Respiratory syncytial virus infection and the need for immunization in Korea

Figures & data

Table 1. Prevalence and detection rate of respiratory syncytial virus among children hospitalized with acute respiratory tract infections in Korea.

Study	Period	Age	Reason for hospitalization	Diagnostic test method	Total N/Confirmed viral etiology N	Prevalence of RSV in patients with acute RTI (%)	RSV detection rate in patients with positive viral samples (%)	Other results
Yun et al. 1995 [58]	Nov 1990–Apr 1994	2 weeks-14.4 years (median 9 months)	Acute LRTI	VC, IF	712/369	27.2	59.3	85% of RSV patients were <2 years
Ahn et al. 1999 [59]	Mar 1996–Feb 1998	≤15 years	Acute LRTI	IF	1070/237	–	21.5	RSV predominantly isolated in infants aged ≤1 year; no cases seen in children aged >5 years
Kim et al. 2000 [60]	Jan 1994 – Aug 1998	1 month – 10.75 years (RSV: mean 11.4 ± 4.6 months)	Acute RTI	IF	1389/360	–	41.8^a	69.9% of RSV cases were aged <1 year
Choi et al. 2006 [61]	Sep 2000–Aug 2005	≤5 years	Acute LRTI	RT-PCR	515/312	23.7	39.1^b	RSV accounted for 77% of LRTIs in infants aged ≤3 months
Chung et al. 2007 [71]	Feb–Nov 2006	≤5 years	Acute wheezing	IF	231/142	13.8	22.5^b	Among RSV cases, 71.9% were aged <1 year, 28.1% were aged 1 to <3 years and none were ≥3 years
Kim et al. 2008 [62]	Mar 2004–Dec 2005	<15 years	LRTI	VC, RAD	400/na	–	48	RSV most common at age <2 years (almost twice as common vs children aged 2 years)
Chun et al. 2009 [63]	Nov 2007–Apr 2008	<5 years (RSV: median 13 months, range 2–66)	Acute LRTI	RT-PCR, VC	296/147	29.4^b	52.7
Kim et al. 2010 [72]	Dec 2003–Apr 2008	1–150 months (RSV: mean 15 ± 27 months)	Acute RTI-wheezing illness	IF	1008/na	26.0	–	82.2% of RSV-positive patients were diagnosed with wheezing illness. RSV more common than HMPV at age <12 years (p < 0.05)
Baek et al. 2012 [64]	Oct 2008–Feb 2010	90 days–6 years	Respiratory illness	RT-PCR	965/na	30.8	–	60% of RSV cases were aged <2 years. Among RSV-positive samples, 67% were RSV-A, 33% were RSV-B
Seo et al. 2014 [65]	Jan 2005–Dec 2008	<19 years	Acute RTI	VC, IF	21,641^c/5257^c	7.3	30.0^b
Cho et al. 2013 [66]	Jan 2009–May 2010	<1 month	Acute LRTI	RT-PCR	140/108	–	42.6	Detection rate for RSV-A 26.9%, RSV-B 15.7%
Kwon et al. 2014 [67]	May 2010–Apr 2011	Median 26 months (IQR 16–39)	Acute LRTI	RT-PCR	309/309^d	–	34.9	Mean age of RSV cases was 23 ± 20 months. RSV was present in 57.6% of bronchiolitis cases
Seo et al. 2014 [68]	Jul 2009–Apr 2012	<15 years	Acute febrile respiratory illness	RT-PCR	3865^c/2800^c	–	RSV-A 17.4% RSV-B 11.7%
Lee et al. 2015 [73]	Apr 2009–Mar 2010	Preterm infants (GA 22–32 weeks) discharged from neonatal ICU	Readmission for respiratory problems	Not specified	431/na	16.2	30.3^a	Among infants who attended the emergency room with respiratory problems, 9.8% were diagnosed with RSV infection, and RSV accounted for 32.4% of laboratory-detected viruses
Choi et al. 2018 [69]	Jan 2013–Dec 2015	<15 years	Acute RTI	RT-PCR	2424/2424^d	–	RSV-A 17.0^e RSV-B 12.1^e	RSV was the most common pathogen in infants <1 year old
Lee et al. 2020 [70]	Jan 2010–Dec 2015	<18 years	CAP	RT-PCR	30,994/30,994 ^f	20.3	–	RSV was detected in 34.0% of children aged <2 years (most common pathogen in this age group). 2.6% of RSV pneumonia cases required ICU admission

a Detection rate amongst total number of viral isolates identified.

b Estimated based on data in the associated publication.

c Number of respiratory samples (patients may have had more than one sample collected).

d Only patients with a confirmed virologic cause were included in the analysis.

e Among single-virus cases.

f Patients with a confirmed virologic/bacteriologic cause were included in the analysis.

CAP = community-acquired pneumonia; GA = gestational age; HMPV = human metapneumovirus; ICU = intensive care unit; IQR = interquartile range; IF = immunofluorescent staining; LRTI = lower respiratory tract infection; N = number; na = not available; RAD = rapid antigen detection; RSV = respiratory syncytial virus; RTI = respiratory tract infection; RT-PCR = reverse transcription-polymerase chain reaction; VC, viral culture; wks = weeks

Table 2. Prevalence and detection rate of respiratory syncytial virus among adults hospitalized with acute respiratory tract infections in Korea.

Study	Period	Age	Reason for hospitalization	Diagnostic test method	Total N/Confirmed viral etiology N	Prevalence of RSV in patients with acute RTI (%)	RSV detection rate in patients with positive viral samples (%)	Other results
Seo et al. 2014 [65]	Jan 2005–Dec 2008	≥19 years	Acute RTI	VC, IF	2165^a/255^a	1.1	9.0^b
Seo et al. 2014 [68]	Jul 2009–Apr 2012	>19 years (53.9% ≥65 years)	Acute febrile respiratory illness	RT-PCR	763^a/205^a	–	RSV-A ~ 4^b RSV-B ~ 3^b
Kwon et al. 2017 [67]	Jan 2013–Dec 2015	≥18 years (mean 70 ± 12 years)	Suspected respiratory viral infection	RT-PCR	3743/–	2.3	–	20-day mortality in RSV patients 18.4% (adjusted hazard ratio vs influenza 2.32, 95% CI 1.17–4.58)
Noh et al. 2013 [88]	Sep 2011–Jun 2012	≥18 years (median 43 years, IQR 31–63; 23.2% ≥65 years)	Influenza-like illness^c	RT-PCR	1983/1100^d	–	2.8^d
Choi et al. 2012 [89]	Mar 2010–Feb 2011	≥18 years (mean 65.4 years, range 17–96)	Severe CAP^e or severe HCAP^e	RT-PCR	198/72	5.1 RSV-A 2.0 RSV-B 3.0	13.9	RSV more common in CAP than HCAP (10.9% vs 2.2% patients, p = 0.01). RSV-associated mortality 20.0%
Hong et al. 2014 [90]	Mar 2010–Feb 2012	Mean age 64.5 ± 13.5 years	Severe HAP^e	RT-PCR	262/59	6.1 RSV-A 4.2 RSV-B 1.9	27.1 RSV-A 18.6 RSV-B 8.5	Median 20 days’ hospitalization prior to pneumonia diagnosis. RSV-associated mortality 37.5%
Kim et al. 2018 [91]	Jan 2008–Dec 2015	Median 64 years (IQR 56–73)	Severe CAP^e, severe HCAP^e or severe HAP^e	RT-PCR	515/69	RSV-A 4.1 RSV-B 1.8	–

a Number of respiratory samples (patients may have had more than one sample collected).

b Estimated from data/graph in the associated publication.

c Requiring emergency room visit.

d Total number of detected viruses (1100). RSV detection rate among total number of viral isolates detected is reported.

e Requiring ICU admission.

CAP = community-acquired pneumonia; CI = confidence interval; HAP = hospital-associated pneumonia; HCAP = healthcare-associated pneumonia; ICU = intensive care unit; IF = immunofluorescent staining; IQR = interquartile range;; N = number; RSV = respiratory syncytial virus; RT-PCR = reverse transcription-polymerase chain reaction; RTI = respiratory tract infection; VC = viral culture.

Table 3. Data relevant to quantifying burden of disease associated with RSV in Korea.

Outcome	Available data
PEDIATRIC POPULATION
Incidence/Prevalence
RSV rate among children hospitalized with acute RTI	- 7.3–30.8% [58–70]
Proportion of neonatal ICU admissions due to viral LRTI caused by RSV among previously healthy neonates	- 13.8% [66]
RSV-associated hospitalization by age	- Most common in children aged <2 years; around 70% of hospitalized RSV cases aged <1 year [58–62,64,69,70]
RSV-related admissions to pediatric ICU by age	- 75% aged <2 years and 48.9% aged <6 months [74]
Risk factors
Prematurity	- Among preterm infants (born gestational age 22–32 weeks) later readmitted to hospital for any reason, 3% had RSV infection (16.2% among those who had respiratory problems) [73] - 4.5% of preterm infants (born gestational age <35 weeks; no chronic lung disease; no palivizumab prophylaxis) readmitted to hospital with suspected RSV infection during the first year after initial discharge from neonatal ICU [75] - 8.4% of preterm infants (born gestational age <34 weeks) readmitted to hospital with an RSV infection within 1 year of discharge from neonatal ICU (3.3% after palivizumab prophylaxis; 41.4% no prophylaxis) [76]
Bronchopulmonary dysplasia	- RSV hospitalization rate 5.2% [77] or 22.6% [78] with no palivizumab prophylaxis and 0.7% or 4.0%, respectively, with prophylaxis - RSV hospitalization rate 8.9% among infants with history of very low birthweight and BPD (and aged <2 years at start of RSV season) who received prophylaxis [79]
Congenital heart disease	- Prior to the palivizumab era, 48.9% of CHD patients hospitalized with RSV-LRTI required ICU care versus 9.7% of non-CHD patients [80] - After palivizumab prophylaxis, 12.2% of CHD patients were hospitalized with RSV-associated bronchiolitis, and 24.6% of the hospitalized patients required ICU admission [81]
Medical resources/Costs
Length of hospital stay	- Among neonates admitted to neonatal ICU with LRTI, RSV was associated with longer hospital stay versus other viral causes (9.41 versus 7.34 days, p = 0.011) [66]
Healthcare cost	- For children aged <2 years admitted to the pediatric ICU with RSV infection, median cost US$1,899 (range 556–30,449) for those not considered high-risk and US$2,284 (range 705–98,243) for high-risk patients [including median US$1,866 for those with chronic lung disease, US$3,730 for those with congenital heart disease and US$9,929 for those with neuromuscular disorder/congenital abnormality of airway]) (years 2008–2013) [74]
ADULT POPULATION
Incidence/Prevalence
RSV rate among adults hospitalized with acute RTIs	- 1.1% (mean/median age of study population not reported) [65]
RSV rate among adults hospitalized with suspected viral RTIs	- 2.3% (mean age of study population 70 years) [87]
RSV rate among adults attending emergency room with influenza-like illness	- RSV accounted for 2.8% of viruses detected (median age of study population 43 years) [88]
RSV rate among adults with severe pneumonia admitted to ICU	- 5.1–6.9% (mean/median age of study population 65 years) [89–91]
RSV-associated hospitalization by age	- 64.7% were aged ≥65 years; ICU admission rate higher for age ≥65 years (25%) versus 50–64 years (11.5%) or 19–49 years (10.0%); need for mechanical ventilation also higher (11.4% versus 5.8% versus 0%) (both p = NS) [93]
Mortality
Adults with RSV attending emergency room	- Median age 65 years (range 19–99); 15% had life-threatening infection; in-hospital mortality 7.9% [30]
Hospitalized adults with RSV infection	- In-hospital mortality 13.6% (adults with RSV pneumonia) [93] - 20-day mortality 18.4% (significantly higher than with influenza; hazard ratio 2.32, 95% CI 1.17–4.58) [87]
Risk factors
Older age	- Among adults hospitalized with RSV infection mean age was 70 years (significantly higher than for influenza patients) [87]
Comorbidities	- Among adults hospitalized with acute RSV infection, 75–80% had comorbidities [68] - Among adults hospitalized with RSV infection, 12.6% had chronic obstructive pulmonary disease (significantly higher than influenza patients) [87] - Among inpatients of any age with respiratory symptoms, the rate of co-infection with RSV plus other viruses was highest in those aged >80 years (80%) [55]
Medical resources/Costs
Length of hospital stay	- Mean 16.1 days among adults hospitalized with RSV-A–associated acute RTI (median age 71 years) [68] - Mean 19.4 days among adults hospitalized with RSV pneumonia; mean 20.4 days for those aged >65 years (versus 17–19 days for younger age groups) [93]
Rate of ICU admission among adults hospitalized with RSV pneumonia	- 20% among adults hospitalized with RSV-A–associated acute RTI [68] - 22% among all adults hospitalized with RSV pneumonia; 26.7% among those aged >65 years (versus 8.3–16.1% for younger age groups) [93]
Healthcare costs	- Median medical cost per adult RSV pneumonia hospital admission US$2,855; median US$2,933 for patients aged >65 years (versus US$1,957–2,116 for younger age groups) (years 2012–2015) [93]

BPD = bronchopulmonary dysplasia; CHD = congenital heart disease; CI = confidence interval; ICU = intensive care unit; LRTI = lower respiratory tract infection; NS = not significant; RSV = respiratory syncytial virus; RTI = respiratory tract infection.

Yun BY, Kim MR, Park JY, et al. Viral etiology and epidemiology of acute lower respiratory tract infections in Korean children. Pediatr Infect Dis J. 1995;14(12):1054–1059.

 PubMed Web of Science ®Google Scholar

Ahn KM, Chung SH, Chung EH, et al. Clinical characteristics of acute viral lower respiratory tract infections in hospitalized children in Seoul, 1996-1998. J Korean Med Sci. 1999;14(4):405–411.

 PubMed Web of Science ®Google Scholar

Kim MR, Lee HR, Lee GM. Epidemiology of acute viral respiratory tract infections in Korean children. J Infect. 2000;41(2):152–158.

 PubMed Web of Science ®Google Scholar

Choi EH, Lee HJ, Kim SJ, et al. The association of newly identified respiratory viruses with lower respiratory tract infections in Korean children, 2000-2005. Clin Infect Dis. 2006;43(5):585–592.

 PubMed Web of Science ®Google Scholar

Chung JY, Han TH, Kim SW, et al. Detection of viruses identified recently in children with acute wheezing. J Med Virol. 2007;79(8):1238–1243.

 PubMed Web of Science ®Google Scholar

Kim YK, Nyambat B, Hong YS, et al. Burden of viral respiratory disease hospitalizations among children in a community of Seoul, Republic of Korea, 1995-2005. Scand J Infect Dis. 2008;40(11–12):946–953.

 PubMed Web of Science ®Google Scholar

Chun JK, Lee JH, Kim HS, et al. Establishing a surveillance network for severe lower respiratory tract infections in Korean infants and young children. Eur J Clin Microbiol Infect Dis. 2009;28(7):841–844.

 PubMed Web of Science ®Google Scholar

Kim CK, Choi J, Callaway Z, et al. Clinical and epidemiological comparison of human metapneumovirus and respiratory syncytial virus in Seoul, Korea, 2003-2008. J Korean Med Sci. 2010;25(3):342–347.

 PubMed Web of Science ®Google Scholar

Baek YH, Choi EH, Song MS, et al. Prevalence and genetic characterization of respiratory syncytial virus (RSV) in hospitalized children in Korea. Arch Virol. 2012;157(6):1039–1050.

 PubMed Web of Science ®Google Scholar

Seo YB, Cheong HJ, Song JY, et al. Epidemiologic differences of four major respiratory viruses between children, adolescents, and adults in Korea. J Infect Chemother. 2014;20(11):672–677.

 PubMed Web of Science ®Google Scholar

Cho HJ, Shim SY, Son DW, et al. Respiratory viruses in neonates hospitalized with acute lower respiratory tract infections. Pediatr Int. 2013;55(1):49–53.

 PubMed Web of Science ®Google Scholar

Kwon JM, Shim JW, Kim DS, et al. Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations. Korean J Pediatr. 2014;57(1):29–34.

 PubMedGoogle Scholar

Seo YB, Song JY, Choi MJ, et al. Etiology and clinical outcomes of acute respiratory virus infection in hospitalized adults. Infect Chemother. 2014;46(2):67–76.

 PubMedGoogle Scholar

Lee JH, Chang YS, Committee on Data Collection and Statistical Analysis, the Korean Society of Neonatology. Use of medical resources by preterm infants born at less than 33 weeks’ gestation following discharge from the neonatal intensive care unit in Korea. J Korean Med Sci. 2015;30(Suppl 1):S95–S103.

 PubMedGoogle Scholar

Choi E, Ha KS, Song DJ, et al. Clinical and laboratory profiles of hospitalized children with acute respiratory virus infection. Korean J Pediatr. 2018;61(6):180–186.

 PubMedGoogle Scholar

Lee E, Kim CH, Lee YJ, et al. Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea. BMC Infect Dis. 2020;20(1):132.

 PubMed Web of Science ®Google Scholar

Noh JY, Song JY, Cheong HJ, et al. Laboratory surveillance of influenza-like illness in seven teaching hospitals, South Korea: 2011-2012 season. PLoS One. 2013;8(5):e64295.

 PubMed Web of Science ®Google Scholar

Choi SH, Hong SB, Ko GB, et al. Viral infection in patients with severe pneumonia requiring intensive care unit admission. Am J Respir Crit Care Med. 2012;186(4):325–332.

 PubMed Web of Science ®Google Scholar

Hong HL, Hong SB, Ko GB, et al. Viral infection is not uncommon in adult patients with severe hospital-acquired pneumonia. PLoS One. 2014;9(4):e95865.

 PubMed Web of Science ®Google Scholar

Kim HJ, Choi SM, Lee J, et al. Respiratory virus of severe pneumonia in South Korea: prevalence and clinical implications. PLoS One. 2018;13(6):e0198902.

 PubMed Web of Science ®Google Scholar

Kang JM, Lee J, Kim YK, et al. Pediatric intensive care unit admission due to respiratory syncytial virus: retrospective multicenter study. Pediatr Int. 2019;61(7):688–696.

 PubMed Web of Science ®Google Scholar

Park HW, Lee BS, Kim AR, et al. Epidemiology of respiratory syncytial virus infection in infants born at less than thirty-five weeks of gestational age. Pediatr Infect Dis J. 2012;31(8):e99–104.

 PubMed Web of Science ®Google Scholar

Lee JH, Kim CS, Chang YS, et al. Respiratory syncytial virus related readmission in preterm infants less than 34 weeks’ gestation following discharge from a neonatal intensive care unit in Korea. J Korean Med Sci. 2015;30(Suppl1):S104–S110.

 PubMedGoogle Scholar

Park SK, Jung YJ, Yoo HS, et al. Effect of Synagis® (palivizumab) prophylaxis on readmission due to respiratory syncytial virus in very low birth weight infants. Korean J Pediatr. 2010;53(3):358–363.

 Google Scholar

Chang SG, Park MS, Yu JE. Outcomes of palivizumab prophylaxis for respiratory syncytial virus infection in preterm children with bronchopulmonary dysplasia at a single hospital in Korea from 2005 to 2009. J Korean Med Sci. 2010;25(2):251–256.

 PubMed Web of Science ®Google Scholar

Han YM, Seo HJ, Choi SH, et al. Effect of prophylactic palivizumab on admission due to respiratory syncytial virus infection in former very low birth weight infants with bronchopulmonary dysplasia. J Korean Med Sci. 2015;30(7):924–931.

 PubMed Web of Science ®Google Scholar

Shim WS, Lee JY, Song JY, et al. Respiratory syncytial virus infection cases in congenital heart disease patients. Korean J Pediatr. 2010;53(3):380–391.

 Google Scholar

Kim AY, Jung SY, Choi JY, et al. Retrospective multicenter study of respiratory syncytial virus prophylaxis in Korean children with congenital heart diseases. Korean Circ J. 2016;46(5):719–726.

 PubMed Web of Science ®Google Scholar

Kwon YS, Park SH, Kim MA, et al. Risk of mortality associated with respiratory syncytial virus and influenza infection in adults. BMC Infect Dis. 2017;17(1):785.

 PubMedGoogle Scholar

Yoon JG, Noh JY, Choi WS, et al. Clinical characteristics and disease burden of respiratory syncytial virus infection among hospitalized adults. Sci Rep. 2020;10(1):12106.

 PubMed Web of Science ®Google Scholar

Park SY, Kim T, Jang YR, et al. Factors predicting life-threatening infections with respiratory syncytial virus in adult patients. Infect Dis (Lond). 2017;49(5):333–340.

 PubMed Web of Science ®Google Scholar

Kim GY, Rheem I, Joung YH, et al. Investigation of occurrence patterns of respiratory syncytial virus A and B in infected-patients from Cheonan, Korea. Respir Res. 2020;21(1):191.

 PubMed Web of Science ®Google Scholar