Abstract
Background:
Numerous studies in the U.S. have made estimates of the RSV burden among adults that vary widely due to differences in methodology, reliance on influenza surveillance, which does not adequately capture all RSV clinical symptoms, and lack of diagnostic methods to identify RSV when viral loads are low. Nevertheless, accurate burden estimates can inform healthcare planning, resource allocation and potentially, RSV vaccine policy.
Methods:
A simple method combined with statewide and local hospitalization, medical record and U.S. Census data were used to estimate population-based RSV hospitalization burden among adults ages 18–64 years, ≥65 years, and including immunocompetent, immunocompromised and pregnant individuals during 2015–2018 for Allegheny County, Pennsylvania. Economic burden of hospitalization was estimated using state-provided average hospitalization charges for comparisons across patient groups.
Results:
The largest burden was borne by adults ≥ 65 years of age whose rates per 100,000 population of that age group (939/100,000) were 7.0–9.0 times those of adults 18–64 years of age (118/100,000). Immunosuppressed patients bore the greatest relative burden of RSV hospitalizations (1,288–1,562/100,000 immunosuppressed individuals). RSV burden ranged from 0 to 808/100,000 pregnant women. Average total charges for RSV hospitalization in Allegheny County across all adults increased from $39 million in 2015–2016 to $57 million in 2016–2017 to $89 million in 2017–2018, due to both increased average charges for an acute respiratory hospitalization and increased numbers of RSV cases.
Conclusions:
These RSV burden estimates add to the body of knowledge to guide public health policy makers and offer a method for simply and easily producing population-based burden estimates.
Keywords: RSV burden, Acute respiratory illness, Retrospective cohort study, Adults
1. Introduction
The U.S. Centers for Disease Control and Prevention (CDC) estimates that respiratory syncytial virus (RSV) is responsible for 177,000 hospitalizations and 14,000 deaths among adults 65 years and older per year. [1] These estimates are based on a prospective surveillance study that was published in 2005. [2] Numerous studies in the U.S. have made estimates of RSV burden among adults. A recent review and meta-analysis of RSV burden concluded that variability in RSV estimates might be due to differences in methodology across studies, reliance on surveillance, primarily influenza surveillance, which does not adequately capture all RSV clinical symptoms, and lack of diagnostic methods to identify RSV when viral loads are low. [3] Moreover, few U.S. studies have included adults younger than 50 years. [4,5] Accurate burden estimates can assist with health care planning and resource allocation.
As the prospect of a RSV vaccine becomes more likely, accurate estimates of RSV burden across population subgroups are also needed to inform vaccination policy. Including younger as well as older adults, and high-risk groups such as the immunocompromised in RSV burden estimates will help to establish priority groups for vaccination in the event of limited supplies or high cost of vaccine.
We developed a method to produce population-based estimates of RSV burden using data from a large health system supplemented by statewide hospitalization data.[6] This method was used to conduct a retrospective aggregate cohort study to estimate the burden of RSV hospitalization in adults (≥18 years of age) overall and for population subgroups over three seasons in Allegheny County, Pennsylvania.
2. Methods
The University of Pittsburgh Institutional Review Board (IRB) determined that their approval was not required to conduct the study because all data used were deidentified. RSV hospitalization burden, i.e., prevalence of RSV hospitalization, were calculated for adult (≥18 years old) residents of Allegheny County PA who were hospitalized in Pennsylvania between September 1, 2015 and August 31, 2018. The estimates used state-level aggregated data for quarterly acute respiratory infection (ARI) hospitalizations limited to Allegheny County residents in Allegheny County Hospitals. Each hospital admission, defined generally as an encounter for which admission orders were written for a given individual, was included. These ARI hospitalizations were divided into ARI-specific and ARI-related per the ICD9/10 codes listed in Appendix 1. These aggregate data were supplemented by individual level data from the UPMC Health System (UPMC), a large integrated health system located in western and central Pennsylvania, originating and based in Allegheny County. UPMC owns approximately 60% of the hospital beds in Allegheny County. More detailed descriptions of the four data sources used in this analysis follow.
2.1. Data sources
The first data source was aggregate data from all ARI-specific and ARI-related hospitalizations in Pennsylvania for the study period that were obtained from the Pennsylvania Health Care Cost Containment Council (PHC4). These aggregated data contain variables that will allow subgroup analyses, such as age, immunosuppressed status and pregnancy. The data were provided in 3-month segments that were selected to best reflect the active RSV season of September through May. The first segment was September-November 2015, followed by successive segments from December-February, March-May, and June-August through August 2018. These data were used to determine the proportion of all Pennsylvania ARI hospitalizations that were among Allegheny County residents.
Secondly, the University of Pittsburgh Clinical Translational Science Institute (CTSI)’s Health Record Research Request (R3) system extracts data from UPMC’s electronic medical record (EMR). Admitting diagnoses and respiratory viral panel (RVP) findings from any Allegheny County adult resident who was hospitalized in one of the seven acute care UPMC hospitals located in Allegheny County were included. Admissions to specialty hospitals such as psychiatric or rehabilitation institutions were excluded. ICD codes (Appendix 1) were used to identify immunocompromised patients including solid organ transplant recipients, and pregnant population subgroups and EMR data provided demographics for the numerators.
These data were supplemented by virology test results extracted from the UPMC’s EMR by an IRB-approved honest broker, using a clinical surveillance software system (Theradoc™). Virology testing results from a nasopharyngeal swab for Allegheny County residents who received a Genmark Luminex multiplex respiratory viral panel (RVP) test while an inpatient were included. Cepheid PCR tests for RSV, often performed in the emergency department, were also included in analyses if the patient were subsequently admitted.
RVP tests may be conducted year-round but are more routinely conducted in October through April on patients presenting with acute respiratory symptoms. Because UPMC is an integrated healthcare delivery system, it uses a centralized lab for processing specimens within the county and recommendations for RVP testing are believed to be uniform across hospitals. However, as a regional transplantation center, one hospital might be likely to test more frequently. Results from repeat RVPs during a single admission were collapsed into a single variable coded as a positive finding of RSV on any RVP performed (RSV = yes/no).
Residency was established through the individual’s home zip code, using those codes listed online for Allegheny County. U.S. Census estimates for Allegheny County, PA as of July 1, 2019 [9] were used to obtain the total number of adult county residents as the denominator for overall and age group burden estimates. The U.S. Census population estimate for Allegheny County was 1,216,045 for 2019 of whom 984,996 (81%) were adults aged ≥ 18 years.
U.S. Census data provided the denominators for entire populations at risk and the percentage of pregnant women ages 20–44 in the population. Without census statistics on immunosuppression, the number of immunosuppressed individuals in the county was assumed to be the same as national estimates that approximately 3% of the adult population is immunosuppressed. [7] Estimates by race, immunosuppressed status and pregnancy (ages 20–44 years) were made by adjusting the denominators to correspond with the number of county residents in each of those categories. [8].
These data were then used to calculate RSV burden overall and by subgroups using the method previously described [6] and the equations are shown in Appendix 2. It should be noted that the sum of subgroup estimates is not equal to the overall estimate, because the overall sum of the product divided by the sum of all RVPs is not the same as the product of each ARI and RSV divided by the RVP sum. (See equations 6 and 7 in Appendix 2.).
Crude estimates of the relative economic burden of RSV hospitalizations were calculated using average charge data provided by PHC4. Average total hospitalization charges for an ARI were the sum of average charges reported to the Commonwealth for drugs, equipment, room and board, specialty sevices, ancillary services, miscellaneous, and professional services for each three-month period. Economic burden was the product of the average total charges for a RSV hospitalization during a given time period and the estimated number of RSV cases for that time period.
Data were analyzed using SAS version 9.4 (SAS Institute, Cary, NC, USA) and Excel version 18 (Microsoft Office, Redmond, WA).
3. Results
During the three respiratory virus seasons of 2015–2018, approximately 134,000–137,000 hospitalizations of adults were reported across the seven hospitals. Approximately 58% of admitted patients were females, 78% were White, 18% were Black and the remainder other races (Table 1).
Table 1.
Demographics for Allegheny County residents age ≥ 18 years hospitalized with an acute respiratory illness (ARI)*.
| Season |
|||
|---|---|---|---|
| 2015–2016 | 2016–2017 | 2017–2018 | |
| Total Allegheny County Hospitalizations** | 136,679 | 137,078 | 134,001 |
| Total ARI | 53,781 | 55,931 | 57,350 |
| ARI-related | 33,740 | 35,182 | 36,939 |
| Female sex, n (%) | 79,069 (57.9) | 79,403 (57.9) | 77,158 (57.6) |
| Race, n (%) | |||
| White | 107,845 (78.9) | 107,276 (78.3) | 104,331 (77.9) |
| African American | 24,037 (17.6) | 24,191 (17.6) | 23,773 (17.7) |
| Other | 5005 (3.7) | 5895 (4.3) | 6238 (4.7) |
Data from the Pennsylvania Health Care Cost Containment Council (PHC4).
UPMC has 60% market share in Allegheny County.
Table 2 shows the percentage of ARI that is attributable to RSV. The three-year average percent of ARI hospitalizations attributable to RSV was 4.1% for adults 18–64 years and 6.4% for those ≥ 65 years of age. (For individual values, see Appendix 3.).
Table 2.
Estimated proportion of acute respiratory illnesses (ARIs) attributable to RSV based on respiratory viral panel (RVP) tests in health system hospitals*.
| Group | 3-year average (range), % |
|---|---|
| Age ≥ 18 years | 5.7 (4.3–6.7) |
| Age ≥ 18 immunocompetent | 5.6 (4.2–6.7) |
| Age 18–64 years | 4.1 (2.7–5.3) |
| Age ≥ 65 years | 6.4 (5.1–7.3) |
| Immunosuppressed (≥18 years) | 5.9 (5.0–6.7) |
| Pregnant (20–44 years) | 5.5 (0–7.4) |
See Appendix 1 Table of ICD codes
Table 3 shows overall RSV hospitalization burden and ARI-related RSV hospitalizations. Overall RSV burden varied across the three years with the lowest rate in 2015–2016 of 236/100,000 and highest rate in 2016–2017 of 382/100,000 (Table 3). The burden of RSV followed a pattern of low burden in summer and fall and high burden in winter and spring for all three years. The largest burden was borne by adults >/= 65 years of age whose rates per 100,000 population of that age group were 7.0–9.0 times the rates of adults 18–64 years of age. Immunosuppressed patients bore the greatest relative burden of RSV hospitalizations of 1,288–1,562/100,000 immunosuppressed individuals. While there were no hospitalized cases of RSV among pregnant women in 2015–2016, burden ranged from 431 to 808/100,000 pregnant women in the other two years. Similar results were found when the hospitalized ARI-related RSV cases (those hospitalized with a high-risk condition exacerbated by an ARI) were separately analyzed (Table 3). Burden of RSV was lower among those with an ARI-related condition than overall. For example, average RSV burden/100,000 total population for ARI-related hospitalizations was 205 compared with 323 for total ARI hospitalizations. Furthermore, the ratio of ARI-related RSV burden for older adults compared with younger adults ranged from 6.5 to 8.4 over three years.
Table 3.
Population RSV hospitalization burden estimates based on total acute respiratory infection (ARI) hospitalizations and ARI-related* hospitalizations.
| Time period or group | Total ARI hospitalizations |
ARI-related hospitalizations |
||||
|---|---|---|---|---|---|---|
| Calculated RSV cases in county hospitals** (a) | RSV cases per 100,000 population (a/n)*100,000 | Calculated RSV cases in county hospitals** (b) | RSV cases per 100,000 population (b/n)*100,000 | |||
| Burden of RSV for Allegheny County adult population (≥18 years) † | ||||||
| (a) | Total adults, n = 984,996 | (b) | Total adults, n = 984,996 | |||
| 9/2015–8/2016 | 2321.6 | 236 | - | 1456.5 | 148 | - |
| Fall 2015 | 43.2 | 4 | - | 27.0 | 3 | - |
| Winter 2015 | 1019.2 | 103 | - | 618.3 | 63 | - |
| Spring 2016 | 652.4 | 66 | - | 391.6 | 40 | - |
| Summer 2016 | 57.8 | 6 | - | 39.3 | 4 | - |
| 9/2016–8/2017 | 3758.5 | 382 | - | 2364.2 | 240 | - |
| Fall 2016 | 296.2 | 30 | - | 190.6 | 19 | - |
| Winter 2016 | 1427.5 | 145 | - | 812.6 | 83 | - |
| Spring 2017 | 906.6 | 92 | - | 571.9 | 58 | - |
| Summer 2017 | 0.0 | 0 | - | 0.0 | 0 | - |
| 9/2017–8/2018 | 3465.0 | 352 | - | 2231.8 | 227 | - |
| Fall 2017 | 247.3 | 25 | - | 163.9 | 17 | - |
| Winter 2017 | 1223.2 | 124 | - | 705.8 | 72 | - |
| Spring 2018 | 1003.0 | 102 | - | 643.3 | 65 | - |
| Summer 2018 | 173.5 | 18 | - | 122.4 | 12 | - |
| 3-year average | 3181.7 | 323 | - | 2017.5 | 205 | - |
| Burden of RSV for Allegheny County immunocompetent adult population (≥18 years) † | ||||||
| (a) | Total adults n = 984,996 | Immunocompetent adults n = 955,447 | (b) | Total adults n = 984,996 | Immunocompetent adults n = 955,447 | |
| 9/2015–8/2016 | 1923.9 | 195 | 201 | 1215.3 | 123 | 127 |
| 9/2016–8/2017 | 3298.4 | 335 | 345 | 2086.0 | 212 | 218 |
| 9/2017–8/2018 | 3054.6 | 310 | 320 | 1976.3 | 201 | 207 |
| 3-year average | 2759.0 | 280 | 289 | 1759.2 | 179 | 184 |
| Burden of RSV for Allegheny County non-pregnant adult population (≥18 years) † | ||||||
| (a) | Total adults n = 984,996 | Non-pregnant adults n = 971,822 | (b) | Total adults n = 984,996 | Non-pregnant adults n = 971,822 | |
| 9/2015–8/2016 | 2285.9 | 232 | 235 | 1419.1 | 144 | 146 |
| 9/2016–8/2017 | 3664.6 | 372 | 377 | 2284.0 | 232 | 235 |
| 9/2017–8/2018 | 3393.5 | 345 | 349 | 2163.9 | 220 | 223 |
| 3-year average | 3114.6 | 316 | 320 | 1955.7 | 199 | 201 |
| Burden of RSV for Allegheny County adult population (18–64 years) † | ||||||
| (a) | Total adults n = 984,996 | Adults 18–64 years n = 753,948 | (b) | Total adults n = 984,996 | Adults 18–64 years n = 753,948 | |
| 9/2015–8/2016 | 587.7 | 60 | 78 | 381.4 | 39 | 51 |
| 9/2016–8/2017 | 1176.7 | 119 | 156 | 767.9 | 78 | 102 |
| 9/2017–8/2018 | 903.5 | 92 | 120 | 603.7 | 61 | 80 |
| 3-year average | 889.3 | 90 | 118 | 584.4 | 59 | 78 |
| Burden of RSV for Allegheny County adult population (≥65 years) † | ||||||
| (a) | Total adults n = 984,996 | Adults ≥ 65 years n = 231,049 | (b) | Total adults n = 984,996 | Adults ≥ 65 years n = 231,049 | |
| 9/2015–8/2016 | 1619.2 | 164 | 701 | 993.4 | 101 | 430 |
| 9/2016–8/2017 | 2485.6 | 252 | 1076 | 1526.8 | 155 | 661 |
| 9/2017–8/2018 | 2403.8 | 244 | 1040 | 1513.0 | 154 | 655 |
| 3-year average | 2169.5 | 220 | 939 | 1344.4 | 136 | 582 |
| Burden of RSV for Allegheny County immunosuppressed† population (≥18 years)† | ||||||
| (a) | Total adults n = 984,996 | Immunosuppressed adults n = 29,550 | (b) | Total adults n = 984,996 | Immunosuppressed adults n = 29,550 | |
| 9/2015–8/2016 | 380.7 | 39 | 1288 | 228.7 | 23 | 774 |
| 9/2016–8/2017 | 461.7 | 47 | 1562 | 279.3 | 28 | 945 |
| 9/2017–8/2018 | 411.4 | 42 | 1392 | 256.1 | 26 | 867 |
| 3-year average | 417.9 | 42 | 1414 | 254.70 | 26 | 862 |
| Burden of RSV for Allegheny County pregnant population (20–44 years) † | ||||||
| (a) | Total adults n = 984,996 | Pregnant women n = 13,174 | (b) | Total adults n = 984,996 | Pregnant women n = 13,174 | |
| 9/2015–8/2016 | 0.0 | 0 | 0 | 0.0 | 0 | 0 |
| 9/2016–8/2017 | 106.5 | 11 | 808 | 96.4 | 10 | 732 |
| 9/2017–8/2018 | 56.8 | 6 | 431 | 51.6 | 5 | 392 |
| 3-year average | 81.7 | 8 | 620 | 74.0 | 8 | 562 |
ARI-related hospitalization = those hospitalized with a high-risk condition exacerbated by an ARI.
See Appendix 2 for equations 1–5
See Appendix 2 for equations 6 & 7
Includes solid organ transplants, n estimated at 3% of the adult population.
Crude estimates of the relative economic burden of RSV are shown in Table 4. Average charges for ARI increased from $249,135 in 2015–2016 to $286,053 in 2017–2018, as would be expected. Among older, younger and immunosuppressed adult groups, average charges were generally similar. Only pregnant women had lower average charges that were about 36% of the average charge for adults overall. Over three years, the total average charges of RSV hospitalizations were approximately $182 million. The majority of these charges ($122 million) were attributable to older adults who comprised 70% of those hospitalized with RSV, with charges for younger adults less than half that amount ($59 million).
Table 4.
Estimated economic burden of RSV hospitalizations for Allegheny County residents based on average total charges*.
| Season | RSV hospitalizations |
||
|---|---|---|---|
| Average Charges ($) (a) | Number (b) | Total Charges ($) (a*b) | |
| All adults, age ≥ 18 years | |||
| 9/2015–8/2016 | 249,134.97 | 146 | 36,373,706 |
| 9/2016–8/2017 | 271,437.45 | 211 | 57,273,302 |
| 9/2017–8/2018 | 286,053.23 | 311 | 88,962,555 |
| Total RSV charges for 3 years | 182,609,563 | ||
| Immunocompetent, age ≥ 18 years | |||
| 9/2015–8/2016 | 248,660.48 | 108 | 26,855,332 |
| 9/2016–8/2017 | 270,922.64 | 160 | 43,347,623 |
| 9/2017–8/2018 | 285,247.06 | 256 | 73,023,247 |
| Total RSV charges for 3 years | 143,226,202 | ||
| Not pregnant, age ≥ 18 years | |||
| 9/2015–8/2016 | 252,765.80 | 146 | 36,903,807 |
| 9/2016–8/2017 | 275,012.87 | 207 | 56,927,665 |
| 9/2017–8/2018 | 290,459.86 | 308 | 89,461,636 |
| Total RSV charges for 3 years | 183,293,108 | ||
| All adults, ages 18–64 years | |||
| 9/2015–8/2016 | 269,166.42 | 50 | 13,458,321 |
| 9/2016–8/2017 | 295,464.69 | 69 | 20,387,063 |
| 9/2017–8/2018 | 310,244.10 | 82 | 25,440,016 |
| Total RSV charges for 3 years | 59,285,400 | ||
| All adults, age ≥ 65 years | |||
| 9/2015–8/2016 | 237,236.08 | 96 | 22,774,663 |
| 9/2016–8/2017 | 257,243.54 | 142 | 36,528,582 |
| 9/2017–8/2018 | 272,695.55 | 229 | 62,447,281 |
| Total RSV charges for 3 years | 121,750,526 | ||
| Immunosuppressed ** | |||
| 9/2015–8/2016 | 252,057.95 | 38 | 9,578,202 |
| 9/2016–8/2017 | 275,073.38 | 51 | 14,028,742 |
| 9/2017–8/2018 | 291,999.50 | 55 | 16,059,972 |
| Total RSV charges for 3 years | 39,666,916 | ||
| Pregnant † | |||
| 9/2015–8/2016 | 0 | 0 | 0 |
| 9/2016–8/2017 | 100,360.53 | 4 | 401,442 |
| 9/2017–8/2018 | 105,181.20 | 3 | 315,544 |
| Total RSV charges for 3 years | 716,986 | ||
Data from the Pennsylvania Health Care Cost Containment Council.
Includes solid organ transplants, n estimated at 3% of the adult population.
Pregnant women ages 20–44 years.
4. Discussion
Among all adults in this population-based study, we found that 5.7% of ARI hospitalizations were attributable to RSV with a slightly higher rate (6.4%) among older patients. By comparison, other studies have reported rates ranging from 2.9% to 7.6% for adults ≥ 18 years and 5.7%-12% for adults ≥ 65 years. [4,9–11] Our values align with previous studies, despite the differences in methodologies across studies. Conversely, the percent of ARI hospitalizations among immunosuppressed patients attributable to RSV in our study (5.9%) was lower than rates reported among lung transplant patients (11.6%-16%), [10] but higher than rates reported among adults with cardiorespiratory disease (1.6%-2.3%). [12].
Since the identification of RSV as a significant cause of morbidity and mortality among older adults, an increasing number of studies have attempted to describe its epidemiology and quantify its public health burden in adults of all ages. These studies have used a variety of techniques including population-based data sources such as national health surveys [13] and insurance data-bases;[4] surveillance;[14–17] and modeling; [12] and have been conducted worldwide. [3,9,18] In general, they have found that: 1) RSV is more difficult to detect in adults without using the highly sensitive polymerase chain reaction (PCR) assays because the viral load is less in adults and RSV’s duration is shorter than in children; [9] 2) incidence of RSV increases with increasing age in adults, [5,10] especially among those over age 65 years – the opposite of what is found in children; [4] 3) incidence of RSV has increased over time, especially in those over age 60 years; [13,19] 4) most hospitalizations and deaths occur in infants and adults over age 65 years; [10] 5) an estimated 7% of documented RSV cases require hospitalization; [4] and 6) among adults, higher risk of severe disease is more common among the severely immunocompromised, frail elderly and those with chronic cardiac and pulmonary dis-ease.[3,5] Furthermore, in comparison with influenza, with which RSV shares an active season, variability of severity across seasons is less with RSV, [20] but the clinical burden of RSV is greater than influenza, with the average duration of illness being 3 days longer for RSV, [13,20] and RSV resulting in higher mortality. [13].
The value of this study is that it used a simple approach to estimate RSV burden that combined population-based data with clinical testing data to calculate county-wide adult RSV estimates in a metropolitan area and in a health system with 60% market share of hospital beds. Over three seasons, we estimated that there were 322 hospitalized adult RSV cases/100,000 total adult population, rising to 950 adults ≥ 65 years hospitalized with RSV/100,000 population of adults ≥ 65 years. Previous surveillance studies have reported 49–50/100,000 in New York City in 2017–2019 for all adults; [16] 23.6/100,000 for all adults and 99.2/100,000 adults ≥ 65 years in New Zealand in 2012–2015; [11] 100/100,000 adults ≥ 50 years and 20/100,000 adults 18–49 years in 2009–2010 in middle Tennessee; [14] 150.1/100,000 for adults ≥ 50 years in 2006–2009 in middle Tennessee. [15] Two reviews and meta-analyses estimated RSV hospitalization burden in industrialized nations to be 100/100,000 for adults ≥ 65 years [18] and in the US for adults ≥ 50 years to be 190–254/100,000. Population-based studies reported RSV hospitalizations among adults ≥ 65 years from Israel to be 9/100,000 [19] and from the UK to be 156/100,000. [12].
We also estimated RSV hospitalization burden among those with ARI-related hospitalizations such as congestive heart failure, asthma exacerbation, or COPD with a three-year average burden ranging from 85 to 588/100,00 in their respective age groups. Most previous studies did not separately analyze high-risk adults, or used different methods to define high-risk populations. Prasad et al reported burden per 100,000 population in New Zealand of 49.8 for those with asthma, 55.0 for those with coronary artery disease, 69.9 for those with COPD and 79.3 for those with congestive heart failure. [17] These rates represent 7–36 times the burden of low risk patients. In the US, rates for those with cardiorespiratory diagnoses ranged from 49 to 78/100,000 in 1997–2009. [21] Whereas, in the UK, Fleming reported burden for those with COPD to be 10/100,000 and those with cardiorespiratory diagnosis to be 69/100/000 population for the years 1995–2009. [12] One recent study from the US reported rates of approximately 500–1400 per 100,000 among adults ≥ 65 years with COPD, coronary artery disease and congestive heart failure. Across all ages, rates of RSV were 3.7–7.0 times higher for those with COPD and 3.2–13.4 times higher for those with coronary artery disease. [5].
Unlike many RSV hospitalization burden studies, we estimated burden among two special populations – the immunosuppressed and pregnant women. Burden among immunosuppressed patients was low (42/100,000) compared with all adults and older adults in the county, but was ten times higher than rates reported from 1997 to 2012 (0.5–4.6/100,000). [13] Among the estimated 3% of adult county residents who were immunosuppressed, burden was especially high (1410/100,000). This value may be inflated because Allegheny County is home to two academic medical centers, both of which have transplant and cancer centers. Patients travel from outlying counties to receive advanced treatment and likely are hospitalized in Allegheny County hospitals when they are ill with a respiratory virus such as RSV because of their medical complexity.
Similarly, maternity care is limited to a few hospitals in the county and the region. However, three-year average RSV hospitalization burden for pregnant women was quite low (7 cases/100,000 adult population) with no cases reported in the 2015–2016 season. Using pregnant women only as the denominator, this rate increased over 100-fold. These burden values, though small, suggest that RSV infection can be severe enough in pregnant women to warrant hospitalization. Only one other recent study was identified that reported on RSV burden among pregnant women. This multi-center surveillance study found an extremely low incidence of RSV (0.1%, n = 21) among 13,694 pregnant women admitted for acute respiratory or febrile illness. RSV cases were significantly (P = 0.046) more likely to have a pneumonia diagnosis than non-RSV cases [22].
The economics of RSV has been measured in a number of ways, including health care utilization (outpatient, Emergency Department, hospitalization), [4] hospital length of stay (LOS), admission to an intensive care unit, use of supplemental oxygen or mechanical ventilation (MV), discharge to a care facility. [13,23,24] We did not have this type of data available to us, but we were able to estimate average charges associated with RSV hospitalization that ranged from $91,000–105,000 for pregnant women to $252,000–292,000 for immunosuppressed adults, with average costs near $250,000 for most non-pregnant adults. The hospitalization charges differences between young, pregnant women and other age groups suggest less severe disease and shorter length of stay.
Prevention of RSV hospitalization depends on preventing severe disease in vulnerable populations, i.e., preventing RSV-associated lower respiratory infection -- a stated goal for RSV vaccination. [25] As of 2021, there were eight RSV vaccines in development for use in older adults, including one mRNA vaccine. [26] Understanding the populations for whom RSV poses the greatest risk of severe disease, hospitalization, and the highest associated costs will help to shape future RSV vaccine policy decisions.
4.1. Strengths and limitations
This study used large data sets from state and local hospital systems across a range of age groups and with various high-risk conditions. The RVPs used PCR testing – the most accurate means of detecting and discriminating among viruses and RVPs were the workhorse of viral testing at our institutions during the study period, instead of more limited testing such as a single-plex influenza test. However, we cannot completely account for the fact of variable (i.e., not systematic) testing patterns due to the seasonality of respiratory virus epidemiology, clinician patterns of test ordering, or clinician perceived risk of severe outcomes to certain patients, such as the immunocompromised, who may be more likely to be tested. The high market share of the UMPC Health System [27] in the county is a strength because it demonstrates the representativeness of the UPMC data which come from both community and tertiary care hospitals. Unlike other estimates, we were able to separate RSV burden by hospitalizations due to ARI only and those due to exacerbations of chronic disease due to ARI. However, there is the possibility that cases were missed because the data sets only reflected insured individuals who would be in health insurance databases. For privacy concerns, the state would only provide aggregated data which precluded our ability to analyze subgroups such as those with immunocompromising conditions by age groups or more granular age groupings. Finally, the economic burden estimates are crude because they rely on average charges, a variable reflection of actual costs, [28] but they provide an opportunity for comparison among risk groups.
5. Conclusions
A review of RSV incidence estimated worldwide [3] concluded that it is essential to generate high-quality estimates of RSV disease burden to accurately assess the potential public health value of interventions to prevent and treat adult RSV. Our simple method permits calculation of population-based estimates using multiple data sources. The age- and risk group specific data presented will help to guide priorities for RSV vaccine policy. The economic burden estimates may be used to compare costs among risk groups.
Supplementary Material
6. Funding
This work was supported by a research grant from Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. and by the National Institutes of Health (NIH) Grant Number UL1-TR-001857. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. or the NIH. Dr Zimmerman was supported by the University for this project.
The Pennsylvania Health Care Cost Containment Council (PHC4) is an independent state agency responsible for addressing the problem of escalating health costs, ensuring the quality of health care, and increasing access to health care for all citizens regardless of ability to pay. PHC4 has provided data to this entity in an effort to further PHC4’s mission of educating the public and containing health care costs in Pennsylvania.
PHC4, its agents, and staff, have made no representation, guarantee, or warranty, express or implied, that the data–financial, patient, payor, and physician specific information–provided to this entity, are error-free, or that the use of the data will avoid differences of opinion or interpretation. This analysis was not prepared by PHC4. This analysis was done by the University of Pittsburgh. PHC4, its agents and staff, bear no responsibility or liability for the results of the analysis, which are solely the opinion of this entity.
Footnotes
Declaration of Competing Interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MPN reports an investigator-initiated grant from Merck & Co. outside the submitted work. RKZ and MPN report an investigator-initiated grant from Sanofi Pasteur outside the submitted work.
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://doi.org/10.1016/j.vaccine.2022.05.077.
References
- [1].Centers for Disease Control and Prevention. Respiratory Syncytial Virus Infection (RSV). Updated 12/18/2020. Accessed 12/10/2021, https://www.cdc.gov/rsv/research/us-surveillance.html [Google Scholar]
- [2].Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005;352 (17):1749–59. [DOI] [PubMed] [Google Scholar]
- [3].Htar MTT, Yerramalla M, Moïsi J, Swerdlow D. The burden of respiratory syncytial virus in adults: a systematic review and meta-analysis. Epidemiol Infect 2020;148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Tong S, Amand C, Kieffer A, Kyaw MH. Incidence of respiratory syncytial virus related health care utilization in the United States. Journal of Global Health. 2020;10(2). [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Jin X, Ren J, Li R, Gao Ya, Zhang H, Li J, et al. Global burden of upper respiratory infections in 204 countries and territories, from 1990 to 2019. EClinicalMed 2021;37:100986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [6].Balasubramani G, Nowalk MP, Eng H, Zimmerman RK. Estimating the burden of adult hospitalized RSV infection using local and state data-methodology. Human Vacc Immunotherapeu 2022;18(1):1958610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [7].Harpaz R, Dahl RM, Dooling KL. Prevalence of immunosuppression among US adults, 2013. JAMA 2016;316(23):2547–8. [DOI] [PubMed] [Google Scholar]
- [8].Bureau USC. American Community Survey 1-year estimates. Updated 2020. Accessed 12/10/2021, https://censusreporter.org/profiles/05000US42003-allegheny-county-pa/
- [9].Ali A, Lopardo G, Scarpellini B, Stein RT, Ribeiro D. Systematic review on respiratory syncytial virus epidemiology in adults and the elderly in Latin America. Int J Infect Dis 2020;90:170–80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Colosia AD, Yang J, Hillson E, Mauskopf J, Copley-Merriman C, Shinde V, et al. The epidemiology of medically attended respiratory syncytial virus in older adults in the United States: a systematic review. PLoS ONE 2017;12(8): e0182321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Prasad N, Newbern EC, Trenholme AA, Thompson MG, McArthur C, Wong CA, et al. The health and economic burden of respiratory syncytial virus associated hospitalizations in adults. PLoS ONE 2020;15(6):e0234235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Fleming DM, Taylor RJ, Lustig RL, Schuck-Paim C, Haguinet F, Webb DJ, et al. Modelling estimates of the burden of Respiratory Syncytial virus infection in adults and the elderly in the United Kingdom. BMC infect dis 2015;15(1):443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [13].Pastula ST, Hackett J, Coalson J, et al. Hospitalizations for Respiratory Syncytial Virus Among Adults in the United States, 1997–2012. Oxford University Press; US; 2017:ofw270. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Widmer K, Griffin MR, Zhu Y, Williams JV, Talbot HK. Respiratory syncytial virus- and human metapneumovirus-associated emergency department and hospital burden in adults. Influenza Other Respi Viruses 2014;8(3):347–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Widmer K, Zhu Y, Williams JV, Griffin MR, Edwards KM, Talbot HK. Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults. research support, N.I.H., extramural. J Infect Dis 2012;206(1):56–62. 10.1093/infdis/jis309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Sieling WD, Goldman CR, Oberhardt M, Phillips M, Finelli L, Saiman L. Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York City. Influenza Other Respir Viruses Jan 26 2021;15(5):670–7. 10.1111/irv.12842. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17].Prasad N, Walker TA, Waite B, et al. Respiratory syncytial virus–associated hospitalizations among adults with chronic medical conditions. Clinical Infectious Diseases. 2021;73(1):e158–e163. [DOI] [PubMed] [Google Scholar]
- [18].Shi T, Denouel A, Tietjen AK, et al. Global disease burden estimates of respiratory syncytial virus–associated acute respiratory infection in older adults in 2015: a systematic review and meta-analysis. The Journal of infectious diseases. 2020;222(Supplement_7):S577–S583 [DOI] [PubMed] [Google Scholar]
- [19].Glatman-Freedman A, Kaufman Z, Applbaum Y, Dichtiar R, Steiman A, Gordon E-S, et al. Respiratory syncytial virus hospitalization burden: a nation-wide population-based analysis, 2000–2017. J Infect 2020;81(2):297–303. 10.1016/j.jinf.2020.05.078. [DOI] [PubMed] [Google Scholar]
- [20].Fleming DM, Elliot AJ, Cross KW. Morbidity profiles of patients consulting during influenza and respiratory syncytial virus active periods. Epidemiol Infect 2007;135(7):1099–108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [21].Matias G, Taylor R, Haguinet F, Schuck-Paim C, Lustig R, Shinde V. Estimates of hospitalization attributable to influenza and RSV in the US during 1997–2009, by age and risk status. BMC Public Health 2017;17(1):271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [22].Regan AK, Klein NP, Langley G, et al. Respiratory syncytial virus hospitalization during pregnancy in 4 high-income countries, 2010–2016. Clinical Infectious Diseases. 2018;67(12):1915–1918. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [23].Schmidt H, Das A, Nam H, Yang A, Ison MG. Epidemiology and outcomes of hospitalized adults with respiratory syncytial virus: a 6-year retrospective study. Influenza Other Respir Viruses 2019;13(4):331–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Volling C, Hassan K, Mazzulli T, Green K, Al-Den A, Hunter P, et al. Respiratory syncytial virus infection-associated hospitalization in adults: a retrospective cohort study. BMC Infect Dis 2014;14(1):1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Dudas RA, Karron RA. Respiratory syncytial virus vaccines. Clin Microbiol Rev 1998;11(3):430–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [26].Stephens LM, Varga SM. Considerations for a respiratory syncytial virus vaccine targeting an elderly population. Vaccines 2021;9(6):624. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [27].System UH. UPMC Unaudited Financial and operating report for the period ended September 30, 2021. Accessed 1/22, 2022. https://cdn.upmc.com/-/media/upmc/about/finances/documents/cy2021-q3-financial-and-operating-report.pdf?la=en&rev=cb7a0fe0643c4db5b90e47aab5d02ad0&hash=296E01D8E153D221CDF4A017418A17D2. [Google Scholar]
- [28].Arora V, Moriates C, Shah N. The challenge of understanding health care costs and charges. AMA J Ethics 2015;17(11):1046–52. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.