Key Points
Question
What is the incidence of hospitalizations for community-acquired pneumonia (CAP), pneumococcal CAP, and pneumococcal CAP that can be potentially prevented with the recently approved adult-specific 21-valent pneumococcal conjugate vaccine (V116)?
Findings
In this cross-sectional study including adults residing in defined catchment areas in Tennessee and Georgia, the overall annual incidence of hospitalizations for all-cause CAP was 340 per 100 000 adults. The incidence of hospitalizations for pneumococcal CAP was 43 per 100 000 adults, and for pneumococcal CAP due to serotypes included in V116 was 30 per 100 000 adults.
Meaning
There is a large burden of hospitalizations for CAP among US adults; these results suggest a sizable fraction of CAP was caused by Streptococcus pneumoniae, especially by serotypes covered by V116.
This cross-sectional study examines annual incidence of community-acquired pneumonia, including pneumococcal community-acquired pneumonia preventable with recently approved vaccines, in 2 Southern US states.
Abstract
IMPORTANCE
Although the use of pneumococcal conjugate vaccines (PCV) has reduced the overall burden of pneumococcal disease, recent measurements of pneumococcal pneumonia incidence are lacking.
OBJECTIVE
To prospectively quantify the burden of pneumococcal pneumonia and to assess the potential impact of the recently approved adult-specific 21-valent pneumococcal conjugate vaccine (V116).
DESIGN, SETTINGS, AND PARTICIPANTS
This cross-sectional study for prospective active surveillance included adults residing in defined catchment areas in Tennessee and Georgia hospitalized with clinical and radiographical evidence of community-acquired pneumonia (CAP) at 3 hospitals between 2018 and 2022. Data were analyzed from July 2024 to January 2025.
MAIN OUTCOMES AND MEASURES
Pneumococcal etiology was determined using an on-market serotype-agnostic urinary antigen test, serotype-specific urinary antigen detection assays covering 30 serotypes, and routine clinical tests. Overall and age-stratified incidence rates for pneumonia hospitalizations were estimated accounting for the probability of enrollment and hospital market share of enrolling hospitals within the catchment area.
RESULTS
Among 2016 patients hospitalized for CAP, the median (IQR) age was 60.1 (47.0-70.2) years; 726 patients (36.0%) were Black, 81 (4.0%) were Hispanic, and 1209 (60.0%) were White; 1863 patients (92.4%) lived in a community dwelling. A total of 279 patients (13.8%) hospitalized for CAP had evidence of pneumococcal pneumonia, and 198 (9.8%) had detection of serotypes included in V116. The overall estimated annual incidence of hospitalizations for all-cause CAP was 340 per 100 000 adults. The incidence of hospitalizations for pneumococcal CAP and pneumococcal CAP due to serotypes included in V116 was 43 and 30 per 100 000 adults, respectively. The burden of all-cause and pneumococcal CAP was consistently highest among adults age 65 years or older.
CONCLUSIONS AND RELEVANCE
This prospective surveillance study demonstrated a large burden of hospitalizations for CAP among US adults, with the highest burden of disease among adults age 65 years or older. A sizable fraction of CAP was caused by Streptococcus pneumoniae, especially by serotypes included in V116.
Introduction
Pneumonia remains a leading cause of morbidity and mortality globally, with Streptococcus pneumoniae persisting as a leading bacterial cause of community-acquired pneumonia (CAP).1,2,3,4,5 Pneumococcal infections accounted for approximately 10% to 12% of adult hospitalizations for CAP in the US during the era of widespread use of 13-valent pneumococcal conjugate vaccine (PCV13).6,7,8 Although the use of PCV13 and the earlier 7-valent formulation (PCV7) helped reduce the burden of pneumococcal pneumonia, their benefits are limited to serotypes included in the vaccine formulation, and additional efforts are needed to further reduce the burden of pneumococcal infections. Furthermore, while the introduction of PCVs has led to substantial reductions in pneumococcal diseases caused by serotypes covered by the vaccines, the emergence of other pneumococcal serotypes not covered by the vaccines has been reported, in particular after widespread use of the first generation PCV that targeted 7 serotypes.8 This replacement phenomenon has fostered the development of new vaccines with expanded coverage.8
As new PCV programs are designed, approved, and implemented to incorporate expanded formulations, such as the recently approved adult-specific 21-valent pneumococcal conjugate vaccine (V116),9,10,11,12 it is important to monitor the burden of pneumococcal pneumonia and the distribution of pneumococcal serotypes causing pneumonia. Examining the potential preventable burden of disease conferred by pneumococcal vaccination programs is of great public health interest, but it is difficult to ascertain using traditional diagnostic techniques. While bacterial cultures of blood and other normally sterile body fluids are highly specific for the detection of invasive pneumococcal disease and identification of pneumococcal serotypes, cultures are not highly sensitive, and the majority of pneumococcal pneumonias are thought to be noninvasive. Thus, it is challenging to identify pneumococcal infections and the involved serotypes accurately by relying on passive clinical surveillance with bacterial cultures. Novel serotype-specific urinary antigen detection (SSUAD) assays are more sensitive in detecting pneumococcal infections and have allowed the identification of many pneumococcal serotypes in patients with noninvasive pneumonia.6,7,8,13,14 We conducted a multicenter prospective active surveillance study using SSUAD assays to quantify the incidence of adult hospitalizations for: (1) all-cause CAP, (2) pneumococcal CAP, and (3) pneumococcal CAP caused by serotypes included in V116, which was not commercially available during the study period.
Methods
This cross-sectional study is part of the ongoing Pneumococcal Pneumonia Epidemiology, Urine serotyping and Mental Outcomes (PNEUMO) program, a multicenter, prospective, active surveillance study designed to examine the epidemiology of hospitalizations for CAP among adults. PNEUMO is coordinated by Vanderbilt University Medical Center and encompasses the following enrolling hospitals: Vanderbilt University Medical Center (Nashville, Tennessee), Emory University Hospital (Atlanta, Georgia), and Emory Midtown Hospital (Atlanta, Georgia). The study protocol was reviewed and approved by the institutional review boards of Vanderbilt University Medical Center and Emory University.6 This study report followed the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Selection Criteria and Enrollment
The selection criteria and enrollment in the PNEUMO study have been previously described.6 In brief, at each participating hospital, adults hospitalized (inpatient or observation status) with clinical and radiographic evidence of CAP were prospectively identified and approached for enrollment. Trained study personnel enrolled adult patients aged 18 years old who provided informed consent to participate and who met eligibility criteria: hospitalized or in observation status with a clinical syndrome consistent with acute lower respiratory tract infection, radiographical evidence compatible with pneumonia, and ability to provide a urine sample. Patients who developed pneumonia 48 hours or later from hospital admission were excluded (enrollment and selection criteria details available in eMethods in Supplement 1).
Patients enrolled between September 1, 2018, and October 31, 2022, were included in this analysis. During the emergence of COVID-19, a temporary enrollment pause occurred at each site due to pandemic social distancing restrictions. The enrollment pause at Vanderbilt occurred between September 1, 2020, and October 31, 2020, and at the 2 Emory hospitals between March 11, 2020, and January 5, 2021. To enable the calculation of population-based incidence, this analysis was restricted to patients enrolled in the PNEUMO study who resided in defined catchment areas for each of the enrolling sites. For Vanderbilt, the catchment area was comprised of 9 Tennessee counties, including Davidson County, where Vanderbilt Hospital is located. For the Emory Hospitals, the catchment area was comprised of 8 Georgia counties, including DeKalb County, where the Emory surveillance hospitals are located (eMethods in Supplement 1).
Data and Specimen Collection
Detailed information on sociodemographic characteristics (including race and ethnicity [categorized by American Indian or Native Alaskan, Asian, Black, Native Hawaiian or Pacific Islander, White, or other]) and clinical data were collected by trained study personnel through interview of the patients or proxies and systematic review of medical records. Data on in-hospital clinical outcomes included organ support therapies, hospital length of stay, intensive care unit admission, and in-hospital mortality.6 Results of clinical laboratory tests completed as part of routine care, including blood cultures and respiratory or normally sterile compartment specimen cultures, were captured. Enrolled patients had a urine sample collected within 72 hours of hospital admission to determine pneumococcal etiology using the assays described below.
Pneumococcal Urinary Antigen Detection Testing
Each urine sample was aliquoted and tested in 2 ways. First, the local study team completed a Streptococcus pneumoniae antigen card test (Abbott). This is an on-market serotype-agnostic test for detection of pneumococcal cell wall C-polysaccharide, which is common to all pneumococcal serotypes but does not distinguish among specific serotypes. Second, a separate urine aliquot was frozen and shipped to a central laboratory for testing with proprietary SSUAD assays that simultaneously assess for 30 distinct pneumococcal serotypes, including all serotypes in PCV15, PCV20, and V116 (except for 15B) (eTable 1 in Supplement 1). In a previous study that examined the performance of these assays, using samples from patients with known pneumococcal disease status as reference, the estimated clinical sensitivity of the SSUAD assays was 86.4% and specificity was 96.5% across 30 pneumococcal serotypes.6,15,16
Classification of Pneumococcal Etiology
Classification of pneumococcal etiology was based on results of the S pneumoniae antigen card assay, SSUAD assays, and laboratory testing completed as part of routine care. The routine care results included blood cultures collected within 48 hours of hospital admission, respiratory specimen cultures (eg, sputum, tracheal aspirate) collected within 48 hours of hospital admission that fulfilled prespecified quality criteria (25 white blood cells per low power field or more and 10 epithelial cells per low power field or less), and cultures of normally sterile compartments (eg, cerebrospinal, synovial and pleural). Pneumococcal serotype classification and distribution according to existing pneumococcal conjugate vaccines (PCV15, PCV20, and V116) was based on SSUAD results.
Statistical Analysis
We estimated incidence for 3 types of adult pneumonia hospitalizations: (1) all-cause CAP; (2) pneumococcal CAP (regardless of serotype); and, (3) pneumococcal CAP caused by serotypes included in V116. Patients in these groups were characterized using descriptive statistics encompassing sociodemographic features, clinical history, and in-hospital outcomes experienced during the course of their hospitalizations. The distribution of detected pneumococcal serotypes was characterized according to their coverage by current pneumococcal conjugate vaccines.
Methodological details for incidence rate calculations are included in the eMethods section in Supplement 1. In brief, we first calculated the number of total hospitalizations for each pneumonia group accounting for the probability of enrollment at each study site (ie, the probability of enrolling in the study given fulfilment of eligibility criteria). We also accounted for the estimated probability of hospitalization for acute respiratory illness in a surveillance hospital among all hospitalizations for acute respiratory illness among residents of the catchment area (ie, the market share of surveillance hospitals for acute respiratory illness-related hospitalizations among catchment area residents) (eTable 2 in Supplement 1). Hospital market share estimates were derived from examination of data from a registry of all hospitalizations in Tennessee (Vanderbilt site) or an estimation based on reportable diseases under surveillance in the catchment area in Georgia (Emory sites).
The number of hospitalizations represented the numerators for rate calculation and were derived from all enrolling sites during periods of concurrent enrollment or from a single site when pandemic restrictions prevented continuous enrollment. Incidence rates were calculated for 4 consecutive years. The first year, from September 2018 through August 2019, included all enrollment sites. The second year, from September 2019 through August 2020, only included Vanderbilt data as Emory hospitals could not enroll during several months due to pandemic restrictions. The third year, from November 2020 through October 2021, included all enrollment sites. Similarly, the fourth year, from November 2021 through October 2022, also included all enrollment sites.
We derived rate denominators from corresponding midyear census estimates for the catchment areas.17 All rates and their corresponding 95% CIs were computed per year and expressed per 100 000 population (eMethods in Supplement 1). Incidence rate estimates were calculated overall and for three age groups: ages 18 to 49 years, 50 to 64 years, and 65 years or older. As the beginning of the COVID-19 pandemic brought unique challenges to study teams for enrolling all adult patients hospitalized with CAP, secondary analyses to estimate incidence rates were conducted without including the second study year. Statistical analyses were performed in R version 4.4.0 (R Project for Statistical Computing).
Results
Study Population
During the study period, 5385 adult patients hospitalized with a presentation potentially consistent with pneumonia were screened for eligibility, and 3278 patients were enrolled at the surveillance hospitals. After exclusion of patients without radiographic evidence compatible with pneumonia (235 patients), those who withdrew from the study (12 patients), those who did not provide a urine sample for pneumococcal testing (114 patients), and those who resided outside the catchment areas (901 patients), the study population for this analysis comprised 2016 patients hospitalized for all-cause CAP (Figure 1). There were 1571 patients with blood cultures collected and 433 patients with cultures of respiratory or normally sterile compartment specimens. Among these patients, 279 (13.8%) had evidence of pneumococcal CAP including 150 identified by SSUAD assays only, 48 by S pneumoniae urinary antigen test only, 9 by blood or other cultures only, 36 by SSUAD and S pneumoniae urinary antigen test only, 14 by SSUAD and cultures only, 5 by S pneumoniae urinary antigen test and cultures only, and 17 by SSUAD, S pneumoniae urinary antigen test and cultures. Based on SSUAD assay results, a total of 198 patients (9.8%) had evidence of pneumococcal CAP caused by serotypes included in V116.
Figure 1. Flow Diagram for Identification of Study Population, 2018-2022.
SSUAD indicates serotype specific urinary antigen detection; V116, 21-valent pneumococcal conjugate vaccine.
The median (IQR) age of patients hospitalized for all-cause CAP was 60.1 (47.0-70.2) years; 726 patients (36.0%) were Black, 81 (4.0%) were Hispanic, and 1209 (60.0%) were White. By community setting, 1863 patients (92.4%) lived in a community dwelling, and 541 (27.7%) interacted with children aged 5 years old. The most common comorbidity was obesity (742 of 1963 patients [37.8%]), and the median (IQR) Charlson comorbidity index was 4.0 (2.0-6.0). A high admission CURB-65 score (defined as 3 or higher) was observed in 224 patients (11.1%). History of vaccination with pneumococcal polysaccharide or conjugate vaccines was 18.4% and 13.8%, respectively. Approximately two-thirds of patients (1340 [66.5%]) were enrolled in Tennessee. Characteristics of patients with pneumococcal CAP and with pneumococcal CAP due to serotypes included in V116 were generally similar to the larger group with all-cause CAP, although the proportion of patients with pneumococcal CAP who interacted with children under age 5 years was higher at 36.2% (98 of 271 patients) (Table 1).
Table 1. Characteristics of Adult Patients Hospitalized With Community-Acquired Pneumonia (CAP), 2018-2022.
| Characteristic | Patients, No. (%) | ||
|---|---|---|---|
| All-cause CAP (n = 2016) | Pneumococcal CAP, any serotype (n = 279) | Pneumococcal CAP with V116 serotype (n = 198) | |
| Age, median (IQR), y | 60.1 (47.0-70.2) | 60.0 (51.0-70.1) | 59.3 (50.3-68.5) |
| Age category, y | |||
| 18-49 | 597 (29.6) | 63 (22.6) | 49 (24.7) |
| 50-64 | 659 (32.7) | 118 (42.3) | 83 (41.9) |
| ≥65 | 760 (37.7) | 98 (35.1) | 66 (33.3) |
| Sex assigned at birth | |||
| Female | 929 (46.1) | 138 (49.5) | 89 (44.9) |
| Male | 1087 (53.9) | 141 (50.5) | 109 (55.1) |
| Race | |||
| American Indian or Native Alaskan | 10 (0.5) | 2 (0.7) | 2 (1.0) |
| Asian | 34 (1.7) | 1 (0.4) | 1 (0.5) |
| Black | 726 (36.0) | 136 (48.7) | 93 (47.0) |
| Native Hawaiian or Pacific Islander | 8 (0.4) | 2 (0.7) | 2 (1.0) |
| White | 1209 (60.0) | 136 (48.7) | 100 (50.5) |
| Other | 46 (2.3) | 4 (1.4) | 2 (1.0) |
| Ethnicity | |||
| Not Hispanic | 1870 (92.8) | 260 (93.2) | 186 (93.9) |
| Hispanic | 81 (4.0) | 12 (4.3) | 8 (4.0) |
| Unknown | 65 (3.2) | 7 (2.5) | 4 (2.0) |
| Type of home before illness | |||
| Community dwelling | 1863 (92.4) | 256 (91.8) | 183 (92.4) |
| Nursing home | 33 (1.6) | 3 (1.1) | 1 (0.5) |
| Assisted living | 31 (1.5) | 6 (2.2) | 3 (1.5) |
| Rehabilitation hospital | 10 (0.5) | 1 (0.4) | 1 (0.5) |
| School housing | 0 | 0 | 0 |
| Homeless or shelter residence | 44 (2.2) | 9 (3.2) | 7 (3.5) |
| Other | 21 (1.0) | 1 (0.4) | 1 (0.5) |
| Unknown | 14 (0.7) | 3 (1.1) | 2 (1.0) |
| Ever regularly smoked tobacco, No./total (%) | 987/2009 (49.1) | 162/278 (58.3) | 126/197 (64.0) |
| Alcohol use >3 d/wk, No./total (%) | 137/1999 (6.9) | 28/276 (10.1) | 21/196 (10.7) |
| Use of opioids at least weekly, No./total (%) | 331/1945 (17.0) | 52/270 (19.3) | 41/191 (21.5) |
| Interacts with child <5 y old at least once per wk, No./total (%) | 541/1954 (27.7) | 98/271 (36.2) | 70/192 (36.5) |
| Lives with children, No./total (%) | 427/1996 (21.4) | 67/275 (24.4) | 48/195 (24.6) |
| Received antibiotics for current illness before hospitalization, No./total (%) | 481/1848 (26.0) | 63/263 (24.0) | 46/188 (24.5) |
| Duration of acute illness prior to hospital admission, median (IQR), d | 2.7 (1.3, 5.7) | 2.8 (1.5-5.6) | 2.8 (1.5-5.5) |
| Charlson Comorbidity Index, median (IQR) | 4.0 (2.0-6.0) | 4.0 (2.0-6.0) | 4.0 (2.0-5.8) |
| Chronic medical conditions | |||
| Dementia | 64 (3.2) | 9 (3.2) | 2 (1.0) |
| COPD | 396 (19.6) | 77 (27.6) | 63 (31.8) |
| Asthma | 412 (20.4) | 61 (21.9) | 44 (22.2) |
| Heart failure | 341 (16.9) | 43 (15.4) | 31 (15.7) |
| Prior myocardial infarction | 173 (8.6) | 27 (9.7) | 18 (9.1) |
| Prior stroke | 210 (10.4) | 28 (10.0) | 16 (8.1) |
| End-stage kidney disease with chronic kidney replacement | 92 (4.6) | 10 (3.6) | 4 (2.0) |
| Diabetes | 513 (25.4) | 58 (20.8) | 37 (18.7) |
| Chronic liver disease | 141 (7.0) | 22 (7.9) | 14 (7.1) |
| Immunosuppression | 381 (18.9) | 54 (19.4) | 38 (19.2) |
| Solid organ cancer | 472 (23.4) | 66 (23.7) | 48 (24.2) |
| Hematologic cancer | 153 (7.6) | 24 (8.6) | 19 (9.6) |
| Solid organ transplant | 108 (5.4) | 12 (4.3) | 10 (5.1) |
| Pregnant | 14 (0.7) | 0 | 0 |
| Obesity (BMI >30), No./total (%) | 742/1963 (37.8) | 69/276 (25.0) | 45/195 (23.1) |
| CURB-65 score at admission | |||
| 0 | 717 (35.6) | 90 (32.3) | 68 (34.3) |
| 1 | 674 (33.4) | 105 (37.6) | 78 (39.4) |
| 2 | 401 (19.9) | 51 (18.3) | 33 (16.7) |
| 3 | 182 (9.0) | 26 (9.3) | 16 (8.1) |
| 4 | 40 (2.0) | 7 (2.5) | 3 (1.5) |
| 5 | 2 (0.1) | 0 | 0 |
| Timing of enrollment | |||
| Year 1 (September 2018-August 2019) | 694 (34.4) | 122 (43.7) | 79 (39.9) |
| Year 2 (September 2019-August 2020) | 560 (27.8) | 92 (33.0) | 72 (36.4) |
| Year 3 (November 2020-October 2021) | 411 (20.4) | 35 (12.5) | 24 (12.1) |
| Year 4 (November 2021-October 2022) | 351 (17.4) | 30 (10.8) | 23 (11.6) |
| SARS-CoV-2 test positive during the episode of pneumonia | 213 (10.6) | 11 (3.9) | 6 (3.0) |
| Location of enrollment | |||
| Tennessee | 1340 (66.5) | 148 (53.0) | 112 (56.6) |
| Georgia | 676 (33.5) | 131 (47.0) | 86 (43.4) |
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); COPD, chronic obstructive pulmonary disease; V116, 21-valent pneumococcal conjugate vaccine.
Incidence of Hospitalizations for All-Cause CAP
The overall estimated annual incidence of hospitalizations for all-cause CAP across the 4-year study period was 340 (95% CI, 323-358) per 100 000 adults (Figure 2, Table 2). The incidence of hospitalizations for all-cause CAP varied among study years, ranging from a high of 878 per 100 000 adults in year 2 (September 2019 to August 2020, which included the first year of the COVID-19 pandemic) to a low of 192 per 100 000 adults in year 4 (November 2021 to October 2022). Within each year, incidence consistently increased with increasing age. Excluding the second study year yielded an overall annual incidence of 282 (95% CI, 265-298) per 100 000 adults.
Figure 2. Population-Based Annual Incidence of Hospitalizations Community Acquired Pneumonia (CAP).
Incidence rates are presented by year and overall for the 4 study years combined. Column heights represent incidence point estimates; whiskers represent 95% CIs; V116, 21-valent pneumococcal conjugate vaccine.
Table 2. Population-Based Annual Incidence of Hospitalizations for Community-Acquired Pneumonia (CAP) Overall and by Study Years, 2018-2022a.
| Age group | Hospitalizations per 100 000 adult population/y (95% CI) | |||||||
|---|---|---|---|---|---|---|---|---|
| Year 1 (September 2018-August 2019) | Year 2 (September 2019-August 2020) | Year 3 (November 2020-October 2021) | Year 4 (November 2021-October 2022) | All years | ||||
| All-cause CAP | ||||||||
| 18-49 y | 99 (86-113) | 240 (202-279) | 119 (88-150) | 58 (43-72) | 107 (95-118) | |||
| 50-64 y | 384 (337-431) | 1073 (905-1242) | 445 (358-532) | 215 (172-258) | 417 (381-453) | |||
| ≥65 y | 1063 (937-1190) | 2888 (2419-3357) | 944 (788-1099) | 628 (530-726) | 1073 (991-1154) | |||
| All adults | 322 (298-347) | 878 (788-969) | 334 (296-372) | 192 (170-213) | 340 (323-358) | |||
| Pneumococcal CAP (regardless of serotype) | ||||||||
| 18-49 y | 11 (9-12) | 28 (23-32) | 16 (11-22) | 5 (4-7) | 11 (9-13) | |||
| 50-64 y | 85 (75-96) | 179 (151-207) | 55 (40-70) | 28 (22-33) | 66 (60-72) | |||
| ≥65 y | 187 (165-210) | 225 (189-262) | 83 (69-97) | 58 (47-68) | 117 (108-126) | |||
| All adults | 57 (52-61) | 96 (87-106) | 37 (31-42) | 20 (17-22) | 42 (39-44) | |||
| V116 serotype pneumococcal CAP | ||||||||
| 18-49 y | 8 (7-9) | 24 (20-27) | 13 (8-18) | 4 (3-5) | 10 (8-11) | |||
| 50-64 y | 59 (52-66) | 154 (130-179) | 31 (21-41) | 23 (18-27) | 49 (44-53) | |||
| ≥65 y | 118 (104-133) | 135 (114-157) | 65 (55-74) | 36 (31-41) | 78 (72-84) | |||
| All adults | 38 (35-41) | 73 (66-80) | 26 (22-30) | 14 (12-16) | 30 (29-32) | |||
Year 2 estimates were derived from Vanderbilt only due to local restrictions in Georgia during the initial period of the COVID-19 pandemic.
Incidence of Hospitalizations for Pneumococcal CAP and Pneumococcal CAP Due to Serotypes in V116
The overall annual incidence of hospitalizations for pneumococcal CAP and pneumococcal CAP due to serotypes in V116 was 43 (95% CI, 41-46) and 30 (95% CI, 29-32) per 100 000 adults, respectively. Similar to the incidence of hospitalizations for all-cause CAP and the incidence of pneumococcal CAP and pneumococcal CAP caused by V116 serotypes was highest during year 2 and lowest during year 4. The incidence of hospitalizations for pneumococcal CAP and pneumococcal CAP caused by V116 serotypes generally increased with increasing age (Table 2). Excluding the second study year, the annual incidence of pneumococcal CAP and pneumococcal CAP caused by V116 serotypes were 37 (95% CI, 35-40) and 26 (95% CI, 24-27) per 100 000 adults, respectively. Additional details about annual incidence estimates by enrolling site are provided in eTable 3 in Supplement 1.
Distribution of Detected Pneumococcal Serotypes
Information on the distribution of pneumococcal serotypes in the overall PNEUMO study population has been previously published.6 Among patients hospitalized with CAP from prespecified catchment areas for the current incidence calculations, detection of pneumococcal serotypes by SSUAD testing was highest in year 1 with 100 pneumococcal serotypes detected, and lowest during year 4 with 28 serotypes detected. The pneumococcal serotype detections in the most recent study year (year 4) included: 12 detections of serotypes included in PCV15, PCV20, and V116; 4 detections of serotypes not included in V116; 4 detections of serotypes included in both PCV20 and V116; and 8 detections of serotypes included in V116 but not in PCV15 or PCV20 (Table 3; eTable 4 in Supplement 1).
Table 3. Counts of Pneumococcal Serotypes Detected by Serotype Specific Urinary Antigen Detection (SSUAD) by Year of Enrollment, 2018-2022a.
| Pneumococcal serotype | Year 1 (September 2018-August 2019) (n = 100) | Year 2 (September 2019-August 2020) (n = 85) | Year 3 (November 2020-October 2021) (n = 30) | Year 4 (November 2021-October 2022) (n = 28) |
|---|---|---|---|---|
| PCV15, PCV20, and V116 conjugate vaccine | ||||
| 3 | 13 (13.0) | 17 (20.0) | 2 (6.7) | 4 (14.3) |
| 6A | 0 | 0 | 3 (10.0) | 4 (14.3) |
| 7F | 3 (3.0) | 2 (2.4) | 1 (3.3) | 1 (3.6) |
| 19A | 5 (5.0) | 7 (8.2) | 3 (10.0) | 3 (10.7) |
| 22F | 15 (15.0) | 5 (5.9) | 0 | 0 |
| 33F | 2 (2.0) | 0 | 2 (6.7) | 0 |
| PCV15 and PCV20 (not V116) conjugate vaccine | ||||
| 1 | 6 (6.0) | 1 (1.2) | 0 | 0 |
| 4 | 0 | 0 | 1 (3.3) | 1 (3.6) |
| 5 | 2 (2.0) | 2 (2.4) | 0 | 0 |
| 6B | 0 | 1 (1.2) | 1 (3.3) | 0 |
| 9V | 1 (1.0) | 1 (1.2) | 2 (6.7) | 2 (7.1) |
| 14 | 0 | 0 | 0 | 0 |
| 18C | 0 | 0 | 0 | 0 |
| 19F | 9 (9.0) | 5 (5.9) | 0 | 1 (3.6) |
| 23F | 0 | 0 | 0 | 0 |
| PCV20 and V116 (not PCV15) conjugate vaccine | ||||
| 8 | 1 (1.0) | 4 (4.7) | 1 (3.3) | 1 (3.6) |
| 10A | 1 (1.0) | 0 | 0 | 0 |
| 11A | 8 (8.0) | 2 (2.4) | 1 (3.3) | 3 (10.7) |
| 12F | 0 | 1 (1.2) | 0 | 0 |
| V116 only (not PCV15 or PCV20) conjugate vaccine | ||||
| 9N | 4 (4.0) | 5 (5.9) | 1 (3.3) | 4 (14.3) |
| 15A | 3 (3.0) | 0 | 0 | 0 |
| 15C | 1 (1.0) | 1 (1.2) | 1 (3.3) | 0 |
| 16F | 3 (3.0) | 4 (4.7) | 1 (3.3) | 0 |
| 17F | 0 | 5 (5.9) | 3 (10.0) | 1 (3.6) |
| 20 | 5 (5.0) | 3 (3.5) | 0 | 0 |
| 23A | 4 (4.0) | 4 (4.7) | 2 (6.7) | 0 |
| 23B | 4 (4.0) | 3 (3.5) | 1 (3.3) | 2 (7.1) |
| 24F | 1 (1.0) | 0 | 0 | 0 |
| 31 | 5 (5.0) | 3 (3.5) | 0 | 1 (3.6) |
| 35B | 4 (4.0) | 9 (10.6) | 4 (13.3) | 0 |
Abbreviation: PCV, pneumococcal conjugate vaccine.
SSUAD assays used in this study are able to detect 30 distinct pneumococcal serotypes (eTable 1 in Supplement 1). A total of 243 pneumococcal serotypes were detected in 217 unique patients. Serotype 15B is contained in PCV20 but is not among the 30 serotypes covered by the SSUAD assays. Serotypes included in V116 (PCV21): 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, 35B. Serotypes included in PCV20: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 18C, 19A, 19F, 22F, 23F, 33F. Serotypes included in PCV15: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F.
Discussion
In this multicenter, prospective, active surveillance study we estimated an annual incidence of 340 hospitalizations for CAP per 100 000 adults, which is within the range of estimates from previous prospective studies conducted prior to the COVID pandemic.5,18 Approximately 14% of hospitalizations for CAP had evidence of S pneumoniae infection, and the majority of those pneumococcal detections corresponded to serotypes included in the newly licensed V116 vaccine, which was not commercially available during the study period. The incidence of hospitalizations for CAP and pneumococcal pneumonia increased substantially with age.
The study period included 4 consecutive years of surveillance and encompassed the beginning of the COVID-19 pandemic, a period with major disruptions in regular societal activities, alterations in the circulation of common respiratory pathogens,19,20,21 and a substantial impact on health care systems worldwide. The impact of the initial pandemic waves and the implementation of social distancing policies varied among enrolling sites. As the pandemic evolved, circulation of respiratory pathogens has started returning to their prepandemic circulation patterns. Nevertheless, the project maintained active surveillance while navigating the development and evolution of the pandemic and the measures implemented as part of the response.
The overall estimated annual incidence rate for all-cause CAP hospitalizations of 340 per 100 000 adults is within the range of previous similar studies that estimated the incidence of hospitalizations for CAP.22 A large multicenter prospective study of hospitalizations of adults with CAP conducted from 2010 through 2012, following the introduction of PCV13 for children in 2010, reported an overall annual incidence of 248 per 100 000 adults.5 A similar prospective study conducted at multiple hospitals in a defined catchment area between 2014 and 2016 reported an overall annual incidence of 634 hospitalizations for CAP per 100 000 adults.18 A previous systematic review of incidence of hospitalizations for CAP found a wide range of reported estimates, with variation depending on the study design and selection criteria, including which types of pneumonia episodes were included. The vast majority of studies included in the review were based on retrospective examination of claims or hospitalization records, whereas prospectively conducted studies were infrequent.22 The current study complements previous reports and provides a rigorous estimate of the incidence of CAP hospitalizations during and following the onset of the COVID-19 pandemic.
Results of this study demonstrate that pneumococcal CAP remains an important cause of hospitalizations in the US. The annual incidence rate of 43 hospitalizations per 100 000 adults estimated in this study extrapolates to approximately 114 800 US adult hospitalizations for pneumococcal CAP each year based on current population estimates. With vaccination as the primary preventive measure for pneumococcal pneumonia, improved pneumococcal vaccines with appropriate vaccination coverage could lessen the burden of severe pneumonia on the US population, especially among older adults.
The identification of hospitalizations for pneumococcal pneumonia in this study benefitted from the use of serotype-specific urinary antigen detection assays that covered 30 distinct pneumococcal serotypes. This and similar research diagnostic tools have facilitated the detection of pneumococcal serotypes in recent CAP studies in adult populations.6,7,13,14,15,23,24,25,26,27 Nevertheless, additional work is needed to systematically reconcile pneumococcal detections from these novel assays with those from other tests including non–serotype-specific urinary antigen detection tests and cultures.6,13,14
Limitations
Our study findings need to be interpreted in light of several limitations. First, there was variability in incidence estimates between enrollment sites and across the study years. While the COVID-19 pandemic and the response to the pandemic likely played a partial role in the variations in hospitalizations for CAP and pneumococcal pneumonia over time,19,20,21 specific reasons for the differences in disease incidence observed between enrollment sites, including potential changes in recruitment activities or changes in health care seeking behaviors in the underlying populations,20,28 require additional examination. Second, incidence calculations were derived from enrollments performed at surveillance hospitals in large catchment areas and required assumptions about similarity of patients and hospitalizations between enrollment hospitals and other hospitals that provided health care to residents in the catchment areas. Third, determining the etiology of pneumonia remains challenging and the majority of adult pneumonias do not have a clear etiology determined. Although the project implemented systematic testing using novel urinary assays that allow detection of pneumococcal etiology through detection of a large number of specific pneumococcal serotypes, the assays did not cover all serotypes so the representation of pneumococcal etiology among patients with pneumonia remains incomplete. Furthermore, while available cultures of lower respiratory tract specimens and blood were included in the assessment of pneumococcal etiology overall, those were not included in serotype specific analyses. Few blood cultures could be serotyped and other positive cultures were not serotyped. Of note, when isolates were obtained and serotyped from blood cultures, those detections had a very high agreement with those from urinary assay detections.6 Finally, the study was conducted at large hospitals in urban centers in 2 US states with patients representing certain demographic, immunization and medical characteristics. Moreover, not all screened and eligible patients agreed to participate and enrolled in the study. Thus, extrapolation of our findings to other settings or populations needs to consider this potential caveat.
Conclusions
In this large prospective study, we demonstrated that there is a large remaining burden of hospitalizations for CAP among US adults, with the highest burden of disease among adults age 65 years or older. About 14% of CAP was still caused by S pneumoniae, especially by those serotypes included in V116.
eMethods.
eTable 1. 30 Pneumococcal Serotypes Detected by Serotype Specific Urinary Antigen Detection (SSUAD) Assays Used in This Study and Serotypes Contained in V116
eTable 2. ICD-10 Codes Used to Define Acute Respiratory Illness in This Study
eTable 3. Population-Based Annual Incidence of Hospitalizations for Community-Acquired Pneumonia by Site and Study Years, PNEUMO Study, Tennessee and Georgia, 2018-2022
eTable 4. Counts of Pneumococcal Serotypes Detected by Serotype Specific Urinary Antigen Detection (SSUAD) by Site and Year of Enrollment Among Residents in Geographic Catchment Areas Used for Incidence Calculations, PNEUMO Study, Tennessee and Georgia, 2018-2022
Nonauthor Collaborators
Data Sharing Statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eMethods.
eTable 1. 30 Pneumococcal Serotypes Detected by Serotype Specific Urinary Antigen Detection (SSUAD) Assays Used in This Study and Serotypes Contained in V116
eTable 2. ICD-10 Codes Used to Define Acute Respiratory Illness in This Study
eTable 3. Population-Based Annual Incidence of Hospitalizations for Community-Acquired Pneumonia by Site and Study Years, PNEUMO Study, Tennessee and Georgia, 2018-2022
eTable 4. Counts of Pneumococcal Serotypes Detected by Serotype Specific Urinary Antigen Detection (SSUAD) by Site and Year of Enrollment Among Residents in Geographic Catchment Areas Used for Incidence Calculations, PNEUMO Study, Tennessee and Georgia, 2018-2022
Nonauthor Collaborators
Data Sharing Statement
