Burden of disease of RSV in infants, children and pregnant women and people

Population

Infants and children (focus on 24 months of age and younger)
Pregnant women and people

Adults only

Intervention

N/A

N/A

Control

N/A

N/A

Outcome

Emergency department or other ambulatory visits due to RSV
Hospitalization due to RSV-associated disease
ICU admission due to RSV-associated disease
RSV-associated death
Preterm labour associated with RSV

Outcome not associated with RSV infection

Study design

Systematic reviews and/or meta-analyses
Any primary evidence studies (i.e., experimental, quasi and non-experimental studies)

Narrative reviews
Guidelines
Editorials, commentaries
Conference abstracts

Hall et al., 2009 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 disorders^{Table 2 footnote a}, were included in the active surveillance cohort (n=993)

An 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 ^{Footnote 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

Schanzer et al., 2006 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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

Papenburg et al., 2012 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 disorders^{Table 2 footnotea}, 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 ^{Footnote 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

Schanzer et al., 2018 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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 ^{Footnote 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)

Hause et al., 2019 ^{Footnote 22}
US

Cross-sectional study

2015/11/03–2016/05/10

Pregnant women and people in their 2^nd or 3^rd trimester enrolled prospectively during their regular prenatal visits (n=155)

Lab-confirmed acute respiratory illness

Seven of 65 (11%) pregnant women and people with ARI at their initial enrollment and eight of 77 (10%) pregnant women and people with ARI during the study period (initial or re-enrollment) had PCR-confirmed RSV infection

Four (50%) PCR-confirmed RSV ARI cases reported symptoms of a LRTI, one was hospitalized

RSV had an attack rate of 10%–13% among ambulatory pregnant women and people receiving routine prenatal care during the respiratory virus season

Hause et al., 2018 ^{Footnote 23}
US

Cross-sectional study

2015/10/01–2016/05/10

Pregnant women and people in their 2^nd or 3^rd trimester enrolled prospectively during their regular prenatal visits (n=155)

RSV infection was determined by PCR or serology

Of the 81 ARI cases, 52 (64%) respiratory pathogens were detected:

The most frequently detected viruses were rhinovirus (n=22; 27%), coronavirus (n=14; 17%) and RSV (n=8; 10%)

12 patients had fever; 17 had symptoms of LRTI

Of the seven cases with fever in the ALRTI group, three were RSV-positive (one had HRV coinfection)

Of those patients with LRTI, two reported decreased fetal heart rate and one RSV-positive case was hospitalized for respiratory illness

Regan et al., 2018 ^{Footnote 24}
Australia, Canada (ON), Israel and the US

Retrospective database study

2010–2016

Pregnant women and people aged 18–50 years who were admitted to hospital with an ARFI (n=1,604,206 pregnant women and people)

An RSV-positive ARFI hospitalization was defined as a positive RT-PCR test result within three days of hospital admission

13,694 hospitalized acute respiratory tract/febrile illness; 846 tested for RSV and influenza

2.5% (n=21) tested positive for RSV

51% (n=430) tested positive for influenza

Fewer than 1% tested positive for both influenza and RSV

Nowalk et al., 2022 ^{Footnote 25}
US

Population-based retrospective aggregate cohort study

2015/09/01–2018/08/31

Adults ages 18–64 years, 65 years and older and including pregnant women and people (n=13,174 pregnant women and people)

Aggregate data used to determine population-based RSV hospital burden

RSV burden of hospitalization ranged from 0 to 808 per 100,000 pregnant women and people:

• 2015–2016: no hospitalized cases of RSV among pregnant women and people
• 2016–2017: 431 per 100,000
• 2017–2018: 808 per 100,000

Average burden from 2015 to 2018 of 620/100,000 in pregnant women and people which was higher than the burden for non-pregnant adults 18 years and older (n=320/100,000)

Hause et al., 2021 ^{Footnote 26}
US

Retrospective case series

2010/08/01–2017/04/30

Pregnant women and people aged 14–49 years who tested positive for RSV and were hospitalized for RSV infection during pregnancy (n=10)

Variable

275,349 pregnant women and people; 1,057 tested for RSV; 25 (2%) tested positive; 10 hospitalized during pregnancy and tested positive within two weeks prior to or during hospitalization

Diagnoses: pneumonia/atelectasis (n=5), upper respiratory tract infection (n=2), asthma exacerbation (n=2), respiratory failure (n=2), sepsis (n=2)

Six had obstetrical complications (one exacerbation of pre-existing short cervix with preterm labour, three preterm contractions (two of which had co-infections), one induction for preeclampsia); one preterm birth; one ICU admission/mechanical ventilation

Hause et al., 2021 ^{Footnote 26}
US

Retrospective case series

2010/08/01–2017/04/30

Pregnant women and people whose pregnancy ended in live birth (n=10)

Hospitalization during pregnancy and positive RSV test by culture or PCR

275,349 pregnant women and people; 1,057 tested for RSV; 25 (2%) tested positive; 10 hospitalized during pregnancy and tested positive within two weeks prior to or during hospitalization

One of 10 (10%) required ICU admission and mechanical ventilation

Wheeler et al., 2015 ^{Footnote 27}
US

Case series

Winter 2014

Antepartum RSV infection treated at single tertiary care facility (n=3)

N/A

Two of three cases required ICU admission and mechanical ventilation; all three cases complicated by pre-existing lung conditions (asthma, comorbid influenza, group A streptococcus infection)

Deshmukh et al., 2014 ^{Footnote 28}
UK

Case report

Not stated

40-year-old pregnant person (n=1)

N/A

Pregnant person admitted to hospital in UK requiring ICU admission, mechanical ventilation, and emergency C-section at 33 weeks for maternal reasons (RSV pneumonitis and sepsis)

Regan et al., 2018 ^{Footnote 24}
Australia, Canada (ON), Israel and the US

Retrospective database study

2010–2016

Pregnant women and people 18–50 years of age who were admitted to hospital with an ARFI (n=1,604,206 pregnant women and people)

An RSV-positive ARFI hospitalization was defined as a positive RT-PCR test result within three days of hospital admission

13,694 hospitalized acute respiratory tract/febrile illness; 846 tested for RSV; 2.5% (n=21) tested positive by RT-PCR

No difference in preterm, small-for-gestational age and low birth weight births between RSV-positive and RSV-negative participants

Association observed between RSV positivity and subsequent preterm birth (p=0.034):

• RSV-positive participants, 29%
• RSV-negative participants, 15%

Chu et al., 2016 ^{Footnote 29}
Nepal

Prospective randomized trial

April 2011 to May 2014

Pregnant women and people in the 2^nd trimester of pregnancy and followed until six months postpartum (n=3,693; 14 RSV illness episodes over 3,554 person-year surveillance)

RSV-positive tests were determined by rt-PCR

Seven (50%) pregnant participants sought care for RSV illness; none died

Of the seven (50%) illness episodes during pregnancy, all had live births with two (29%) preterm births and a median birth weight of 3,060 grams. This compares to 469 (13%) preterm births and a median birth weight of 2,790 grams in persons without RSV during pregnancy

Hause et al., 2021 ^{Footnote 26}
US

Retrospective case series

2010/08/01–2017/04/30

Pregnant women and people whose pregnancy ended in live birth (n=10)

Hospitalization during pregnancy and positive RSV test by culture or PCR

275,349 pregnant women and people; 1,057 tested for RSV; 25 (2%) tested positive; 10 hospitalized during pregnancy and tested positive within two weeks prior to or during hospitalization

One of 10 (10%) participants had pneumonia and preeclampsia and was induced between 36 and 37 weeks