Economic burden of respiratory syncytial virus infection in adults: a systematic literature review

Figures & data

Figure 1. PRISMA diagram. Abbreviations. ICU, intensive care unit; MV, mechanical ventilation; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses. ^aConferences and years indexed in Embase were as follows: American Thoracic Society (2019–2021 abstracts); CHEST annual meeting (2019–2021 abstracts); Infectious Diseases Society of America (IDWeek) (2019–2021 abstracts); ISPOR (2019–2021 abstracts); CHEST Congress (2019–2020 abstracts). ^bTwo publications^14,84 reported on the same population.

Figure 2. Countries included in cost studies. Abbreviation. US: United States.

Figure 3. Design features of cost studies (n = 15). Abbreviations. ED, emergency department; LTCF, long-term care facilities; RSV, respiratory syncytial virus; US, United States.

Figure 4. Cost studies: Venn diagram of cost types, treatment settings, and outcome types. Abbreviations. Flu, influenza; RSV, respiratory syncytial virus; US, United States. ^aConference abstract.

Table 1. Direct US national cost burden.

Study, country(ies), setting	Study type, data dates, follow-up	Costs^a
Choi et al.^42; US; Inpatient	Multicenter, prospective cohort within a surveillance study; 15 October 2017–30 April 2018 and 15 October 2018–30 April 2019; Follow-up: not reported (appears to be the period of hospitalization)	Extrapolated national RSV hospitalization costs in adults in the US 18–49 years: $164,237,831; 95% CI, $46,330,606–$282,145,055 50–64 years: $290,202,254; 95% CI, $170,884,452–$409,520,054 ≥65 years: $810,932,993; 95% CI, $591,056,157–$1,030,809,829 Total (all ages): $1,265,409,170; 95% CI, $988,872,893–$1,541,945,445
Lonnet et al.^44 [conference abstract]; US; Inpatient	Retrospective database study; 2008–2017; Follow-up: not applicable	Total annual direct medical cost increase for RSV hospitalization events in 2008–2017 ≥60 years: $1,495–$1,796 million or $3,291–$3,955 million, depending on RSV incidence estimates

Abbreviations. CI, confidence interval; RSV, respiratory syncytial virus; US, United States.

^aConverted to 2022 US$. See Supplementary Table A3 for uninflated costs.

Table 2. Incremental costs for RSV patients versus controls.

Study, country(ies), setting	Study type, data dates, follow-up	Costs^a
Costs pre- and post-RSV diagnosis
Mesa-Frias et al.^46; US;	Retrospective longitudinal database study;	Increases in mean weekly all-cause costs in week 1 pre-RSV diagnosis versus weeks 2–8 pre-RSV: •60–64 years: $1,163
All healthcare settings	2000–2020;	≥65 years: $1,456 ≥85 years: $945 18–59 years at high risk of severe RSV: $945
	Follow-up: N/A
		Increases in mean weekly all-cause costs in week 1 post-RSV diagnosis versus weeks 2–8 pre-RSV:
		60–64 years: $10,028 ≥65 years: $12,137 ≥85 years: $18,062 18–59 years at high risk of severe RSV: $8,349
		Estimates based on Optum data except those for 18–59 years at high risk of severe RSV, which were based on MarketScan data. Cost increases calculated based on reported costs week 1 pre-RSV diagnosis, weeks 2–8 pre-RSV diagnosis, and week 1 post-RSV diagnosis
Wyffels et al.^12;	Retrospective database study;	Mean (SD) total all-cause healthcare costs for 180 days pre-diagnosis and 180 days post-diagnosis of RSV; costs include outpatient costs, inpatient costs, pharmacy costs, and other costs (durable medical equipment, home health agency, hospice, and skilled nursing facility)
US;	January 2011–December 2015;
Inpatient and outpatient	Follow-up: N/A
					Patient risk		180 days pre-RSV diagnosis	180 days post-RSV diagnosis
		Hospitalized			High risk		$38,056	$49,108
					Non–high risk		$20,476	$43,445
		Outpatient			High risk		$17,398	$19,330
					Non–high risk		$7,016	$9,503
RSV vs controls
Rafferty et al.^49; Canada; Inpatient and ED	Retrospective case-control study; 2010–2019; Follow-up: N/A	Costs for both tables include hospitalization, ED visits, and physician billing.
		Incremental costs attributed to RSV are given by mean all-cause cost per RSV case minus controls’ mean all-cause costs per RSV case
			Mean all-cause cost per RSV case				Mean incremental all-cause cost per RSV case
		Age, years	30 days		365 days		30 days	365 days
		18–49	$21,530 ± $57,084		$104,182 ± $285,945		$21,241	$99,954
		50–64	$28,220 ± $72,114		$121,036 ± $211,619		$27,753	$113,938
		65–79	$25,303 ± $51,046		$146,290 ± $313,062		$24,807	$136,416
		≥80	$20,090 ± $35,888		$112,697 ± $203,969		$19,478	$101,702
		Incremental costs are given by mean all-cause cost per RSV-attributable ARI case minus controls’ mean all-cause cost per RSV-attributable ARI case
			Mean all-cause cost per RSV-attributable ARI case				Mean incremental all-cause cost per RSV-attributable ARI case
		Age, years	30 days		365 days		30 days		365 days
		18–49	$444 ± $2,463		$2,959 ± $10,456		$290		$914
		50–64	$752 ± $4,041		$4,890 ± $17,979		$517		$1,474
		65–79	$1,491 ± $5,675		$9,600 ± $26,540		$1,104		$3,600
		≥80	$2,878 ± $7,230		$16,918 ± $34,490		$2,379		$7,646
Amand et al.^38; US;	Retrospective case-control study; 2012–2013;	Incremental differences in annual healthcare utilization and costs between the RSV patients and the matched controls over the 12-month follow-up period
All healthcare settings	Follow-up: 12 months	Setting	18–49 years	50–64 years		65–74 years	75–84 years			≥ 85 years
		Inpatient	$2,861	$3,496		$7,744	$13,660			$3,592
		ED/UC	$721	$991		$790	$864			$856
		Ambulatory visit	$1,830	$2,609		$1,916	$1,217			$4,619
		Outpatient visit	$1,433	$1,914		$5,184	$14,142			$10,078
		Rx filled	$1,352	$1,495		$2,426	$1,499			$960
		Total costs	$8,198	$10,504		$18,060	$31,381			$20,102

Abbreviations. ARI, acute respiratory infection; ED, emergency department; N/A, not applicable; RSV, respiratory syncytial virus; Rx, prescription; SD, standard deviation; UC, urgent care; US, United States.

^aConverted to 2022 US$. See Supplementary Table A4 for uninflated costs.

Table 3. Hospitalization costs.

Study, country(ies), setting	Study type, data dates, follow-up	Costs^a
Ackerson et al.^37; US; Inpatient	Observational, retrospective database study; January 2011–June 2015; Follow-up: NR	Adjusted mean cost per RSV hospitalization 60–74 years: $19,712 75–84 years: $20,884 ≥85 years: $17,222
Belk et al.^39 [conference abstract]; US; Inpatient	Retrospective, matched cohort study; 2016–2018; Follow-up: NR (appears to be admission to discharge or death)	Median hospitalization charges $27,757 (p < 0.001)
Pastula et al.^47;	Retrospective database study;	Adjusted (geometric mean) total (direct) cost of hospitalization during RSV event (total, includes immunocompromised and non-immunocompromised patients): 20–44 years: $49,442.40 45–59 years: $58,117.44 ≥60 years: $41,530.92
US;	1997–2012;
Inpatient	Follow-up: N/A
Choi et al.^42; US; Inpatient	Multicenter, prospective cohort within a surveillance study; 15 October 2017–30 April 2018 and 15 October 2018–30 April 2019; Follow-up: NR (appears to be the period of hospitalization)	Mean direct medical cost (includes ICU, nursing, pharmacy, therapy, emergency department, laboratory, radiology, and other) per RSV hospitalization 18–49 years: $12,125; 95% CI, $7,109–$18,951 50–64 years: $8,049; 95% CI, $6,260–$10,392 ≥65 years: $8,983; 95% CI, $7,583–$10,636
Chen et al.^41;	Multicenter, retrospective chart review;	Median cost of RSV hospitalization: $3,123.44
China;	1 January 2013–31 May 2019;
Inpatient	Follow-up: 30 days after discharge
Prasad et al.^48;	Retrospective surveillance study;	Median direct healthcare costs of RSV hospitalization for all adults: $3,420 per hospitalization
New Zealand;	2012–2015;
Inpatient	Follow-up: N/A
Yoon et al.^50;	Retrospective database study;	Median medical costs per admission by age group 19–49 years: $2,211.78 50–64 years: $2,391.57 ≥65 years: $3,314.48
Republic of Korea;	2012–2015;
Inpatient	Follow-up: N/A
El Sherif et al.^43;	Prospective surveillance study;	Mean direct cost of RSV hospitalizations (includes hospitalization, ICU, MV, other) per RSV case: All patients: $18,209; 95% CI, $17,568–18,852; provincial range: $16,538–$33,957 50–59 years: $16,683 60–79 years: N/R ≥80 years: $21,487
Canada;	2012–2015;
Inpatient	Follow-up: NR (appears to be during hospitalization)

Abbreviations. CI, confidence interval; ICU, intensive care unit; MV, mechanical ventilation; N/A, not applicable; NR, not reported; RSV, respiratory syncytial virus; US, United States.

^aConverted to 2022 US$. See Supplementary Table A5 for uninflated costs.

Table 4. Multiple care settings costs.

Study, country(ies), setting	Study type, data dates, follow-up	Costs^a
Rafferty et al.^49;	Retrospective case-control study;	Costs below for both tables include hospitalization, ED visits, and physician billing
Canada;	2010–2019;		Mean all-cause cost per RSV case
Inpatient and ED	Follow-up: N/A	Age, years	30 days	365 days
		18–49	$21,530 ± $57,084	$104,182 ± $285,945
		50–64	$28,220 ± $72,114	$121,036 ± $211,619
		65–79	$25,303 ± $51,046	$146,290 ± $313,062
		≥80	$20,090 ± $35,888	$112,697 ± $203,969
			Mean all-cause cost per RSV-attributable ARI case
		Age, years	30 days	365 days
		18–49	$444 ± $2,463	$2,959 ± $10,456
		50–64	$752 ± $4,041	$4,890 ± $17,979
		65–79	$1,491 ± $5,675	$9,600 ± $26,540
		≥ 80	$2,878 ± $7,230	$16,918 ± $34,490
Mao et al.^45; Europe (Belgium, United Kingdom, and the Netherlands); Outpatient	Multicenter prospective observational cohort study; 1 October–1 May in 2017–2018 and 2018–2019; Follow-up: NR	Direct cost per RSV episode: Patient: $14.28 Healthcare provider: $17.82 Healthcare payer: $6.71 Total societal costs per RSV episode: $37.54 Societal costs included cost of productivity losses

Abbreviations. ARI, acute respiratory infection; ED, emergency department; N/A, not applicable; NR, not reported; RSV, respiratory syncytial virus; US, United States.

^aConverted to 2022 US$. See Supplementary Table A6 for uninflated costs.

Table 5. Costs among high-risk patients and patients with comorbidities.

Study, country(ies), setting	Study type, data dates, follow-up	Costs^a
Mesa-Frias et al.^46;	Retrospective longitudinal database study;	Increases in mean weekly all-cause costs in week 1 pre-RSV diagnosis versus weeks 2–8 pre-RSV: 18–59 years at high risk of severe RSV: $2,765 ‒ $1,820 = $945 Increases in mean weekly all-cause costs in week 1 post-RSV diagnosis versus weeks 2–8 pre-RSV: 18–59 years at high risk of severe RSV: $10,170 ‒ $1,820 = $8,349 (MarketScan data)
US;	2000–2020;
All healthcare settings	Follow-up: N/A
Wyffels et al.^12;	Retrospective database study;	Mean (SD) total all-cause healthcare costs for 180 days pre-RSV and 180 days post-RSV diagnosis, including outpatient costs, inpatient costs, pharmacy costs, and other costs (durable medical equipment, home health agency, hospice, and skilled nursing facility)
US; Inpatient and outpatient	January 2011–December 2015; Follow-up: N/A
			Patient risk	180 days pre-RSV diagnosis		180 days post-RSV diagnosis
		Hospitalized	High	$38,056		$49,108
			Non-high	$20,476		$43,445
		Outpatient	High	$17,398		$19,330
			Non-high	$7,016		$9,503
Choi et al.^42; US; Inpatient	Multicenter, prospective cohort within a surveillance study; 15 October 2017–30 April 2018 and 15 October 2018–30 April 2019; Follow-up: NR (appears to be the period of hospitalization)	Mean all-cause direct medical cost (includes ICU, nursing, pharmacy, therapy, emergency department, laboratory, radiology, and other) per RSV hospitalization Mean observed hospital cost per case (95% CI, unadjusted)^a
		Comorbidity			Yes		No
		Cardiovascular disease			$10,581* ($8,531–$12,967)		$7,344 ($6,282–$8,701)
		Chronic lung disease			$8,362 ($7,142–$9,775)		$9,931 ($7,801–$12,516)
		Diabetes			$8,280 ($6,961–$9,884)		$9,817 ($7,873–$12,139)
		Obesity			$8,513 ($6,434–$11,587)		$9,432 ($7,943–$11,117)
		Immunosuppression			$9,111 ($7,368–11,142)		$9,178 ($7,574–$11,084)
		Neurologic			$7,438* ($5,477–$10,278)		$9,705 ($8,211–$11,452)
		Chronic kidney disease			$9,834 ($7,669–$12,393)		$8,898 ($7,411–$10,709)
		Chronic liver disease			$14,630 ($7,771–$23,403)		$8,747 ($7,535–$10,181)
		*p < 0.05 vs. no comorbidity.
		^aSimple comparisons of patients with and without the specific comorbidity, without adjustment for other comorbidities or other patient characteristics.
Pastula et al.^47;	Retrospective database study;	Adjusted (geometric mean) total (direct) cost of hospitalization during RSV event for immunocompromised patients 20–44 years: $86,186.76 45–59 years: $88,675.80 ≥60 years: $70,378.56 Adjusted (geometric mean) total (direct) cost of hospitalization during RSV event for non-immunocompromised patients 20–44 years: $32,425.32 45–59 years: $43,155.45 ≥60 years: $34,542.96
US;	1997–2012;
Inpatient	Follow-up: N/A

Abbreviations. CI, confidence interval; ICU, intensive care unit; N/A, not applicable; NR, not reported; RSV, respiratory syncytial virus; SD, standard deviation; US, United States.

^aConverted to 2022 US$. See Supplementary Table A7 for uninflated costs.

Table 6. Sequelae costs.

Study, country(ies)	Study type, data dates, follow-up	Costs^a
Sequelae
Bosco et al.^40;	Retrospective cohort study;	Mean RSV-attributable cost per cardiorespiratory hospitalization 65–74 years: $11,348 75–84 years: $9,942 ≥85 years: $9,411 All age groups: $10,136 National RSV-attributable cost of cardiorespiratory hospitalization 65–74 years: $5,679,577; 95% CI, $2,171,656–$9,187,498 75–85 years: $8,662,411; 95% CI, $3,432,688–$13,892,134 ≥85 years: $45,401,614; 95% CI, $39,519,621 -$51,283,607 ≥65 years (total for all age groups): $59,743,602; 95% CI, $45,123,966–$74,363,238 Mean influenza-attributable cost per cardiorespiratory hospitalization 65–74 years: $11,348 75–84 years: $9,942 ≥85 years: $9,411 All age groups: $10,136 National influenza-attributable cost of cardiorespiratory hospitalization 65–74 years: $5,141,048; 95% CI, $2,256,756–$8,025,341 75–84 years: $18,148,748; 95% CI, $13,871,681–$22,425,814 ≥85 years: $43,329,667; 95% CI, $38,485,958–$48,173,376 ≥65 (total for all age groups): $66,619,462; 95% CI, $54,614,395–$78,624,529
US;	6 respiratory seasons (2011–2017);
Inpatient	Follow-up: until the end of the last respiratory season

Abbreviations: CI, confidence interval; US, United States.

^aConverted to 2022 US$. See Supplementary Table A8 for uninflated costs.

Table 7. RSV costs compared with influenza costs.

Study, country(ies), setting	Study type, data dates, follow-up	Costs^a
Mao et al.^45; Europe (Belgium, United Kingdom, and the Netherlands); Outpatient	Multicenter prospective observational cohort study; 1 October–1 May in 2017–2018 and 2018–2019; Follow-up: NR	Direct cost per RSV episode: Patient: $14.28 Healthcare provider: $17.82 Healthcare payer: $6.71 Direct cost per influenza episode: Patient: $19.78 Healthcare provider: $32.09 Healthcare payer: $51.87 Total societal costs per episode: RSV: $37.54 Influenza: $91.02 Societal costs included cost of productivity losses
Chen et al.^41;	Multicenter, retrospective chart review;	Median cost of RSV hospitalization: $3,123.44
China;	1 January 2013–31 May 2019;	Median cost of influenza-related pneumonia hospitalization: $3,603.23
Inpatient	Follow-up: 30 days after discharge
Ackerson et al.^37;	Observational, retrospective database study;	Adjusted mean cost per RSV hospitalization: 60–74 years: $19,712 75–84 years: $20,884 ≥85 years: $17,222 Adjusted mean cost per influenza hospitalization: 60–74 years: $20,425 75–84 years: $18,803 ≥85 years: $15,676
US;	January 2011–June 2015;
Inpatient	Follow-up: NR
Belk et al.^39 [conference abstract];	Retrospective, matched cohort study;	Median RSV hospitalization charges: $27,757 Median influenza hospitalization charges: $22,164
US;	2016–2018;
Inpatient	Follow-up: NR (appears to be admission to discharge or death)
Pastula et al.^47;	Retrospective database study;	Adjusted (geometric mean) total (direct) cost of hospitalization during RSV event (total, includes immunocompromised and non-immunocompromised patients): 20–44 years: $49,442.40 45–59 years: $58,117.44 ≥60 years: $41,530.92 Adjusted (geometric mean) total (direct) cost of hospitalization during influenza event (total, includes immunocompromised and non-immunocompromised patients): 20–44 years: $15,152.88 45–59 years: $19,317.60 ≥60 years: $17,691.00
US;	1997–2012;
Inpatient	Follow-up: N/A

Abbreviations. CI, confidence interval; N/A, not applicable; NR, not reported; RSV, respiratory syncytial virus; US, United States.

^aConverted to 2022 US$. See Supplementary Table A9 for uninflated costs.

Figure 5. Economic gap analysis. Abbreviations: RSV, respiratory syncytial virus; US, United States. ^a Excluding transplant studies and economic models. ^b Belgium, United Kingdom, and the Netherlands. ^c Sequelae costs⁴⁰ or incremental costs of RSV when compared to a control group⁴⁹. ^d Numbers indicate total number of studies in which studied age ranges exactly match those specified here. Studies with outcomes for multiple age groups are counted more than once. ^e Bosco et al.⁴⁰ determined RSV-attributable cardiorespiratory hospitalizations (based on ICD coding) during RSV peaks.

Figure 6. Evidence limitations and gaps in the economic literature. Abbreviations: ICD, International Statistical Classification of Diseases; RSV, respiratory syncytial virus; US, United States.

Figure 7. HCRU gap analysis. Abbreviations: HCRU, healthcare resource utilization; ICU, intensive care unit; MV, mechanical ventilation; RSV, respiratory syncytial virus; US, United States. ^aAustralia, Argentina, Brazil, Canada, France, Germany, Japan, Malaysia, Mexico, Republic of Korea, South Africa, US. ^bCyprus, Italy, Portugal. ^c One US study⁶⁹ reported outcomes during an RSV surge for patients hospitalized with ARI. This study is not represented in this table. ^d Two studies had cohorts slightly different from ≥18 years: Hill-Ricciuti et al.⁷¹ included patients aged >18 years, and Falsey et al.² included high-risk adults aged ≥21 years, nine of whom were part of an 132 hospitalized cohort (age range not reported). ^e “Elderly” was not defined in Belk et al.³⁹. ^f In one US study¹¹, data were presented for age subgroups 60–74 years, ≥60 years, and ≥75 years.

Figure 8. Evidence limitations and gaps in the HCRU literature (for systematic HCRU outcomes only). Abbreviations: HCRU, healthcare resource utilization; ICU, intensive care unit; MV, mechanical ventilation; RSV, respiratory syncytial virus; US, United States. ^aBelgium, United Kingdom, and the Netherlands.

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