Table 2. Summary of included studies on the burden of disease of respiratory syncytial virus in infants and young children.
| Author, year, (reference), country | Study design | Study period | Population | Outcome definition | Results |
|---|---|---|---|---|---|
| Medically attended RSV respiratory tract infection | |||||
| Hall et al., 2009 ((5)) US |
Prospective population-based surveillance study (NVSN) | October 2000 to September 2004, during the winter months (November–April) | Children under five years of age and had received a diagnosis of acute respiratory infection (n=5,067) | Specimens were defined as positive if RSV was detected by viral isolation or by duplicate RT-PCR assays | Of 5,067 participants, 1,014 (20%) were treated in ED and 1,161 (23%) were treated in paediatric offices: • 919 (18%) were infected with RSV • 564 (61%) were hospitalized • 355 (39%) were outpatient • 184 (52%) were treated in ED • 171 (48%) were treated in paediatric office 18% of ED visits (184/1,014) and 15% of paediatric office visits (171/1,161) were RSV-associated |
| Bourgeois et al., 2009 ((6)) US |
Prospective cohort study | 2003–2005 | Children seven years of age and younger and treated in the ED for an acute respiratory infection (n=895) | Nasopharyngeal specimens were considered RSV-positive if RSV was detected through direct immunofluorescent antibody stain and/or RT-PCR | ED visit rates: • 10.2 per 1,000 ED visits attributable to influenza • 21.5 per 1,000 ED visits attributable to RSV Children 0–23 months: 64.4 ED visits per 1,000 attributable to RSV |
| Wildenbeest et al., 2023 ((7)) Europe (Spain, Finland, England, Scotland and the Netherlands) |
Multicentre, prospective birth cohort study | 2017/07/01–2020/07/31 October 1 to May 31, parents were contacted weekly to reported ARI symptoms of their child |
Healthy term infants, defined as children born at 37 weeks or more of gestation with no evidence of significant disordersa, were included in the active surveillance cohort (n=993) | A RSV-positive ARI episode was defined as a positive test result from either in-house RT-qPCR or POCT or both | Medically attended RSV-positive ARI: • Incidence: 14.1% (12.3–16.0), n=129 infants • Incidence rate per 1,000 infant-months: 12.1 (10.2–14.3), n=131 events RSV-positive ARI: • Incidence: 26.2% (24.0–28.6), n=249 infants • Incidence rate per 1,000 infant-months: 23.7 (21.0–26.7), n=262 events |
| Li et al., 2022 ((8)) World Bank income regions (data reported for high income) |
Systematic review of studies published 2017/01/01–2020/12/31 | 2019 or before (i.e., before the onset of the COVID-19 pandemic) | Children 0–60 months of age | RSV-associated acute lower respiratory infection was defined as acute lower respiratory infection with lab-confirmed RSV infection RSV-attributable acute lower respiratory infection was defined as acute lower respiratory infection that could be causally attributable to lab-confirmed RSV-infection |
Incidence rate (UR) of RSV-associated acute lower respiratory infection in high-income regions (number of studies): • 0–3 months: 19.6 (6.5–59.7), n=3 • 3–6 months: 17.9 (4.8–66.7), n=3 • 0–6 months: 29.0 (12.9–65.0), n=4 • 6–12 months: 32.5 (19.9–53.0), n=4 • 0–12 months: 38.5 (21.6–68.8), n=5 • 0–60 months: 24.3 (13.8–42.7), n=7 |
| RSV respiratory tract infection with hospitalization | |||||
| Schanzer et al., 2006 ((9)) Canada |
Retrospective population-based study | September 1994 to August 2000 (six influenza seasons, 1994/1995–1999/2000) | Hospitalized children younger than 19 years old | Diagnostic codes (ICD-9) selected based on their association with viral respiratory illness in children. RSV-attributable bronchiolitis admissions provided a better proxy for RSV activity than RSV positive specimens alone | RSV rates were highest in infants younger than six months of age at approximately 2,000 per 100,000 |
| Papenburg et al., 2012 ((10)) Canada (QC) |
Prospective cohort study | Four consecutive winter seasons (2006/07–2009/10) | Children aged 0–35 months presenting as outpatients to paediatric clinic or hospitalized for RTI (n=1,039 episodes; 305 in the clinic and 734 in the hospital) | PCR/DNA microarray hybridization assay Hospitalization was defined as admission for more than 24 hours to a short-stay unit, paediatric ward or PICU |
RSV was the most frequently identified virus in infants and young children in hospital (n=467/734, 63.6%) with age younger than six months and prematurity associated with severe RSV cases among hospitalized children |
| Gilca et al., 2020 ((11)) Canada (QC; Nunavik) |
Retrospective cohort study | 2012/11/01–2019/06/30 Children were followed up to one year of age or until 2019/06/30 |
Nunavik infants less than one year of age hospitalized for a respiratory illness (ICD-10 codes J00-J22 at any point, n=354) | RSVH was defined as hospitalization lasting 24 hours or longer with at least one positive RSV specimen collected during hospitalization or within four days prior to admission | 113 (25%) of 458 episodes had RSV; annual average was 2.5 RSV-positive hospitalizations in high-risk infants and 16 RSV-positive hospitalizations in healthy full-term infants The overall RSVH rate per 1,000 live births in children younger than one year of age (adjusted for missed cases): • High-risk infants: 147.6 • Healthy full-term infants: 64.8 • Overall: 72.6 |
| Piesky et al., 2016 ((12)) Canada (ON) |
Retrospective chart review | 2010/01/01–2011/12/31 | Children younger than three years of age residing within the Ottawa region potentially hospitalized for RSV (true positive cohort: n=1,119, and annual incidence estimates: n=19,815) | RSV hospitalization was defined as a positive test for RSV within 72 hours of admission and if the signs and symptoms responsible for hospital admission were consistent with RSV pathophysiology | Hospital admissions in children attributable to RSV: • Younger than one year of age: 8.8% • 1–2 years of age: 4.5% • 2–3 years of age: 2.7% Incidence of RSV hospitalization per 1,000 children from 2005 to 2012: • Younger than one year of age: 10.2 • 1–3 years of age: 4.8 |
| Buchan et al., 2023 ((13)) Canada (ON) |
Population-based birth cohort study | First hospitalization in children born between 2009/05–2019/06 | Children born May 2009 to June 2015 (n=826,140) | RSV hospitalizations were identified using a validated algorithm based on ICD-10 codes and/or laboratory-confirmed outcomes | 12,573 (1.4%) incident cases of RSV hospitalization Rate of RSV-hospitalization per 1,000 patient-year (95% CI): • Range: from 29.55 (28.29–30.87) in children one month of age to 0.52 (0.47–0.57) in those 36–59 months of age • Overall: 4.23 (4.16–4.30) RSV hospitalization rates varied inversely with gestational age |
| McLaughlin et al., 2022 ((14)) US |
Systematic review and meta-analysis | Studies identified were published 2000–2020, and reported and collected 1989–2016 | Children younger than five years of age (n=25 studies gave 31 estimates) | RSV hospitalization: • 13% (n=4/31) etiologic confirmation of RSV • 10% (n=3/31) clinician-directed standard-of-care medical and laboratory records • 65% (n=20/31) administrative claims data using RSV-specific ICD-9 codes • 13% (n=4/31) combined ICD-9 claims and etiologic surveillance data |
Pooled rate of RSV-associated hospitalization per 1,000 (95% CI), n=31: • Younger than six months of age: 26.2 (24.2–28.2) • Younger than one year of age: 19.4 (17.9–20.9) • Younger than five years of age: 5.2 (4.8–5.6) |
| Stein et al., 2017 ((15)) 32 countries (26 countries reported data on RSV-associated severe ARI hospitalization) |
Systematic review and meta-analysis | Studies published 2000–2015 | Children younger than five years of age not receiving RSV immunoprophylaxis with palivizumab (n=55 studies, of those 34 reported on hospitalization for severe RSV-ARI) | Case of severe ARI included hospitalized ARI or hospitalized lower or acute lower respiratory infection, pneumonia, and bronchitis | RSV-associated ARI hospitalization per 1,000 children-year (95% CI), (number of studies): • Younger than six months: 20.01 (9.65–41.31), n=6 • Younger than 12 months: 19.19 (15.04–24.48), n=18 • Younger than five years: 4.37 (2.98–6.42), n=15 |
| Suh et al., 2022 ((16)) US |
Systematic review | Studies published 2000/01/01–2021/06/11 (data 1979–2020) | Studies of US infants younger than one year of age with clinical sequelae of RSV, and bronchiolitis (n=141 studies) | Lab-confirmed or ICD diagnostic codes for RSV hospitalization or bronchiolitis hospitalization | Five studies provided nationally representative data on annual average RSVH rates per year ranging from 11.6 (95% CI: 6.9–16.3) per 1,000 per year among infants 6–11 months of age to 50.1 (95% CI: 35.6–64.6) per 1,000 per year among infants 0–2 months of age |
| Wingert et al., 2021 ((4)) OECD countries |
Rapid review | Studies published 2014/01/01–2018/09/06 | Children 24 months of age and younger, with or without a risk factor of interest, or immunocompromised children 18 years of age and younger without palivizumab prophylaxis with lab-confirmed RSV infection (n=29 cohort studies) | Lab-confirmed RSV-hospitalization, ICU admission, oxygen support, mechanical ventilation, extracorporeal membrane oxygenation, case fatality and complications from RSV infections (e.g., secondary infection) | RR (95% CI) RSV-hospitalization (number of studies): • 29–32 wGA vs. 33–36 wGA: 1.20 (0.92–1.56), n=1 • 33–36 wGA vs. ≥37 wGA: 2.05 (1.89–2.22), n=1 • Fewer than 33 wGA vs. 39–41 wGA: 3.88 (1.13–13.30), n=1 |
| Li et al., 2022 ((8)) World Bank income regions (data reported for high income) |
Systematic review of studies published 2017/01/01–2020/12/31 | 2019 or before (i.e., before the onset of the COVID-19 pandemic) | Children 0–60 months of age | RSV-associated acute lower respiratory infection was defined as acute lower respiratory infection with lab-confirmed RSV infection RSV-attributable acute lower respiratory infection was defined as acute lower respiratory infection that could be causally attributable to lab-confirmed RSV-infection |
Hospital admission rate per 1,000 children per year due to RSV-associated acute lower respiratory infection in high income countries (number of studies): • 0–3 months (n=19): 34.7 (21.5–56.2) • 3–6 months (n=21): 20.7 (13.5–31.6) • 0–6 months (n=27): 28.4 (20.2–40.0) • 6–12 months (n=27): 11.2 (7.5–16.7) • 0–12 months (n=41): 22.0 (17.1–28.4) |
| Bont et al., 2016 ((17)) Western Countries (Canada, the US, and Europe) |
Systematic review | Studies published 1995/01/01–2015/12/31 | Children 18 years or younger | Hospitalization for RSV-related ARI or RSV-related bronchiolitis | RSV was associated with 19%–81% of all viral ARIs causing hospitalization Annual hospitalization rates per 1,000 children per year for RSV-associated ARIs: • 0–12 months: ranging from 3.2–42.7 • 1–4 years: ranging from 0.6–1.78 More than 70% of children hospitalized with RSV-associated ARIs had no underlying medical conditions Compared to influenza, RSV causes up to 16 times more hospitalizations and ED visits in children younger than five years |
| RSV respiratory tract infection with intensive care unit admissions | |||||
| Papenburg et al., 2012 ((10)) Canada (QC) |
Prospective cohort study | Four consecutive winter seasons (2006/07–2009/10) | Children aged 0–35 months presenting as outpatients to paediatric clinics or hospitalized for RTI (n=1,039 episodes; 305 in the clinic and 734 in the hospital) | PCR/DNA microarray hybridization assay Hospitalization was defined as admission for more than 24 hours to a PICU |
63.6% (n=467) were RSV-positive hospitalization 5.2% (n=24/460) of hospital admissions for RSV had ICU admission (similar for hMPV) |
| Piesky et al., 2016 ((12)) Canada (ON) |
Retrospective chart review | 2010/01/01–2011/12/31 | Children younger than three years of age residing within the Ottawa region potentially hospitalized for RSV (true positive cohort: n=1,119) | RSV hospitalization was defined as a positive test for RSV within 72 hours of admission and if the signs and symptoms responsible for hospital admission were consistent with RSV pathophysiology | Of hospitalized cohort, 5.6% (95% CI: 5.2–5.9) were admitted to PICU and 3.1% (95% CI: 2.9–3.3) were intubated |
| Buchan et al., 2019 ((18)) Canada (ON) |
Retrospective multicentre cohort study | 2009/05/01–2014/05/31 | Hospitalized children aged 0–59 months tested for respiratory viruses including RSV (n=6,364) | Monoplex or multiplex PCR, viral culture or direct immunofluorescence | ICU admission: • 5% (n=192/3,569) with no comorbidities • 10% (n=275/2,795) if one or more comorbidity |
| Buchan et al., 2023 ((13)) Canada (ON) |
Population-based birth cohort study | First hospitalization in children born 2009/05–2019/06 | Children born between May 2009 and June 2015 (n=826,140) | RSV hospitalizations were identified using a validated algorithm based on ICD-10 codes, and/or laboratory-confirmed outcomes | 8.1% required intensive care during their hospitalizations (from 22% in those fewer than 28 weeks to 7% in those 37 weeks or more gestational age) |
| Amini et al., 2019 ((19)) Canada (QC) |
Prospective surveillance study | Peak weeks of five influenza seasons (2012/2013, 2014/2015–2017/2018) | Children younger than 24 months hospitalized with respiratory symptoms (n=546) | Multiplex PCR Hospitalization for 24 hours or longer for fever/feverishness or cough or sore throat |
ICU admissions rates (p=0.07): • RSV: 3.6% • Influenza: 0% |
| Wildenbeest et al., 2023 ((7)) Europe (five sites in Spain, Finland, England, Scotland and the Netherlands) |
Multicentre, prospective birth cohort study | 2017/07/01–2020/04/01 | Healthy term infants, defined as children born 37 weeks or more of gestation with no evidence of significant disordersa, were included in the active surveillance cohort (n=993) | Parental questionnaire and hospital chart reviews, active RSV surveillance in nested cohort | Eight PICU admissions, corresponding to 5.5% of 145 RSV-associated hospitalizations and 0.09% of the total cohort Six of eight infants admitted to the ICU were younger than three months of age (median one month) |
| Suh et al., 2022 ((16)) US |
Systematic review | Studies published 2000/01/01–2021/06/11 (data 1979–2020) | Studies of US infants younger than one year of age with RSV, clinical sequelae of RSV and bronchiolitis (n=141 studies) | RSV and bronchiolitis defined as lab-confirmed and/or ICD codes | No studies reported nationally representative data. Twenty-two studies reported proportions of ICU admissions among RSV hospitalized infants (range: 6.3%–71.4%) Higher ICU admissions were observed in younger vs. older infants (up to 64.3% in those younger than six months vs. 54.5% in those six months and older; 2013–2016), preterm vs. full-term infants (52.2% vs. 33.3%; 1992–2017) From 2003 to 2007, 21.8% of infants with CHD and 13.3% of infants with CLD hospitalized for RSV had ICU admissions |
| RSV respiratory tract infection with death | |||||
| Schanzer et al., 2018 ((20)) Canada (except QC) |
Retrospective population-based study | September 2003 to August 2014 (nine influenza seasons, excluding the 2008/2009 and 2009/2010 seasons) | All patients admitted to an acute care hospital for a respiratory condition | Hospitalization with an ICD-10 code for RSV (J12.1, J20.5, J21.0, B97.4) | RSV-attributed inpatient death rate: 0.6 (95% CI: −0.1–1.3) per 100,000 population (not limited to paediatric) |
| Buchan et al., 2023 ((13)) Canada (ON) |
Population-based birth cohort study | First hospitalization in children born 2009/05–2019/06 | Children born May 2009 to June 2015 (n=826,140) | RSV hospitalizations were identified using a validated algorithm based on ICD-10 codes and/or laboratory-confirmed outcomes | 12,573 (1.4%) incident cases of RSV hospitalization A small proportion of those (0.2%) died within 30 days of discharge |
| Reichert et al., 2022 ((21)) US |
Population-based birth cohort study | 1999–2018 | All infants born to residents of the US and those who died at younger than one year of age with RSV, bronchiolitis or influenza as the cause of death (n=80,764,705 live births, 510,502 total infant deaths from all causes) | RSV was defined by at least one ICD-10 cause of death codes: B97.4 (RSV), J12.1 (RSV, influenza), J20.5 (acute bronchitis due to RSV) and J21.0 (acute bronchiolitis due to RSV) | The overall infant mortality rates from 1999 to 2018: • RSV: 6.9 (95% CI: 6.4–7.5) per 1,000,000 live births (n=561) • Bronchiolitis: 19.8 (95% CI: 18.9–20.8) per 1,000,000 live births (n=1,603) • Influenza: 6.2 (95% CI: 5.7–6.8) per 1,000,000 live births (n=504) Infant RSV mortality rates by birth year from 2008 to 2018 ranged from 8.1 (95% CI: 5.5–11.4) to 3.4 (95% CI: 1.9–5.7) per 1,000,000 live births Infant RSV mortality rates among younger than 29 wGA infants was 103.5 (95% CI: 81.8–129.1) RSV mortality burden was greatest in full-term (53.7%) infants |
| Li et al., 2022 ((8)) World Bank income regions (data reported for high income) |
Systematic review of studies published 2017/01/01–2020/12/31 | 2019 or before (i.e., before the onset of the COVID-19 pandemic) | Children 0–60 months of age | RSV-associated acute lower respiratory infection was defined as acute lower respiratory infection with lab-confirmed RSV infection RSV-attributable acute lower respiratory infection was defined as acute lower respiratory infection that could be causally attributable to lab-confirmed RSV-infection |
Case fatality rate of in-hospital deaths in high-income countries for children 0–12 months with RSV-associated acute lower respiratory infection: 0.1% (95% CI: 0.1–0.3) (n=29 studies) |
Abbreviations: ARI, acute respiratory infection; CHD, congenital heart disease; CI, confidence interval; CLD, chronic lung disease; COVID-19, coronavirus disease 2019; DNA, deoxyribonucleic acid; ED, emergency department; hMPV, human metapneumovirus; ICD, International Classification of Diseases; ICU, intensive care unit; NVSN, New Vaccine Surveillance Network; OECD, Organisation for Economic Co-operation and Development; ON, Ontario; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; POCT, point-of-care testing; QC, Québec; RR, risk ratio; RSV, respiratory syncytial virus; RSVH, respiratory syncytial virus hospitalization; RT-PCR, reverse transcriptase polymerase chain reaction; RT-qPCR, quantitative reverse transcription polymerase chain reaction; RTI, respiratory tract infection; UR, uncertainty range; US, United States; wGA, weeks gestational age
a Including cardiovascular, respiratory, renal, gastrointestinal, haematological, neurological, endocrine, immunological, musculoskeletal, oncological, or congenital disorders