PHWR Public Health Weekly Report

Respiratory infections caused by influenza and other respiratory viruses exhibit seasonal periodicity, resulting in numerous cases worldwide and posing severe health risks, particularly among immunocompromised elderly individuals and young children [1,2]. The Division of Emerging Infectious Diseases at the Korea Disease Control and Prevention Agency (KDCA) operates the Korea Respiratory Virus Integrated Surveillance System (K-RISS) to identify the major pathogens responsible for respiratory infections prevalent in the Republic of Korea (ROK), thereby contributing to the establishment of effective infection control policies based on pathogen characteristics. K-RISS collects data and specimens from 200 medical institutions nationwide (106 sentinel surveillance primary care clinics, 59 secondary and tertiary hospitals, five specialized diagnostic laboratories, and 30 long-term care hospitals) to monitor the epidemiological patterns of influenza and eight respiratory viruses (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], rhinovirus, adenovirus, bocavirus, metapneumovirus, parainfluenza virus, respiratory syncytial virus, human coronavirus). For influenza viruses circulating domestically, K-RISS performs genetic analyses to assess vaccine strain homology and antiviral drug resistance, isolates viruses from specimens, and conducts detailed characterization, including antigenic typing and antiviral phenotyping. These efforts provide critical scientific evidence to enable rapid responses to infectious diseases and inform vaccine policy development. Additionally, as a designated National Influenza Center, the Division of Emerging Infectious Diseases participates in the Global Influenza Surveillance and Response System operated by the World Health Organization (WHO). As part of this participation, the Division shares sentinel surveillance results through RespiMART, the WHO influenza virus surveillance database (https://www.who.int/tools/RespiMart), and provides domestic influenza virus isolates to WHO Influenza Collaborating Centers, thereby contributing to global preparedness for influenza outbreaks, pandemics, and vaccine strain selection. This manuscript aims to report the characteristics of influenza and respiratory virus detection patterns observed in ROK during the 2023–2024 season (from week 36 of 2023 to week 35 of 2024), along with the results of genetic, antigenic, and antiviral drug resistance analyses of isolated influenza viruses.

1. Testing for Viral Pathogens Causing Respiratory Infections

From September 3, 2023 to August 31, 2024 (the 2023–2024 season), real-time reverse transcription polymerase chain reaction tests for influenza and eight respiratory viruses were performed by Public Health and Environment Research Institutes in 18 metropolitan cities and provinces on 18,040 upper respiratory tract specimens collected from sentinel surveillance-participating medical institutions. The Division of Emerging Infectious Diseases at KDCA compiled these test results, analyzed the pathogen detection rates, and disseminated weekly surveillance findings through the “Sentinel Surveillance Newsletter for Infectious Diseases and Pathogens.” For influenza viruses, the specimens were first differentiated into types A and B. Type A specimens underwent subtype testing for H1 and H3, while type B specimens were tested for lineage classification into Victoria or Yamagata. Thus, influenza viruses were categorized into A(H1N1)pdm09, A(H3N2), B(Victoria), and B(Yamagata) for detailed analysis.

2. Characterization of Influenza Viruses

Positive influenza specimens underwent additional genetic and antigenic analyses for viral characterization. Phylogenetic analyses of the hemagglutinin gene were performed to assess similarity to vaccine strains, and genetic sequencing of the neuraminidase (NA) and polymerase acidic (PA) protein genes was conducted to identify the mutations associated with antiviral drug resistance. For virus isolation, specimens positive for A(H1N1)pdm09 and type B were inoculated into Madin-Darby canine kidney (MDCK) cells, while A(H3N2)-positive specimens were inoculated into MDCK-SIAT1 cells. Antiviral phenotypic analyses for drug resistance to Oseltamivir, Zanamivir, and Peramivir were performed on the propagated viruses. Additionally, antigenic characterization of domestic isolates was conducted using hemagglutination inhibition assays or focus reduction assays with antisera derived from ferrets immunized with vaccine strains [3].

1. Detection Status of Respiratory Viruses

During the 2023–2024 season, the influenza and SARS-CoV-2 viruses had the highest detection rates at 15.1% each, followed by rhinovirus (14.9%), adenovirus (9.9%), parainfluenza virus (5.6%), respiratory syncytial virus (5.0%), metapneumovirus (4.2%), human coronavirus (3.8%), and bocavirus (3.2%; Table 1). Adenovirus showed high detection rates early in the season, but stabilized around the annual average of approximately 10% after week 51. The SARS-CoV-2 virus detection rates fluctuated until week 29 of 2024, then sharply increased, reaching a peak in week 33 of 2024 (Figure 1). Age-specific analyses revealed that influenza virus (27.1%) predominated among school-aged children (7–12 and 13–18 years), the SARS-CoV-2 virus (26.3%) was most frequently detected among adults aged ≥19 years, and rhinovirus (23.4%) and adenovirus (23.6%) were predominant among young children aged 0–6 years. The remaining 5 viruses were detected at rates below 10% across all age groups (Figure 2).

Figure 1. Weekly detection status of respiratory virus during the 2023–2024 season

Figure 2. Detection status by age group of respiratory virus during the 2023–2024 season

Table 1 Number of respiratory viruses detected in the Republic of Korea

Seoson	Number of specimen	Detection rate (%)
		SARS-CoV-2	Rhino virus	Adeno virus	Boca virus	Metapneumo virus	Parainfluenza virus	Respiratory syncytial virus	Human corona virus	Influenza
2023–2024	18,040	15.1	14.9	9.9	3.2	4.2	5.6	5.0	3.8	15.1

SARS-CoV-2=severe acute respiratory syndrome coronavirus 2..

2. Detection Status of Influenza Viruses

Out of 18,040 specimens collected during the 2023–2024 season, 2,720 were positive for influenza viruses, resulting in an overall seasonal detection rate of 15.1%. The detection rates increased early in the season, peaked at 43.8% in week 50, then decreased, remaining below 2% from week 22 of 2024 onward. The predominant influenza subtype was A(H1N1)pdm09 (41.7%), followed by A(H3N2) (29.3%) and type B (29.1%), with all type B viruses belonging to the Victoria lineage (Table 2). Specifically, A(H1N1)pdm09 predominated until week 49 of 2023; from week 50 onwards, A(H3N2) became dominant alongside increased detections of type B. Beginning from week 1 of 2024, type B emerged as the predominant subtype (Figure 3).

Figure 3. Weekly detection status of influenza virus in the Republic of Korea during the 2023–2024 season

Table 2 Number of influenza viruses detected in the Republic of Korea

Seoson	Number of specimen	Detection rate (%)		Detection rate by subtype (%)
		Total		A(H1N1)pdm09	A(H3N2)	B
2023–2024	18,040	15.1		41.7	29.3	29.1

3. Characteristics of Influenza Viruses Circulating in the Republic of Korea

Genetic analyses of influenza viruses during the 2023–2024 season indicated that all circulating influenza subtypes—A(H1N1)pdm09, A(H3N2), and type B—belonged to genetic subclades highly similar to the vaccine strains (Table 3). For the predominant subtype A(H1N1)pdm09, two genetic subclades were detected: 6B.1A.5a.2a.1 (66.1%), which closely matched the vaccine strain 6B.1A.5a.2a.1, and 6B.1A.5a.2a (33.9%). The A(H3N2) subtype exclusively belonged to subclade 3C.2a1b.2a.3a.1, identical to the vaccine strain. All type B viruses were identified as that of the Victoria lineage, specifically subclade V1A.3a.2 (100.0%), matching the vaccine strain (Table 3).

Table 3 Analysis of influenza virus characteristics in the Republic of Korea during the 2023–2024 season

Virus	Clade of 2023–2024 season vaccine strain	Republic of Korea influenza virus in 2023–2024 season
		Genotype	Drug resistance	Antibody titera)
A(H1N1)pdm09	6B.1A.5a.2a.1	6B.1A.5a.2a (33.9%)	Sensitive	160–640
		6B.1A.5a.2a.1 (66.1%)
A(H3N2)	3C.2a1b.2a.2a	3C.2a1b.2a.2a.3a.1 (100.0%)	Sensitive	80–320
B(Victoria)	V1A.3a.2	V1A.3a.2 (100.0%)	Sensitive	80–320

^a)Neutralization capacity effective when the titer is over the 40..

To investigate potential antiviral-resistant influenza viruses, genetic sequencing of NA and PA genes and antiviral phenotypic analyses were conducted. No mutations associated with antiviral resistance were identified. Additionally, phenotypic assays directly exposing viruses to Oseltamivir, Zanamivir, and Peramivir confirmed that none exhibited antiviral resistance. Neutralization assays using antisera derived from ferrets immunized with vaccine strains (provided by WHO) demonstrated neutralizing antibody titers of ≥40 against all domestic influenza isolates tested (titers ranged from 160 to 640 for A(H1N1)pdm09 and from 80 to 320 for A(H3N2) and type B), confirming effective neutralization by the vaccine strain antisera.

An analysis of influenza and respiratory virus epidemiological trends and pathogen characteristics during the 2023–2024 season in ROK revealed a distinct pattern compared to the previous 2022–2023 season. Whereas influenza returned to typical seasonal epidemics dominated by subtype A(H3N2) (80.9%) in the 2022–2023 season, the 2023–2024 season initially showed simultaneous circulation of influenza A subtypes (A[H1N1]pdm09 and A[H3N2]), followed by an increased prevalence of type B viruses after week 48. Consequently, all three influenza virus subtypes—A(H1N1)pdm09, A(H3N2), and type B—circulated concurrently. Notably, influenza predominantly affected school-aged populations (7–18 years), highlighting communal living environments in schools and educational institutions as significant factors contributing to respiratory disease transmission [4].

Genetic characterization of influenza viruses circulating during the 2023–2024 season identified two genetic subclades for subtype A(H1N1)pdm09 (6B.1A.5a.2a and 6B.1A.5a.2a.1), a single genetic subclade for subtype A(H3N2) (3C.2a1b.2a.3a.1), and one genetic subclade for type B (Victoria lineage V1A.3a.2). All the identified subclades matched the vaccine strains selected for the 2023–2024 season, indicating high genetic homology. Furthermore, antigenic analyses confirmed that vaccine strain antisera effectively neutralized domestic influenza virus isolates. Therefore, it can be inferred that influenza vaccination during this season likely provided effective protection against infection. Genetic sequencing and antiviral phenotypic assays performed to assess antiviral drug resistance confirmed susceptibility to all tested antiviral agents, indicating the sustained efficacy of antiviral medications used to treat patients with influenza.

Among other respiratory viruses, the SARS-CoV-2 virus showed the highest detection rate at 15.1%, followed by rhinovirus (14.9%) and adenovirus (9.9%). The SARS-CoV-2 virus detection rates fluctuated throughout the season, but sharply increased during the summer months toward the latter part of the surveillance period, peaking at 43.5% in week 32 of 2024 and predominantly affecting adults aged ≥19 years. According to WHO surveillance data, global SARS-CoV-2 virus detections showed fluctuating trends from the latter half of 2023 to the first half of 2024, subsequently maintaining an increasing trend starting from week 25 of 2024 and peaking at 23.6% in week 35. This global epidemiological pattern closely mirrored the domestic detection trends [5]. Domestic adenovirus detection rates initially peaked at approximately 38% early in the season, then gradually declined from September onwards, returning to typical annual levels below 10% [6]. Similar trends were reported in the United States, with adenovirus detection rates also remaining below 10% [7].

The Division of Emerging Infectious Diseases at KDCA contributes to effective public health responses by monitoring key respiratory pathogens circulating in ROK, characterizing influenza viruses genetically and antigenically, and generating critical data to inform vaccine strain selection for subsequent seasons. Therefore, stable operation of the K-RISS and enhanced analysis of influenza and other respiratory viruses will continue to provide essential evidence for respiratory infection prevention and control in ROK, as well as support surveillance for the early detection of emerging respiratory pathogens, such as SARS-CoV-2.

Ethics Statement: Ethics approval for the study protocol and analysis of the data was obtained from the Institutional Review Board of the KDCA (2022-02-05-C-A).

Funding Source: This study was supported by intramural funds (grant no. 6300-6332-304) from the KDCA.

Acknowledgments: We thank 18 Public Health and Environment Research Institutes for support.

Conflict of Interest: Eun-Jin Kim is an editorial board member of the journal, but was not involved in the review process of this manuscript. Otherwise, there is no conflict of interest to declare.

Author Contributions: Conceptualization: SHW, NJL. Data curation: SHW, NJL, JHL. Formal analysis: SHW, NJL, JHL, JER, EJK. Investigation: SHW, NJL, JHL, JER, EJK. Project administration: NJL, JER, EJK. Supervision: JER, EJK. Visualization: SHW, NJL, JHL, JER, EJK. Writing – original draft: SHW. Writing – review & editing: JER, EJK.