COVID-19 Vaccination Strategy and Evidence in Korea

Abstract

Coronavirus disease 2019 (COVID-19) has created major global challenges, with vaccination remaining the most effective measure to reduce severe outcomes and mortality. In Korea, six vaccines were approved, and the rapid rollout initiated in February 2021 contributed to comparatively low global mortality. As the epidemiological landscape of COVID-19 evolved and evidence on vaccine immunogenicity and safety accumulated, Korea adapted its vaccination strategies. During the 2024–2025 season, two mRNA vaccines (Pfizer-BioNTech and Moderna) and one recombinant protein vaccine (Novavax) targeting JN.1 lineage were administered primarily to high-risk groups. Beginning in October 2025, two mRNA vaccines (Pfizer-BioNTech and Moderna) adapted to LP.8.1 variant have been introduced as the updated 2025–2026 season formulations. Although safety concerns arose initially, Korean studies confirmed that COVID-19 vaccines provided strong effectiveness and acceptable safety, consistent with international findings. To enhance preparedness for future pandemics and epidemics, sustaining surveillance systems and maintaining updated vaccination policies are critical to ensure effective public health responses.

Graphical Abstract

INTRODUCTION

Coronavirus disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranging from mild symptoms to life-threatening complications.1 Since the first reported outbreak in late 2019,2 the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern (PHEIC).3 As of July 2025, WHO COVID-19 surveillance reported over 700 million confirmed cases and approximately 7 million deaths worldwide.4 The COVID-19 pandemic became a major public health concern, with increased risk of severe disease and mortality among older adults, pregnant women, and individuals with underlying medical conditions.5,6,7 The rapid development and global deployment of COVID-19 vaccines significantly reduced the disease’s impact,8 leading the WHO to declare the end of the PHEIC on May 5, 2023.9

In Korea, the first imported case was confirmed on January 20, 2020,10 followed by multiple epidemic waves.11 Despite periodic surges, Korea sustained comparatively low mortality through aggressive contact tracing, centralized quarantine, and strong public cooperation with social distancing and mask usage.12 After vaccine introduction in February 2021, Korea achieved broad nationwide coverage, resulting in marked reductions in severe cases and COVID-19–related mortality.11,12

This review provides an overview of the national COVID-19 vaccination program in Korea and summarizes findings from domestic studies evaluating vaccine effectiveness (VE) and safety. By contextualizing these outcomes, we aim to advance understanding of Korea’s vaccination strategy and offer insights for future pandemic preparedness.

COVID-19 VACCINATION POLICY AND IMPLEMENTATION IN KOREA

By 2025, six types of COVID-19 vaccines had been approved in Korea (Table 1, Fig. 1).13,14,15,16 The first approval, granted on February 10, 2021, was for ChAdOx1-nCoV-19, an adenoviral vector vaccine developed by AstraZeneca in collaboration with the University of Oxford, followed by Pfizer-BioNTech’s mRNA vaccine (BNT162b2). The national immunization program began on February 26, 2021, with these two vaccines, prioritizing healthcare workers caring for patients with COVID-19 and staff of long-term care facilities.13,17,18 Janssen’s adenoviral vector vaccine (Ad26.COV2.S) and Moderna’s mRNA vaccine (mRNA-1273) were subsequently approved.13,17

Table 1. COVID-19 vaccines authorized in Korea.

Platform	Vaccines	Vaccination rollout period	Primary series vaccination		Antigenic formulation update in Korea	Major safety concerns
			Early pandemic period (2021–2022)	Post-pandemic period (2022–2026)
Adenoviral vector	ChAdOx1 nCoV-19 (AstraZeneca)	February 2021	Two doses, 4–12 wk interval	Not recommended	Original (ancestral) only	Anaphylaxis (1.45 per million COVID-19 vaccine doses)14
	Ad26.COV2.S (Janssen)	June 2021	Single dose	Not recommended	Original (ancestral) only	TTS/VITT (0.20 per million ChAdOx1 doses)15
mRNA	BNT162b2 (Pfizer-BioNTech)	February 2021-used through 2025–2026 season	Two doses, 3–8 wk interval	Single dose, ≥ 3 mon after last COVID-19 vaccine	Original (ancestral) → bivalent (BA.1) → bivalent (BA.4/5) → monovalent (XBB.1.5)a → monovalent (JN.1) → monovalent (LP.8.1)	Anaphylaxis (1.45 per million COVID-19 vaccine doses)14
						Myocarditis (5.0 per million mRNA doses)15
	mRNA-1273 (Moderna)	June 2021-used through 2025–2026 season	Two doses, 4–8 wk interval	Single dose, ≥ 3 mon after last COVID-19 vaccine	Original (ancestral) → bivalent (BA.1) → bivalent (BA.4/5) → monovalent (XBB.1.5)a → monovalent (JN.1) → monovalent (LP.8.1)	Pericarditis (2.0 per million mRNA doses)15
Recombinant protein	NVX-CoV2373 (Novavax)	February 2022	Two doses, 4–8 wk interval	Single dose, ≥ 3 mon after last COVID-19 vaccine	Original (ancestral) → monovalent (XBB.1.5)a → monovalent (JN.1)a	Anaphylaxis (1.45 per million COVID-19 vaccine doses)14
	GBP510 (SK Bioscience)	September 2022	Two doses, 4 wk interval	Not recommended	Original (ancestral) only

COVID-19 = coronavirus disease 2019, TTS = thrombocytopenia syndrome, VITT = vaccine-induced immune thrombotic thrombocytopenia.

^aEmergency use authorization by Ministry of Food and Drug Safety.

Fig. 1. COVID-19 epidemic waves and vaccination strategy in Korea. Daily COVID-19 cases (blue vertical bars) during the mandatory surveillance are demonstrated by calendar days and variant predominance. Black arrows indicate dates of vaccine approval or EUA. CSR and CFR declined across successive variant periods.16 Mandatory surveillance ended on August 30, 2023, and transitioned to sentinel surveillance. CSR, proportion of severe/critical cases and deaths among confirmed cases; CFR, proportion of deaths among confirmed cases. Severe/critical cases were defined as patients requiring non-invasive ventilation, high-flow oxygenation, invasive ventilation, extracorporeal membrane oxygenation, or continuous renal replacement therapy.

COVID-19 = coronavirus disease 2019, EUA = emergency use authorization, CSR = case severity rate, CFR = case fatality rate, AZ = AstraZeneca, PF = Pfizer-BioNTech, MD = Moderna, JS = Janssen, NV = Novavax, SK = SK Bioscience.

The initial vaccination schedule consisted of two doses, except for Ad26.COV2.S, which required a single dose.19 To maximize first-dose coverage, longer intervals were adopted between the first and second doses. Vaccination then expanded to older adults in descending age groups—beginning with those aged ≥ 75 years, then ≥ 65 years, and ≥ 55 years—before extending to all adults.17,19 As the program progressed, additional vaccines addressed emerging needs. In early 2022, Novavax’s protein subunit vaccine (NVX-CoV2373) was introduced, offering an alternative for individuals with contraindications to mRNA vaccines. Later in 2022, a recombinant protein vaccine developed domestically by SK Bioscience (GBP510 adjuvanted with AS03) was authorized for primary immunization.13

Safety concerns influenced vaccine deployment, particularly rare adverse events (AEs) not detected in pre-licensure trials. Reports of thrombosis with thrombocytopenia syndrome (TTS), also termed vaccine-induced immune thrombotic thrombocytopenia, after ChAdOx1 and Ad26.COV2.S prompted age-specific restrictions and preferential use of mRNA vaccines.20,21 Meanwhile, myocarditis associated with mRNA vaccines, especially among younger males, required continued safety monitoring.22,23

Policy adaptations also reflected VE data. As evidence showed waning immunity,24,25 a third dose as a booster was recommended in October 2021, followed by a fourth dose for high-risk populations in February 2022 to restore immune protection (Fig. 2).19,26 According to the Korea Disease Control and Prevention Agency (KDCA), the fourth dose was initially recommended for immunocompromised individuals and residents of long-term care facilities and was subsequently expanded to residents of other facilities vulnerable to infection (i.e., mental health institutions and homeless shelters), as well as to individuals aged ≥ 18 years with underlying medical conditions and those aged ≥ 50 years.27

Fig. 2. Temporal evolution of coronavirus disease 2019 vaccination strategies and antigenic targets in Korea. Following initiation of the national vaccination program in February 2021, three vaccine platforms were used for primary series vaccination. mRNA vaccines became predominant during booster vaccination, while the 2022 winter season marked a transition from dose-based boosters to season-based, variant-adapted vaccination strategies.

AZ = AstraZeneca, JS = Janssen, PF = Pfizer-BioNTech, MD = Moderna, NV = Novavax, SK = SK Bioscience.

The emergence of the omicron variant, with marked immune escape, drove further program adjustments. In October 2022, bivalent mRNA vaccines containing antigens from both the ancestral SARS-CoV-2 strain and omicron subvariants (initially BA.1, later BA.4/5) were deployed.19,27 Accordingly, in December 2022, administration of third and fourth doses using monovalent vaccines targeting the ancestral strain was discontinued, and these vaccines were recommended only in a limited role for primary series vaccination.27

From March 2023, national vaccination policy led by KDCA evolved toward an annual vaccination strategy using updated, variant-adapted vaccines reflecting the dominantly circulating strains.28 Under this framework, updated vaccines replaced ancestral strain—based monovalent vaccines not only for booster doses but also for primary immunization. Consistent with this approach and ongoing viral evolution, monovalent XBB.1.5 vaccines replaced earlier formulations during the 2023–2024 season.27 These vaccines were authorized for use in the general population but were primarily recommended by the KDCA for individuals aged ≥ 65 years, immunocompromised individuals, and residents and staff of facilities vulnerable to infection.

During the 2024–2025 season, the KDCA recommended the monovalent JN.1-adapted vaccine for individuals aged ≥ 65 years, immunocompromised individuals aged ≥ 6 months, and residents of facilities vulnerable to infection.29 The Korean Society of Infectious Diseases (KSID) also issued its vaccination recommendation for the 2024–2025 season, adopting broader indications in accordance with international guidance.30 This recommendation included individuals with underlying medical conditions at high risk of severe COVID-19 and healthcare workers in facilities vulnerable to infection, and noted that vaccination could be considered for the general population aged ≥ 6 months. It should be noted that definitions of high-risk groups differ depending on whether KDCA-supported national vaccination policy or KSID clinical recommendations are being described. While KDCA guidance defines eligibility within the scope of publicly funded vaccination programs, KSID recommendations extend to clinically vulnerable populations beyond national program criteria. Accordingly, the KDCA recommended a narrower eligibility framework than that of the KSID, particularly with respect to immunocompromised individuals, such as those receiving active cancer treatment, undergoing immunosuppressive therapy, or having primary immunodeficiency. Nevertheless, the KDCA guidance allows for clinical judgment, permitting vaccination in additional individuals if deemed immunocompromised by the treating physician.

Beginning in October 2025, the LP.8.1-adapted mRNA vaccine has been recommended for use as the updated 2025–2026 season formulation. The KDCA retained the risk-based eligibility framework applied in the previous season, targeting individuals aged ≥ 65 years, immunocompromised individuals aged ≥ 6 months, and residents of facilities vulnerable to infection. Similarly, the KSID maintained its broader, risk-based recommendations, aligned with international guidance, for adults aged ≥ 65 years, individuals aged ≥ 6 months at high risk of severe COVID-19, and for residents of facilities at high risk, such as long-term care facilities and other facilities vulnerable to infection.31,32 This risk-based approach reflects the substantially lower incidence of severe COVID-19 among healthy younger individuals in the post-pandemic period (Fig. 1), while prioritizing sustained protection against severe outcomes in high-risk populations, including individuals aged ≥ 65 years.12,16 Accordingly, current COVID-19 vaccination policy in Korea emphasizes annual, seasonal vaccination in the fall, targeting high-risk populations rather than universal vaccination.

The risk-based approach in Korea is aligned with the global advisory process led by the WHO Technical Advisory Group on COVID-19 Vaccine Composition, which convenes twice-yearly to review the evolution of SARS-CoV-2, assess the performance of existing vaccines, and issue statements on antigen composition of COVID-19 vaccines. While current COVID-19 vaccine updates have generally been implemented on an annual basis, vaccination strategies may be modified according to epidemiologic conditions. In addition, some countries recommend a biannual vaccination strategy for higher-risk populations (i.e., moderately or severely immunocompromised individuals), taking waning immunity into consideration.32 In Korea, the 2025–2026 season guidance from the KDCA31 and the KSID32 recommends annual vaccination; however, the KSID has noted that an additional dose at a 6-month interval may be considered for adults aged ≥ 65 years or for individuals who are moderately or severely immunocompromised. Future vaccination strategies are therefore expected to remain flexible, depending on COVID-19 epidemiologic conditions, emerging variants, COVID-19 seasonality, and policy considerations such as cost-effectiveness.

COVID-19 VACCINE COVERAGE IN KOREA

As of July 2025, the cumulative administration of COVID-19 vaccines in Korea totaled 146,239,641 doses, including 44,896,340 first doses, 42,971,170 second doses, and 33,644,457 third doses.15 A 2025 white paper from the KDCA reported nationwide COVID-19 vaccination coverage rate of 84.0%, 83.3%, and 63.1% for the first, second, and third doses, respectively.27

The fourth dose, representing the first risk-based vaccination, accounted for 7,598,143 administered doses,15 while vaccination coverage among individuals aged ≥ 50 years was 33.0%.27 During the 2022 winter season, 6,776,470 vaccine doses were administered to the general population,15 and vaccination coverage among individuals aged ≥ 50 years was 33.8%.27

For the 2023–2024 season, 5,036,707 doses of seasonal COVID-19 vaccine were administered,15 and vaccination coverage among individuals aged ≥ 65 years reached 41.3% as of May 1, 2024.27 As of July 2025, a total of 5,050,042 doses of 2024–2025 season COVID-19 vaccine doses had been administered, a level comparable to that observed during the 2023–2024 season.15

From the initiation of the national COVID-19 vaccination program through July 2025, vaccines targeting the ancestral SARS-CoV-2 strain accounted for 88.3% (129,180,154 doses) of all vaccinations. Among these, Pfizer-BioNTech represented the largest share (81,183,130; 62.8%), followed by Moderna (25,156,453; 19.5%), AstraZeneca (20,348,863; 15.8%), Janssen (1,511,664; 1.2%), Novavax (974,574; 0.8%), and SK Bioscience (5,470; < 0.1%).15

A cross-sectional study conducted in August 2022 reported a seropositivity rate of 97.6% for anti-spike protein antibodies. In the same study, seropositivity for anti-nucleocapsid antibodies—an indicator of prior natural SARS-CoV-2 infection—was 57.1%, suggesting that vaccination contributed substantially to population immunity.33

EFFECTIVENESS OF COVID-19 VACCINE IN KOREA

During nationwide mandatory surveillance period of COVID-19 in Korea (January 20, 2020–August 30, 2023), 34,572,554 confirmed COVID-19 cases, 38,112 severe or critical cases, and 35,605 deaths were reported.11 The case fatality rate decreased from 2.16% in 2020 to 0.91% in 2021, 0.09% in 2022, and 0.06% in 2023, alongside a reduction in case severity rate from 4.33% in 2020 to 0.14% in 2022 and 0.15% in 2023. Although absolute numbers of severe cases and deaths peaked during the omicron-dominant period due to high case volumes, the highest severity and fatality rates occurred before delta predominance.

Consistent with these epidemiologic trends, the benefits of COVID-19 vaccination have been demonstrated in numerous Korean studies evaluating real-world VE (Table 2).34,35,36,37,38,39,40,41,42 Early in the vaccination campaign using ancestral-strain vaccines, a national cohort study among individuals aged ≥ 18 years estimated VE at 63% against SARS-CoV-2 infection, 93% against severe disease, and 95% against death, confirming strong protection.34 Similarly, a nationwide cohort study among adolescents aged 12–18 years demonstrated comparable VE of 76–83% against laboratory-confirmed SARS-CoV-2 infection.35 Supporting these findings, an immunogenicity study showed that both BNT162b2 (Pfizer-BioNTech) and ChAdOx1 (AstraZeneca) produced high levels of neutralizing antibody seropositivity, particularly after completion of the second dose.43,44

Table 2. Summary of nationwide COVID-19 VE studies in Korea.

Studies	Study period	Study design	Predominant viral strain	Vaccine formulation	Study population	Comparators	VE (95% CI)	Key findings
Yi et al. (2022)34	March 2021–October 2021	Nationwide cohort study	Alpha, delta	mRNA (BNT162b2, mRNA-1273)	Individuals aged ≥ 18 yr	Primary series vs. unvaccinated	Laboratory-confirmed infectiona: 63%	Strong protection against severe disease and death in adults; modest protection against infection
				Adenoviral (ChAdOx-1, Ad26.COV2.S)			Severe diseasea,b: 93%
							Deatha: 95%
Kim et al. (2022)35	July 2021–January 2022	Nationwide cohort study	Delta	mRNA (BNT162b2)	Adolescents aged 12–18 yr	Two-dose primary series vs. unvaccinated	Laboratory-confirmed infection at 14–29 days post-vaccination:	High VE in adolescents; peak at 14–29 days, with waning VE against infection but sustained VE against severe disease
							- Age 12–15 yr: 76.55% (74.33–78.58%)
							- Age 16–17 yr: 83.49% (81.33–85.40%)
							- Age 18 yr: 82.79% (75.09–88.10%)
							Severe diseaseb at 14–29 days post-vaccination: 100% (100–100%) in all age group
Kim et al. (2022)36	February 2022–May 2022	Nationwide cohort study	Omicron BA.1/BA.2	mRNA (BNT162b2, mRNA-1273), adenoviral (ChAdOx-1) as primary series → mRNA as a 3rd and 4th dose	Immunocompromised, residents of LTCF	4th dose vs. 3rd dose vaccination	At ≥ 30 days post-vaccination;	Additional protection conferred by 4th dose (2nd booster); waning VE against infection beyond 30 days but sustained VE against critical infection and death
							Laboratory-confirmed infection: 22.28% (19.35–25.11%)
							Critical infectionc: 56.95% (29.99–73.53%)
							Death: 62.96% (34.18–79.15%)
Jang et al. (2023)37	March 2022–August 2022	Nationwide cohort study	Omicron BA.1/BA.2, BA.5	mRNA (BNT162b2)	Children aged 5–11 yr	Two-dose primary series vs. unvaccinated	Laboratory-confirmed infection at 15–30 days post-vaccination: 57.6% (51.6–62.8%)	Moderate protection against infection and strong protection against ICU admission and death in children; waning VE against infection beyond 30 days but sustained VE against ICU admission and death
							ICU admission or death at 15–30 days post-vaccination: 100% (100–100%)
Park et al. (2023)38	April 2022–August 2022	Nationwide cohort study	Omicron BA.2/BA.5	mRNA (BNT162b2, mRNA-1273), adenoviral (ChAdOx-1) as primary series → mRNA as a third and fourth dose	Individuals aged ≥ 60 yr	4th dose vs. 3rd dose vaccination	At 61–90 days post-vaccination;	Limited infection protection of 4th dose in the elderly during Omicron period; substantial reduction in critical infection and death
					Exclusion: immuno-compromised, residents of LTCF		Laboratory-confirmed infection: 17.3% (16.6–18.0%)
							Critical infectionc: 62.1% (45.5–73.7%)
							Death: 63.9% (35.9–79.7%)
Park et al. (2023)39	January 2022–August 2022	Nationwide cohort study	Omicron BA.1/BA.2	mRNA (BNT162b2, mRNA-1273), adenoviral (ChAdOx-1) as primary series → mRNA as a third and fourth dose	Individuals aged ≥ 60 yr	Homologous or heterologous fourth dose vaccination vs. unvaccinated	Death in,	Strong protection against critical infection and death with both homologous and heterologous 4th dose during Omicron period
							- Homologous mRNA (m-m-m-m): 96.1% (95.4–96.7%)
							- Heterologous 2-dose viral vector + 2-dose mRNA (v-v-m-m): 95.1% (94.5–95.6%)
							- Heterologous 1-dose viral vector + 3-dose mRNA (v-m-m-m): 90.8% (79.4–95.9%)
Kim et al. (2023)40	October 2022–January 2023	Nationwide cohort study	Omicron BA.5	BA.1-adapted bivalent mRNA (mRNA-1273.214)	Individuals aged ≥ 18 yr	Bivalent vaccine vs. no bivalent vaccine	Laboratory-confirmed infection: 42.4% (41.7–43.1%)	Restored and sustained protection against severe disease and death conferred by bivalent vaccine during Omicron period
							Severe diseaseb or death: 81.3% (76.3–85.3%)
							Death: 85.3% (78.5–89.9%)
Choi et al. (2024)41	January 2022–August 2023	Nationwide matched cohort study	Omicron BA.1/BA.2, BA.5, BN.1, XBB sublineages	Bivalent mRNA	Individuals aged ≥ 18 yr	Bivalent vaccine vs. unvaccinated	Severe diseaseb or death in,	Strong protection against severe disease or death conferred by bivalent vaccine during Omicron period, particularly among aged ≥ 65 yr or those without prior infection
							- no COVID-19 history: 86.32% (85.72–87.82%)
							- 1 COVID-19 history: 65.89% (58.31–70.72%)
							- ≥ 2 COVID-19 history: 54.99% (52.15–60.71%)
Jo et al. (2025)42	October 2023–June 2024	Population-based cohort study, nested case-control study	Omicron XBB sublineages (EG.5, HK.3), JN.1	XBB.1.5-adapted vaccined	Individuals aged ≥ 65 yr	XBB.1.5 vaccine vs. no XBB.1.5 vaccine	Self-reported infection: 54% (19–74%)	Moderate protection against self-reported infection in the elderly conferred by 2023–2024 season vaccination
							Self-reported infection or anti-N antibody seroconversion: 33% (7–51%)

COVID-19 = coronavirus disease 2019, CI = confidence interval, VE = vaccine effectiveness, LTCF = long-term care facility, ICU = intensive care unit.

^a95% CI not reported.

^bSevere disease was defined as COVID-19 requiring high-flow oxygen therapy, mechanical ventilation, extracorporeal membrane oxygenation, or continuous renal replacement therapy within 28 days of laboratory confirmation.

^cCritical infection was defined as COVID-19 requiring noninvasive or invasive ventilation, extracorporeal membrane oxygenation, or continuous renal replacement therapy.

^dThe vaccine platform was not specified in the study. During the study period, both mRNA (Moderna, Pfizer-BioNTech) and protein subunit (Novavax) vaccines were available.

Humoral immunity induced by two doses waned over time, with antibody responses markedly declining within 6 months after the second dose.44,45 This decline coincided with the spread of the delta variant. A nationwide cohort study estimated protective immunity at 6 months post-primary series to be 28.3% for ChAdOx1, 52.5% for BNT162b2, and 66.7% for heterologous vaccination with ChAdOx1 followed by BNT162b2.45 To address this reduction, booster vaccination was introduced in late 2021. Administration of a third (booster) mRNA dose restored neutralizing activity against both wild-type and delta variants in homologous and heterologous schedules.46,47 In early 2022, a fourth (second booster) dose was recommended for high-risk groups, including older adults. A nationwide cohort study reported the VE of the fourth dose against death in individuals aged ≥ 60 years as 96.1% for homologous mRNA vaccination and 95.1% for heterologous vaccination (two viral vector doses plus two mRNA doses).39 Substantial protection was also observed when comparing fourth- with third-dose recipients, with VE estimated at 62.1% against critical infection and 63.9% against death.38

With the circulation and evolution of the omicron variant, marked by immune evasion from ancestral-strain vaccination or prior infection, the introduction of bivalent BA.4/5 mRNA vaccines in late 2022 provided added protection beyond monovalent boosters. A retrospective cohort study estimated VE of the bivalent vaccine against critical infection as 86.3% compared with unvaccinated individuals, and 65.9% and 55.0% among those with one and two prior infections, respectively.41 Another cohort study reported that bivalent vaccination conferred 12.2% greater protection against COVID-19 infection compared with the monovalent vaccine.48 A further cohort study found the relative VE of the bivalent versus monovalent vaccine to be 42.4% against infection, 81.3% against critical infection, and 81.5% against death.40

During the 2023–2024 season, updated monovalent XBB.1.5 vaccines replaced earlier formulations, continuing the approach of variant-adapted boosters. A test–negative case–control study estimated relative VE of XBB.1.5 vaccination, compared with no XBB.1.5 vaccination, as 57.7% against symptomatic infection, 64.3% against hospitalization, and 65.5% against cases requiring oxygen therapy.49 Another multicenter test–negative case–control study reported a similar adjusted VE of 56.8% against symptomatic infection.50

During the 2024–2025 season, the dominant circulating sublineages belonged to the JN.1 lineage (e.g., JN.1, KP.2, KP.3). Monovalent JN.1 mRNA vaccines were authorized in Korea and recommended for high-risk groups, including adults aged ≥ 65 years, individuals with underlying medical conditions, residents of long-term care facilities, pregnant women, and healthcare workers.30 In addition, a monovalent JN.1 recombinant protein vaccine developed by Novavax received emergency use authorization, offering an option for individuals unable to receive mRNA vaccination. Effectiveness data for JN.1-specific vaccination in Korea remain limited. In the United States, interim estimates from the early 2024–2025 season indicated that updated COVID-19 vaccines targeting JN.1 lineage achieved VE of 45% against COVID-19—associated hospitalization in immunocompetent adults aged ≥ 65 years and 40% in immunocompromised adults of the same age group.51

Since October 2025, LP.8.1 variant—adapted mRNA vaccines have been introduced as the 2025–2026 season formulation, in accordance with recommendations from the WHO and other regulatory agencies.52,53,54 Although other variants, including NB.1.8.1 and XFG, have been rapidly increasing globally, the WHO has assessed that these variants exhibit only minimal immune escape compared with LP.8.1, with the overall risk considered low.55,56 Consequently, LP.8.1-adapted vaccines are expected to provide adequate protection against currently circulating strains. However, as real-world data on the effectiveness of LP.8.1-adapted vaccines are currently limited, continued monitoring and evaluation are warranted to verify their performance in the field.

SAFETY OF COVID-19 VACCINE IN KOREA

Since the start of the COVID-19 vaccination program, AEs have been documented in both clinical trials and post-marketing surveillance. In phase 3 trials of early mRNA and adenoviral vector vaccines,57,58,59,60 solicited local and systemic reactions such as injection-site pain, fatigue, fever, headache, and myalgia were frequently reported, whereas serious vaccine-related AEs were rare across platforms. Recombinant protein vaccines introduced later showed comparable safety profiles in clinical trials.61,62 As mass vaccination progressed, however, attention shifted toward rare but potentially severe AEs not fully captured in pre-licensure studies, and surveillance systems began recording a broader spectrum of events.

Since February 2021, the KDCA has conducted nationwide surveillance of AEs following COVID-19 vaccination.15,63 AEs are classified as non-serious or serious. Serious AEs include those resulting in death, intensive care unit admission, life-threatening illness, permanent disability, or adverse event of special interest (AESI) such as anaphylaxis, myocarditis, pericarditis, thrombosis with TTS, and Guillain–Barré syndrome.

Between February 2021 and July 2025, Korea’s post-authorization surveillance recorded 485,054 AE reports following 146,239,641 administered COVID-19 vaccine doses (3.32 per 1,000 doses).15 Of these, 465,019 (95.9%) were non-serious, 17,861 (3.7%) were serious, and 2,174 (0.4%) were post-vaccination death reports. The most frequently reported AEs were headache (23.4%), myalgia (22.8%), dizziness (14.4%), chest pain (13.4%), nausea (11.2%), and fever (9.4%).

Regarding myocarditis, one of the major AESI, 609 cases were reported in Korea through July 2025: 587 associated with mRNA vaccines (5.0 per million doses), 5 with recombinant protein vaccines (4.5 per million doses), and 17 with viral vector vaccines (0.78 per million doses).15 Another Korean nationwide study of COVID-19 vaccine-related myocarditis (VRM) between February and December 2021 identified 480 cases (1.08 per 100,000 persons).64 The highest incidence occurred in males aged 12–17 years (5.29 per 100,000), while the lowest was in females aged ≥ 70 years (0.16 per 100,000). The incidence of COVID-19 VRM was higher in men than in women (1.35 vs. 0.82 per 100,000; P < 0.001), with a declining incidence observed with increasing age in both sexes.64 In addition, VRM incidence varied by vaccine dose, with comparable incidence after the first and second dose (0.47 [95% confidence interval {CI}, 0.41 to 0.54] vs. 0.55 [95% CI, 0.48 to 0.63] per 100,000 persons), but a significantly lower incidence after the third dose (0.24 [95% CI, 0.17 to 0.32] per 100,000).64 These findings are consistent with surveillance reports from the United States and Europe, where mRNA vaccine-associated myocarditis was also predominantly observed in young men.65,66 Although most cases were mild with favorable short-term outcomes, 95 (19.8%) were severe and 21 (4.4%) were fatal.64

For pericarditis, 246 cases were reported in Korea through July 2025: 235 following mRNA vaccination (2.0 per million doses) and 11 following viral vector vaccination (0.5 per million doses).15 Another nationwide study identified 179 cases of vaccine-related pericarditis during February–December 2021, with no fatalities. However, 10 cases (5.6%) developed significant pericardial effusion requiring drainage.67 Although myocarditis and pericarditis have been observed, they remain rare and generally mild. Given that the risk of cardiac complications following SARS-CoV-2 infection exceeds that associated with vaccination,68 current evidence supports continued use of mRNA vaccines, including in younger populations. However, individuals, particularly young males, should be aware of this rare risk of cardiac complications and seek prompt medical evaluation if symptoms such as chest pain or shortness of breath occur after vaccination.

In the case of TTS, a major AESI of adenoviral vector vaccines, 216 suspected cases were reported; however, causality was confirmed in only four cases after ChAdOx1 vaccination (0.20 per million doses), including a fatal case in a 33-year-old man.69 Although the absolute risk was very low, the severity of outcomes led Korean health authorities to suspend adenoviral vector vaccines, consistent with regulatory actions in Europe and other regions where they were withdrawn from immunization programs.70

FUTURE DIRECTIONS

In Korea, the prompt rollout of COVID-19 vaccination was effective and contributed to comparatively low mortality worldwide. However, future research and policy efforts should focus on several priorities. First, the long-term safety and durability of vaccine-induced immunity remain to be clarified. Continued surveillance of COVID-19 and vaccine pharmacovigilance are needed to ensure safe and effective use, particularly in vulnerable groups such as older adults, children, and immunocompromised individuals. Second, the ongoing evolution of SARS-CoV-2 underscores the need for a rapid vaccine update system. Sustained genomic surveillance, coupled with timely development and deployment of updated vaccines, will be essential to mitigate the public health burden of COVID-19. Third, domestic vaccine research and development must be strengthened. To address local epidemiological heterogeneity and host-specific immune responses, the generation of domestic data is critical for developing context-specific strategies. Strategic investment in mRNA and other next-generation vaccine platforms, together with robust clinical trial infrastructure, will be necessary to achieve national self-sufficiency and ensure timely responses to emerging variants and future pandemic threats.

CONCLUSION

Despite initial safety concerns and uncertainties during the initial phase of the pandemic, COVID-19 vaccines demonstrated substantial effectiveness and acceptable safety. Their rollout in Korea has been central to the national pandemic response since February 2021. However, the continued evolution of SARS-CoV-2 variants and waning immunity have led to recurrent epidemics. These findings emphasize the importance of maintaining updated vaccination policies and reinforcing surveillance systems to support timely and effective public health responses.