1Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
2Vaccine Innovation Center-KU Medicine (VIC-K), Seoul, Korea
*Corresponding author: Joon Young Song,
Division of Infectious Diseases, Department of Internal Medicine, Korea
University Guro Hospital, Korea University College of Medicine, Gurodong-ro 148,
Guro-gu, Seoul 08308, Korea, E-mail:
infection@korea.ac.kr
• Received: May 18, 2024 • Revised: July 6, 2024 • Accepted: July 8, 2024
This is an Open-Access article distributed under the terms of the
Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits
unrestricted non-commercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Influenza presents a considerable disease burden, particularly among adults over
65 years old. In this population, the disease is associated with high rates of
infection, hospitalization, and mortality. The objective of this study was to
assess the impact of influenza on older adults and to evaluate the effectiveness
of influenza vaccines within this demographic. A literature search was conducted
using PubMed to identify relevant English-language studies published from
January 2000 to January 2024. The analysis indicated that influenza-related
hospitalization rates (ranging from 10.1 to 308.3 per 100,000 persons) and
all-cause excess mortality rates (1.1 to 228.2 per 100,000 persons) were notably
high in older adults, although these rates varied over time and by location.
Hospitalization rates due to influenza increased considerably after the age of
50 years, with the highest rates observed in individuals aged 85 years and
older. Excess mortality attributable to influenza also rose with age, with rates
between 17.9 and 223.5 per 100,000 persons in those over 75 years old. The
effectiveness of influenza vaccines in preventing severe infections requiring
hospitalization was found to be only 37% in individuals aged 65 years and older.
The unadjuvanted, standard-dose influenza vaccine had an estimated effectiveness
of just 25% against laboratory-confirmed influenza and between 37% and 43.7% in
preventing hospitalizations. Therefore, considering the substantial burden of
influenza and the limited efficacy of standard vaccines, the use of highly
immunogenic influenza vaccines should be prioritized for older adults.
Influenza accounts for the highest disease burden in terms of infection,
hospitalizations, and mortality rates among acute infectious diseases, leading to
high medical expenses and socioeconomic losses [1–3]. Each year, epidemics
affect more than 5% to 10% of the global population, with the extent of impact
varying based on the antigenic match of circulating strains and vaccination coverage
during the season [4]. A community-based
prospective cohort study from Korea reported an overall influenza incidence rate of
approximately 7 per 100 persons over three seasons from 2012 to 2015 [5]. The number of hospitalizations and deaths
from pneumonia and other complications surges following an influenza epidemic,
particularly affecting children under 5 years of age and adults over 65 years. Most
deaths occur in the latter population. Due to the consistently high impact of the
disease on older adults, a thorough review of the influenza disease burden and the
effectiveness of vaccines is crucial.
The objective of this narrative literature review was to evaluate the disease burden
of influenza, with a focus on its impact on older adults in terms of infection,
hospitalization, and mortality rates. Furthermore, this study aims to assess the
effectiveness of influenza vaccines in older adults across different seasons,
thereby providing insights that may improve vaccination strategies.
Ethics statement
It is a literature database-based review; therefore, neither approval by the
institutional review board nor obtainment of informed consent was required.
Methods
In this narrative literature review, we first conducted a search on PubMed for
relevant English-language articles, published between January 2000 and January 2024.
We employed the snowballing search method throughout the review process. The key
search terms included “influenza,” “influenza-like
illness,” “older adults,” “disease burden,”
“hospitalization,” “excess mortality,” efficacy,”
and “vaccine effectiveness,” which were tailored to each topic. After
reviewing titles, abstracts, and full manuscripts, we selected relevant studies for
inclusion in this review. Furthermore, we manually searched the references cited in
the chosen articles to identify additional sources pertinent to this review.
Results
Influenza-related hospitalizations in older adults
Influenza virus infections are more common among socially active young adults;
however, hospitalizations due to pneumonia and severe infections predominantly
affect older individuals, although rates vary across studies. Comparing
influenza-related hospitalization rates between countries is challenging due to
differences in the medical environment, including hospital accessibility and
admission criteria. A population-based study in the United States estimated
age-specific influenza-associated hospitalization rates for respiratory failure
(Table 1) [6]. The overall rate was 2.7 per 100,000 person-years, with
an increasing trend observed after the age of 50 years: 0.8 for ages
18–49; 4.0 for ages 50–64; 8.7 for ages 65–74; 16.5 for
ages 75–84; and 27.9 for those aged 85 and older. In a 15-year study
(1998–2012) in Hong Kong, an average of 32.7 per 10,000 persons were
hospitalized annually for respiratory viral infections, most commonly due to
influenza A (183 per 100,000 persons), respiratory syncytial virus (57 per
100,000 persons), and influenza B (35 per 100,000 persons). Hospitalizations
were particularly common among adults aged 65 years and over, with rates two to
three times higher than among those 50–64 years old [7]. In France, over eight epidemic seasons
from 2010/2011 to 2017/2018, the estimated influenza-associated excess
hospitalization rates ranged from 11.6 to 61.9 per 100,000 persons for influenza
and pneumonia and from 20.4 to 75.3 per 100,000 persons for respiratory causes
across all ages. For adults aged 65 years and over, the rates were 10.1 to 202.6
per 100,000 persons for influenza and pneumonia and 26.3 to 308.3 per 100,000
persons for respiratory causes [8]. A
Korean study utilizing a nationwide healthcare database (associated with the
Health Insurance Review and Assessment Service) over the decade from 2009 to
2019 found that the influenza-related hospitalization rate decreased following
the 2009 H1N1 pandemic but increased during the 2013/2014 season, peaking at
169.9 per 100,000 people in 2017/2018 [9].
Table 1.
Estimated rates of influenza-related hospitalization
Study [reference]
Years
Country
Category of admission
Annual rates of influenza-related
hospitalization (per 100,000 persons)
Influenza-attributable excess mortality among older adults
Using time series log-linear regression models based on vital death records and
influenza surveillance data, global seasonal influenza-associated respiratory
excess mortality rates were estimated for 33 countries. The results revealed an
increase in this rate with age. Influenza-associated excess mortality rates
ranged from 0.1 to 6.4 per 100,000 persons under 65 years, 2.9 to 44.0 per
100,000 persons between 65 and 74 years, and 17.9 to 223.5 per 100,000 persons
over 75 years (Table 2) [10]. These rates varied over time and by
location, influenced by factors such as age distribution, prevalence of chronic
diseases, dominant influenza subtype, population density, and climate.
Table 2.
Estimated excess mortality attributable to influenza
A study comparing the 2015/2016 and 2016/2017 influenza seasons across multiple
countries indicated that the all-cause excess mortality rates were 4.7 and 14.3
per 100,000 persons in the United States, 20.3 and 24.0 per 100,000 persons in
Denmark, and 22.9 and 52.9 per 100,000 persons in Spain, respectively [11]. The estimates for excess mortality due
to respiratory and circulatory causes were two to three times lower than those
for all causes. Another study in Denmark, spanning from 1994/1995 to 2009/2010,
reported a median all-cause excess mortality rate of 35 (range, 6–100)
per 100,000 persons; 88% of these deaths were among older adults aged 65 years
and above, with higher mortality observed during seasons dominated by the A/H3N2
subtype [12]. In Portugal, from 1980 to
2004, the estimated all-cause excess mortality rate was 24.7 per 100,000
persons, with approximately 90% of these deaths occurring in seniors over 65
years old [13]. Excess mortality rates
were three to six times higher during A/H3N2 subtype-dominant seasons compared
to those dominated by A/H1N1 or B viruses. Due to more rapid mutations and
antigenic drifts, A/H3N2 viruses likely pose a greater disease
burden—including higher hospitalization and mortality rates—than
A/H1N1 and B viruses [14]. In Italy,
three studies assessed nationwide excess deaths attributable to influenza
between 1970 and 2001 [15]. The findings
indicated influenza-related mortality rates of 1.9 to 2.2 per 100,000 persons
for pneumonia and influenza, while the all-cause rates were 11.6 to 18.6 per
100,000 persons. Among older adults, the age-adjusted excess death rates were
13.3 per 100,000 persons for pneumonia and influenza and 91.1 per 100,000
persons for all causes. In France, between the 2010/2011 and 2014/2015 seasons,
the all-cause influenza-associated excess mortality rates ranged from 0.3 to
26.6 per 100,000 persons for all ages and from 1.1 to 151.3 per 100,000 persons
for older adults aged 65 years and above [8].
Several Asian countries have reported comparatively high excess mortality rates,
with significant variations by country and season. A systematic review of 17
Chinese studies found that influenza-related excess mortality rates for all
causes, respiratory and circulatory diseases, and pneumonia/influenza varied
widely, with rates of 49.6–228.2, 30.8–170.2, and 0.7–30.4
per 100,000 persons, respectively [16].
Furthermore, Li et al. estimated the average annual influenza-associated excess
mortality rates by age group, revealing rates of 0.9, 66.1, and 519.6 per
100,000 persons for the age groups of 0–59 years, 60–79 years, and
≥80 years, respectively, between 2015 and 2018 [17]. In Korea, a nationwide matched cohort study indicated
an influenza-associated excess mortality rate of 49.5 per 100,000 persons, with
the highest rate observed in older adults aged ≥65 years [18]. Another Korean study, which combined
weekly mortality data from Statistics Korea with laboratory surveillance data
from the Korea Disease Control and Prevention Agency from 2009 to 2016,
estimated the all-cause excess mortality rate at 10.6 per 100,000 persons for
all ages and 74.1 per 100,000 persons for older adults [19]. In Japan, age-adjusted average excess mortality rates
were relatively low, averaging 6.2 per 100,000 persons during the 1970s and
1980s when vaccination of school-aged children was mandatory [20]. This rate increased to 9.4 per 100,000
persons in the 1990s upon discontinuation of the childhood vaccination program,
then decreased to 2.0 when influenza vaccination was administered to older
adults in the 2000s.
Low influenza vaccine effectiveness among older adults
Vaccination is recognized as 50% to 80% effective in preventing
laboratory-confirmed influenza among young adults [21]. However, a recent meta-analysis revealed that the
overall effectiveness of the influenza vaccine among older adults was only 25%,
with no statistically significant protection against influenza A/H3N2 in the
Northern Hemisphere [22]. Additionally,
the analysis indicated that pooled vaccine effectiveness diminished with
increasing age in both the Northern and Southern Hemispheres.
Most influenza-related hospitalizations and deaths occur among older adults.
Thus, the primary objective of influenza vaccination in this population is to
reduce the number of hospitalizations and deaths resulting from severe
infections. However, one meta-analysis indicated that the effectiveness of the
vaccine in preventing influenza-related hospitalization is only 43.7% (95% CI,
39.7%–47.4%) [23]. Another
meta-analysis, which stratified participants by age, indicated that the
influenza vaccine was 41% (95% CI, 34%–48%) effective in preventing
severe infections that required hospitalization among individuals aged
18–64 years and 37% (95% CI, 30%–44%) effective among those aged
65 years and older [24].
Recent studies have assessed the effectiveness of influenza vaccines in
preventing severe outcomes, such as organ failure and death. A study from the
United States conducted during the 2022–2023 season found the
effectiveness of vaccination against hospitalization due to type A influenza was
37% (95% CI, 27%–46%). This effectiveness varied by age group
(18–64 years: 47% [95% CI, 30%–60%]; ≥65 years: 28% [95%
CI, 10%–43%]) and by virus subtype (A/H3N2: 29% [95% CI, 6%–46%];
A/H1N1: 47% [95% CI, 23%–64%]) [25]. Additionally, the influenza vaccine was 65% (95% CI,
56%–72%) effective against influenza-related organ failure (involving the
respiratory, cardiovascular, or renal systems) and 48% (95% CI, −70% to
84%) effective against death. In a separate study from Norway covering the same
season, the effectiveness of vaccination against influenza-associated
hospitalization was 34% (95% CI, 26%–42%) for adults aged 65–79
years and 40% (95% CI, 30%–48%) for individuals aged ≥80 years.
The effectiveness against influenza-associated death was 6.6% (95% CI,
−64% to 47%) for the 65–79 age group and 37% (95% CI,
0.5%–61%) for those aged ≥80 years [26]. While the influenza vaccine does reduce the risk of
severe disease, its effectiveness is considerably lower than that of the
vaccines for coronavirus disease 2019 (COVID-19). For preventing
COVID-19–associated hospitalization, the effectiveness of vaccination was
65% (95% CI, 61%–69%) among adults aged 65–79 years and 55% (95%
CI, 49%–60%) among those aged ≥80 years [26]. Regarding COVID-19–associated death, the
effectiveness was 68% (95% CI, 48%–80%) for the 65–79 age group
and 78% (95% CI, 65%–86%) for those aged ≥80 years.
Discussion
Given the high rates of hospitalization and death among older adults, reducing the
disease burden of influenza through vaccination is essential. In Korea, the
vaccination rate for seniors aged 65 years and older has been maintained at over 80%
[27]. However, the antibody titer
produced in older adult populations following influenza vaccination is approximately
40% to 80% of that in healthy adults, indicating relatively low vaccine
effectiveness, ranging from 31% to 58% [28,29].
Influenza vaccines are currently approved based on a hemagglutination inhibition (HI)
antibody titer of ≥40 for young adults under 60 years old and ≥30 for
seniors over 60 years. However, an HI titer of 1:30 or 1:40 only represents the
antibody level that can prevent 50% of influenza virus infections in healthy adults
[30]. To achieve vaccine effectiveness
greater than 90%, an HI titer exceeding 1:100 may be necessary; however, it is
challenging to attain such high immunogenicity among older adults with available
conventional vaccines [30]. Furthermore,
since seasonal influenza epidemics can persist for more than 6 months, maintaining
adequate protective immunity over this duration is crucial. However, HI titers
typically start to wane after vaccination and decline sharply after 6 months [31]. The lower vaccine effectiveness observed
in older adults aged 65 years and older may also stem from the short duration of
vaccine-induced immunity and immune imprinting from repeated exposure, particularly
to influenza A/H3N2. Consequently, a need exists for influenza vaccines that are
highly immunogenic, induce long-lasting immunity, and minimize immune imprinting. To
increase the efficacy of influenza vaccines in older adults, high-dose (Fluzone
High-Dose, 60 μg hemagglutinin [HA]/strain), MF59-adjuvanted (Fluad, 15
μg HA/strain), and intradermal (Fluzone Intradermal, 15 μg HA/strain)
vaccines have been developed [32-34]. Compared to the conventional standard-dose
vaccine, these options have demonstrated higher immunogenicity in terms of their
relative HI titer ratios [35]. Although
intradermal vaccines are no longer produced, both MF59-adjuvanted and high-dose
vaccines have been introduced and are currently available for use.
When evaluating the relative vaccine effectiveness of the MF59-adjuvanted influenza
vaccine compared to the unadjuvanted standard-dose vaccine over three consecutive
influenza seasons (2017–2018, 2018–2019, and 2019–2020) in the
United States, the MF59-adjuvanted, trivalent vaccine displayed superior
effectiveness over the quadrivalent alternative. The MF59-adjuvanted option
displayed better prevention of influenza-related medical visits, with relative
effectiveness estimates ranging from 20.8% (95% CI, 18.4%–23.2%) to 27.5%
(95% CI, 24.4%–30.5%) [36].
Additionally, the MF59-adjuvanted trivalent influenza vaccine further reduced
influenza-related hospitalizations, demonstrating a relative vaccine effectiveness
of 6.5% (95% CI, 0.1%–12.4%). In a meta-analysis comparing the relative
effectiveness of high-dose versus standard-dose, unadjuvanted influenza vaccines,
the high-dose option displayed superior protection against influenza-like illness
compared to the standard-dose vaccine, with a relative effectiveness of 15.9% (95%
CI, 4.1%–26.3%) [37]. Moreover, the
high-dose vaccine was more effective in preventing hospital admissions, with
significant relative effectiveness against all causes (8.4%; 95% CI,
5.7%–11.0%), pneumonia/influenza (13.4%; 95% CI, 7.3%–19.2%), and
cardiorespiratory events (17.9%; 95% CI, 15.0%–20.8%). When the relative
effectiveness of the MF59-adjuvanted vaccine was compared to the high-dose vaccine
in a meta-analysis that excluded studies sponsored by pharmaceutical companies, no
significant difference was found in the prevention of influenza-related emergency
room visits, hospitalizations, or pneumonia between the two vaccines [29].
Antigenic mismatches between newly developed vaccines and circulating strains can
meaningfully reduce vaccine efficacy. In a randomized study, the MF59-adjuvanted
influenza vaccine demonstrated greater cross-reactivity against antigenically
drifted, heterovariant A/H3N2 strains compared to the unadjuvanted standard-dose
influenza vaccine [14]. Further research is
required to ascertain whether the MF59-adjuvanted or the high-dose influenza vaccine
is more advantageous in terms of immunological outcomes, including cross-reactive
immunity to variant viruses and the capacity to overcome immune imprinting.
In conclusion, influenza imposes a considerable disease burden on older adults,
characterized by high rates of infection, hospitalization, and mortality. The
effectiveness of influenza vaccines in this demographic fluctuates by season but is
substantially lower than that observed in younger adults. Even with high vaccination
rates among older adults, the suboptimal effectiveness underscores the need for
improved vaccination strategies. These include the use of high-dose and adjuvanted
vaccines to increase immunogenicity and afford more robust protection against
influenza in this vulnerable age group.
Authors' contributions
All work was done by Joon Young Song.
Conflict of interest
No potential conflict of interest relevant to this article was reported.
Funding
Not applicable.
Data availability
Not applicable.
Acknowledgments
Not applicable.
Supplementary materials
Not applicable.
References
1. Yang TU, Song JY, Noh JY, Cheong HJ, Kim WJ. Influenza and pneumococcal vaccine coverage rates among patients
admitted to a teaching hospital in South Korea. Infect Chemother 2015;47(1):41-48.
2. Cassini A, Colzani E, Pini A, Mangen MJJ, Plass D, McDonald SA, et al. Impact of infectious diseases on population health using
incidence-based disability-adjusted life years (DALYs): results from the
Burden of Communicable Diseases in Europe study, European Union and European
Economic Area countries, 2009 to 2013. Eur Surveill 2018;23(16):17-00454.
3. Kang SH, Cheong HJ, Song JY, Noh JY, Jeon JH, Choi MJ, et al. Analysis of risk factors for severe acute respiratory infection
and pneumonia and among adult patients with acute respiratory illness during
2011-2014 influenza seasons in Korea. Infect Chemother 2016;48(4):294-301.
4. Fischer WA 2nd, Gong M, Bhagwanjee S, Sevransky J. Global burden of influenza as a cause of cardiopulmonary
morbidity and mortality. Glob Heart 2014;9(3):325-336.
5. Chun BC. Epidemiology and surveillance of influenza. In: Kim WJ, editor. Influenza. Seoul: Transgovernmental Enterprise for Pandemic Influenza in Korea
(TEPIK); 2016.
6. Ortiz JR, Neuzil KM, Rue TC, Zhou H, Shay DK, Cheng PY, et al. Population-based incidence estimates of influenza-associated
respiratory failure hospitalizations, 2003 to 2009. Am J Respir Crit Care Med 2013;188(6):710-715.
7. Chan PKS, Tam WWS, Lee TC, Hon KL, Lee N, Chan MCW, et al. Hospitalization incidence, mortality, and seasonality of common
respiratory viruses over a period of 15 years in a developed subtropical
city. Medicine 2015;94(46):e2024.
8. Lemaitre M, Fouad F, Carrat F, Crépey P, Gaillat J, Gavazzi G, et al. Estimating the burden of influenza-related and associated
hospitalizations and deaths in France: an eight-season data study,
2010–2018. Influenza Other Respir Viruses 2022;16(4):717-725.
9. Hong TH, Lee HS, Kim NE, Lee KJ, Kim YK, An JN, et al. Recent increases in influenza-related hospitalizations, critical
care resource use, and in-hospital mortality: a 10-year population-based
study in South Korea. J Clin Med 2022;11(16):4911
11. Schmidt SSS, Iuliano AD, Vestergaard LS, Mazagatos-Ateca C, Larrauri A, Brauner JM, et al. All-cause versus cause-specific excess deaths for estimating
influenza-associated mortality in Denmark, Spain, and the United
States. Influenza Other Respir Viruses 2022;16(4):707-716.
12. Nielsen J, Mazick A, Glismann S, Mølbak K. Excess mortality related to seasonal influenza and extreme
temperatures in Denmark, 1994-2010. BMC Infect Dis 2011;11:350
13. Nunes B, Viboud C, Machado A, Ringholz C, Rebelo-de-Andrade H, Nogueira P, et al. Excess mortality associated with influenza epidemics in Portugal,
1980 to 2004. PLoS One 2011;6(6):e20661.
15. Giacchetta I, Primieri C, Cavalieri R, Domnich A, de Waure C. The burden of seasonal influenza in Italy: a systematic review of
influenza-related complications, hospitalizations, and
mortality. Influenza Other Respir Viruses 2021;16(2):351-365.
16. Li S, Liu SS, Zhu AQ, Cui JZ, Qin Y, Zheng JD, et al. The mortality burden of influenza in China: a systematic
review. Zhonghua Yu Fang Yi Xue Za Zhi 2019;53(10):1049-1055.
17. Li L, Yan ZL, Luo L, Liu W, Yang Z, Shi C, et al. Influenza-associated excess mortality by age, sex, and
subtype/lineage: population-based time-series study with a distributed-lag
nonlinear model. JMIR Public Health Surveill 2023;9:e42530.
18. Jang H, Cho J, Cho SK, Lee D, Cho S, Koh SB, et al. All-cause and cause-specific mortality attributable to seasonal
influenza: a nationwide matched cohort study. J Korean Med Sci 2023;38(25):e188.
20. Ohmi K, Marui E. Estimation of the excess death associated with influenza
pandemics and epidemics in Japan after world war II: relation with pandemics
and the vaccination system. Nihon Koshu Eisei Zasshi 2011;58(10):867-878.
22. Okoli GN, Racovitan F, Abdulwahid T, Righolt CH, Mahmud SM. Variable seasonal influenza vaccine effectiveness across
geographical regions, age groups and levels of vaccine antigenic similarity
with circulating virus strains: a systematic review and meta-analysis of the
evidence from test-negative design studies after the 2009/10 influenza
pandemic. Vaccine 2021;39(8):1225-1240.
23. Guo J, Chen X, Guo Y, Liu M, Li P, Tao Y, et al. Real-world effectiveness of seasonal influenza vaccination and
age as effect modifier: a systematic review, meta-analysis and
meta-regression of test-negative design studies. Vaccine 2024;42(8):1883-1891.
24. Rondy M, El Omeiri N, Thompson MG, Levêque A, Moren A, Sullivan SG. Effectiveness of influenza vaccines in preventing severe
influenza illness among adults: a systematic review and meta-analysis of
test-negative design case-control studies. J Infect 2017;75(5):381-394.
25. Lewis NM, Zhu Y, Peltan ID, Gaglani M, McNeal T, Ghamande S, et al. Vaccine effectiveness against influenza A–associated
hospitalization, organ failure, and death: United States,
2022–2023. Clin Infect Dis 2024;78(4):1056-1064.
26. Seppälä E, Dahl J, Veneti L, Rydland KM, Klüwer B, Rohringer A, et al. COVID-19 and influenza vaccine effectiveness against associated
hospital admission and death among individuals over 65 years in Norway: a
population-based cohort study, 3 October 2022 to 20 June
2023. Vaccine 2024;42(3):620-628.
27. Yun JW, Noh JY, Song JY, Chun C, Kim Y, Cheong HJ. The Korean influenza national immunization program: history and
present status. Infect Chemother 2017;49(4):247-254.
28. Seidman JC, Richard SA, Viboud C, Miller MA. Quantitative review of antibody response to inactivated seasonal
influenza vaccines. Influenza Other Respir Viruses 2011;6(1):52-62.
29. Domnich A, de Waure C. Comparative effectiveness of adjuvanted versus high-dose seasonal
influenza vaccines for older adults: a systematic review and
meta-analysis. Int J Infect Dis 2022;122:855-863.
30. Coudeville L, Bailleux F, Riche B, Megas F, Andre P, Ecochard R. Relationship between haemagglutination-inhibiting antibody titres
and clinical protection against influenza: development and application of a
Bayesian random-effects model. BMC Med Res Methodol 2010;10:18
31. Song JY, Cheong HJ, Hwang IS, Choi WS, Jo YM, Park DW, et al. Long-term immunogenicity of influenza vaccine among the elderly:
risk factors for poor immune response and persistence. Vaccine 2010;28(23):3929-3935.
33. Choi WS, Song JY, Kwon KT, Lee HJ, Choo EJ, Baek J, et al. Recommendations for adult immunization by the Korean Society of
Infectious Diseases, 2023: minor revisions to the 3rd
edition. Infect Chemother 2024;56(2):188-203.
36. Boikos C, McGovern I, Ortiz JR, Puig-Barberà J, Versage E, Haag M. Relative vaccine effectiveness of adjuvanted trivalent influenza
vaccine over three consecutive influenza seasons in the United
States. Vaccines 2022;10(9):1456
37. Lee JKH, Lam GKL, Shin T, Samson SI, Greenberg DP, Chit A. Efficacy and effectiveness of high-dose influenza vaccine in
older adults by circulating strain and antigenic match: an updated
systematic review and meta-analysis. Vaccine 2021;39(Suppl 1):A24-A35.
Unresolved policy on the new placement of 2,000 entrants at Korean
medical schools and this issue of Ewha Medical
Journal Sun Huh The Ewha Medical Journal.2024;[Epub] CrossRef
