus disease 2019; rt-PCR=real-time reverse transcription polymerase chain reaction; NGS=next generation sequencing..

2. Methods for COVID-19 Testing and Variant Analysis

For COVID-19 testing, real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was conducted following the official COVID-19 laboratory testing guidelines [7]. The COVID-19 positivity was determined based on the cycle threshold (Ct) values of the open reading frame ab (ORFlab) and envelope (E) genes, which are the primary targets for COVID-19 detection. Variant analysis was conducted based on these test results. Whole-genome sequencing using next generation sequencing technology targeted the ORFlab or ribonucleic acid (RNA)-dependent RNA polymerase genes for samples with a Ct value of 25 or lower. For samples with a Ct value of 33 or less, a real-time PCR test was employed to identify the five major variants (alpha, beta, gamma, delta, and omicron) [5].

1. COVID-19 Tests

From January to December 2023, a total of 5,027 imported COVID-19 suspected samples were referred to quarantine stations in the Seoul Metropolitan Area, with a positive rate of 31.3% (1,573 cases). This rate was higher than that of 5.0% (1,423 out of 28,401 cases) in 2021 and 29.0% (6,149 out of 21,234 cases) in 2022 [3,4]. Specifically, the positive rates in 2023 were 31.5% at Incheon International Airport, 83.3% at Gimpo International Airport, and 3.6% at Port of Incheon. Until August 31, when COVID-19 was reclassified as a class 4 infectious disease, the average number of samples requested weekly from January to August was 142, with a peak of 450 samples in the first week of January and a low of two samples in the 35th week of August. The highest weekly positive rate was 55.4% in the 22nd week of June, and the lowest was 13.8% in the 7th week of February. Following the reclassification to class 4, similar to influenza, the average weekly number of received samples dropped significantly to 4, totaling 67 samples from September to December (Figure 1).

Figure 1. Weekly status of COVID-19 diagnostic testing in 2023
COVID-19=coronavirus disease 2019.

2. Status of Imported COVID-19 Cases

Of the 5,027 international arrivals referred for COVID-19 testing during the quarantine phase, individuals hailed from 52 countries. The majority were Koreans (4,407, 87.7%), followed by arrivals from China (258, 5.1%), the United States (USA) (64, 1.3%), Japan (42, 0.8%), and the Philippines (31, 0.6%), with the remaining 137 cases were from across 42 other countries (2.7%) (Figure 2A). A total of 83 countries were the origin of departure for these cases, with the top origins being Japan (794, 15.8%), Vietnam (542, 10.8%), the USA (393, 7.8%), Thailand (378, 7.5%), and China (371, 7.4%). The highest COVID-19 positive rates among these were from Taiwan (47.7%), Australia (43.9%), Switzerland (42.4%), and Indonesia (18.5%) (Figure 2B). In 2023, the major countries of departure for cases (2,103) analyzed for COVID-19 variants were China (454, 21.6%), Japan (263, 12.5%), Vietnam (173, 8.2%), the USA (161, 7.7%), and Thailand (137, 6.5%). Notably, arrivals from China dominated in January and February following the lifting of most Chinese COVID-19 restrictions in December 2022, while arrivals from Japan and Vietnam were more frequent from April through July (Figure 3). January saw a record 553 confirmed cases from 33 countries, while in December, there were only four confirmed COVID-19 cases from three countries, as global relaxations in COVID-19 restrictions led to a sharp decrease in sample requests.

Figure 2. Nationality of respiratory symptomatic individuals from abroad and positive rates by countries of departure
(A) Nationality of international arrivals. (B) Positive rate by top 20 countries of departure. COVID-19=coronavirus disease 2019; USA=United States of America; UK=United Kingdom.

Figure 3. Monthly status of departure countries of coronavirus disease 2019 confirmed cases from abroad subject to variant analysis
USA=United States of America.

3. Analysis of COVID-19 Variants

Of the total 2,103 COVID-19 samples, 1,998 (95.0%) were analyzed for omicron variant typing (Table 1). Based on the Ct values from COVID-19 tests, 1,732 samples (86.7%) underwent whole-genome sequencing for recombinant and omicron subvariants, while the remaining 256 samples (13.3%) were tested through real-time PCR for the five major variants, confirming 100.0% of them as the omicron type. Variant analysis was conducted on 1,517 samples from Incheon International Airport, five from Gimpo International Airport, two from Port of Incheon, 309 from EONE Laboratories, 136 from Myongji Hospital, and 29 from Inha University Hospital. The variant analysis rate was 96.9% for quarantine station-referred samples and over 86.1% for those from private medical centers (Table 1).

Whole-genome sequencing helped identify several omicron subvariants introduced into ROK from other countries during 2023: the BA.2 family (233 cases, 13.5%), BA.5 family (242 cases, 14.0%), recombinant XBB family (1,239 cases, 71.5%), and seven other recombinant variants (18 cases, 1.0%). The recombinant XBB family subvariants, including XBB.1.5 (244 cases, 14.1%), XBB.1.9.1 (173 cases, 10.0%), XBB.1.16 (172 cases, 9.9%), XBB.2.3 (44 cases, 2.5%), and XBB.1.9.2 (43 cases, 2.5%), were predominantly introduced into ROK (Table 2). In the analysis of variants designated by WHO as variants of interest and variants under monitoring, the first half of the year saw the identification of BN.1 (five cases), CH.1.1 (20 cases), and CJ.1 (six cases) within the BA.2.75 family. Notably, the JN.1 variant of the BA.2.86 family, projected as the dominant variant in the country in 2024, had three cases reported in December from China, Indonesia, and Singapore (Supplementary Figure 1; available online, Table 2). Similarly, the BA.5 family, akin to the BA.2.75 family, was identified in March with major subvariants BF.7 (20 cases), BQ.1 (three cases), and BQ.1.1 (39 cases). The imported omicron recombinant XBB family was consistently observed throughout the year. Notable surveillance variants such as XBB.1.16 (172 cases), XBB.1.5 (244 cases), and XBB.1.19.1 (173 cases) were primarily introduced in the first half of the year, mainly from Vietnam, the USA, and Japan. Additionally, HF.1 (a subvariant of XBB.1.16) and EG.5 and HV.1 (subvariants of XBB.1.9.2) were identified in May (Philippines), September (nine countries including Japan), and October (USA and Qatar), respectively. Apart from the XBB family, new recombinants were detected by July, with XBF variants being the most introduced recombinant variants to the country (10 cases total), 40.0% originating from Australia.

Table 2 Monthly status of whole genome sequencing analysis for VOI and VUM of omicron

Omicron	Subvariants	Monthly COVID-19 variant analysis												Analysis count (%)	No. of departure countries	Country with the most variant entries into Korea (no. of variants)
		1	2	3	4	5	6	7	8	9	10	11	12
BA.2.* (233, 13.5%)	BA.2.3.*													9 (0.5)	6	Japan (2), Singapore (2), Philippines (2)
	BA.2.75.*													190 (11.0)	31	Japan (40)
	–BN.1													5 (0.3)	3	Japan (2), Türkiye (2)
	–CH.1.1													20 (1.2)	12	Vietnam (4)
	–CJ.1													6 (0.4)	6	Japan (1), USA (1), UK (1), France (1), Israel (1), Egypt (1)
	BA.2.86.1.1(=JN.1)													3 (0.2)	3	China (1), Indonesia (1), Singapore (1)
BA.5.* (242, 14.0%)	BA.5.*													180 (10.4)	28	China (90)
	–BF.7													20 (1.2)	3	China (18)
	–BQ.1													3 (0.2)	3	Spain (1), Italy (1), France (1)
	– BQ.1.1													39 (2.3)	15	Japan (12)
Recombinant XBB family (1,239, 71.5%)	XBB.*													547 (31.5)	47	Japan (87)
	XBB.1.16													172 (9.9)	29	Vietnam (31)
	–HF.1													1 (0.1)	1	Philippines (1)
	XBB.1.5													244 (14.1)	41	USA (50)
	XBB.1.9.1													173 (10.0)	35	Japan (19)
	XBB.1.9.2													43 (2.5)	21	Vietnam (4), France (4)
	–EG.5													13 (0.8)	9	Japan (3)
	–HV.1													2 (0.1)	2	USA (1), Qatar (1)
	XBB.2.3													44 (2.5)	20	Japan (9)
Other recombinant variants (18, 1.0%)	XAY													1 (0.1)	1	France (1)
	XBC													2 (0.1)	2	Vietnam (1), France (1)
	XBF													10 (0.6)	7	Australia (4)
	XBJ													2 (0.1)	1	Indonesia (2)
	XBK													1 (0.1)	1	Türkiye (1)
	XBL													1 (0.1)	1	Hong Kong (1)
	XBW													1 (0.1)	1	UK (1)
														1,732 (100.0)

BA.2.3.* includes all subvariants of BA.2.3; BA.2.75.* includes all subvariants of BA.2.75, except for BN.1., CH.1.1, and CJ.1; BA.5.* includes all subvariants of BA.5, except for BF.7, BQ.1, and BQ.1.1; XBB* includes all kinds of XBB subvariants, except for XBB.1.16, XBB.1.5, XBB.1.9.1, XBB.1.9.2 and XBB.2.3. VOI=variants of interest; VUM=variants under minitoring; COVID-19=coronavirus disease 2019; USA=United States of America; UK=United Kingdom..

Overall, the major origins of the notable imported subvariants varied monthly, with Japan as the predominant origin for the BA.2.75 family, China for the BA.5 family, and Japan, the USA, and Vietnam for the XBB family (Table 2).

In 2023, the Division of Laboratory Diagnosis and Analysis at the Capital Regional Center for Disease Control and Prevention conducted COVID-19 tests on respiratory symptomatic samples referred from the Incheon Airport National Quarantine Station, Incheon National Quarantine Station, and private medical centers within Incheon International Airport. A total of 5,027 samples were referred from these quarantine stations, yielding a COVID-19 positivity rate of 31.3% (1,573 cases). Of these, 1,732 positive samples were analyzed and found to include major WHO-designated omicron subvariants (e.g., BN.1, BF.7, and EG.5), through whole-genome sequencing. This effort was crucial in contributing to the quarantine response to prevent the introduction of COVID-19 into the country. However, with the downgrading of COVID-19 to class 4, the surveillance system shifted from total to positive sample surveillance, substantially reducing the number of sample requests from symptomatic respiratory cases. This shift necessitates exploring new methods to monitor imported pathogens. From January to May 2024, only 39 samples from internationally introduced cases were referred at the quarantine step in the Seoul Metropolitan Area—a stark decrease from the 4,286 cases in the same period the previous year, marking a 99.1% reduction. A total of 12 COVID-19 variants were analyzed, which confirmed the introduction of subvariants of BA.2.86 family including JN.1 family (seven cases from China and Thailand) and KP family (two cases from Taiwan and the United Kingdom) as well as HK family (two cases from Japan), a subvariant of XBB.1.9.2 family, and new recombinant XDP (one case from Taiwan).

As of June 2024, the WHO reported that JN.1 from the BA.2.86 family and EG.1 from the XBB.1.9.2 family continue to be detected globally as the dominant omicron subvariants. Additionally, subvariants of JN.1, including JN.1.7, KP.2, KP.3, and JN.1.18, were designated as variants under monitoring, indicating a continued global prevalence of the JN.1 family alongside a decrease in previously prevalent XBB subvariants [8]. Although these omicron subvariants have not considerably impacted vaccine efficacy or increased disease severity to date, ongoing characterization of COVID-19 variants through whole-genome sequencing alongside rapid testing is essential to prepare for potential new pandemics, given the unpredictable emergence of new variants.

Incheon International Airport, Gimpo International Airport, and the Port of Incheon, located in the Seoul Metropolitan Area, serve as major gateways for international arrivals in ROK and are pivotal in the surveillance and characterization of imported infectious diseases. To effectively prevent the entry of these diseases and implement robust quarantine measures, the Division of Laboratory Diagnosis and Analysis at the Capital Regional Center for Disease Control and Prevention plans to continue monitoring the emergence of new COVID-19 variants through a dedicated pathogen testing system in the country.

Ethics Statement: Not applicable.

Funding Source: The report was funded by Korea Disease Control and Prevention Agency.

Acknowledgments: We thank the Division of Emerging Infection Diseases at Korea Disease Control and Prevention Agency for supporting experimental materials & methods and private diagnostic testing centers (EONE Laboratories, Myongji Hospital, and Inha University Hospital) providing coronavirus disease 2019 positive specimens at Incheon International Airport.

Conflict of Interest: The authors have no conflicts of interest to declare.

Author Contributions: Conceptualization: EJL, HC, JGN. Data curation: EJL. Formal analysis: EJL, JSN. Methodology: SHH, SMP, YJK, JHH, HSJ, KRK, KSJ, CYL. Investigation: EJL, SHH. Project administration: EJK. Supervision: JGN. Writing – original draft: EJL. Writing – review & editing: JGN, HC, IHK.

Supplementary data are available online.