Incidence of respiratory syncytial virus and influenza: A Danish nationwide cohort study

ABSTRACT

Respiratory syncytial virus (RSV) is, like influenza, one of the most common causes of severe acute respiratory infections (ARIs) in adults; however, its incidence across different risk and age groups is unknown. We estimated the incidence of registered ARIs in Danish adults, focusing on RSV and contextualizing with influenza. We conducted a nationwide cohort study in Denmark, including all adults aged ≥18 y with a registered ARI, during the 2011/12 to 2022/23 seasons. We estimated the incidence (per 100,000 person-years) of ARI overall and ARI attributable to RSV or influenza, overall and stratified by sex, age, and comorbidity. We identified 962,858 ARIs, of which 10,437 (1.1%) were attributed to RSV and 62,869 (6.5%) to influenza. The ARI incidence increased over time (range: 1,272–2,144), including a rise in RSV incidence (range: 0.2–91.6), while influenza incidence fluctuated (range: 6.7–322.0). In the 2022/23 season, RSV incidence was higher among females, older adults (198.7 in ≥60-y-olds, and 303.2 in ≥75-y-olds), and those with comorbidities, especially hematologic disease (868.6) and chronic obstructive pulmonary disease (679.5). Although influenza incidence was generally higher than RSV, the incidences were comparable for older adults and those with comorbidities. In conclusion, RSV is an important cause of ARIs among adults, comparable to influenza, particularly in older adults and those with comorbidities. These findings underscore the substantial burden of RSV that is relevant for public health planning and clinical decision-making, particularly given the recent approval of three highly effective RSV vaccines.

GRAPHICAL ABSTRACT

Introduction

Respiratory syncytial virus (RSV) is a common virus that causes acute respiratory infections (ARIs) in both children and adults.^1,2 The clinical presentation of RSV can range from mild upper respiratory tract disease (URTD) to severe lower respiratory tract disease (LRTD), which can cause acute respiratory failure. The most vulnerable groups for severe RSV include children under 5 y, older adults, and those with comorbidities.^3,4 Like RSV, influenza is a common virus that causes ARIs in both children and adults, with similar clinical presentations and high-risk groups.^5,6

Globally, RSV incidence in adults appears to vary substantially.⁷ A meta-analysis of over 11,000 cases of laboratory-confirmed RSV-associated ARIs found a worldwide incidence of 37.6 per 1,000 persons per year among adults with comorbidities, mostly based on prospective studies,⁸ while another meta-analysis reported an incidence of 6.7 per 1,000 persons per year in adults aged ≥ 65 y from the general population.⁹ A comprehensive review of observational studies concluded that RSV incidence varies substantially per study and increases with age, with the highest incidences seen in older adults with comorbidities. In three European countries included, RSV incidence during the 2018/19 season was 4.9%, with 67% of patients with RSV having comorbidities.⁷ Incidence estimates for adults in Denmark are not available.

The understanding of the burden of RSV in adults is increasingly critical, especially as three vaccines – AREXVY, ABRYSVO, and mRESVIA – have been approved for use in adults by the United States (US) Food and Drug Administration and the European Medicines Agency.^10–12 RSV vaccines are not yet included in Denmark’s national vaccination program for adults. Instead, adults must purchase them at their own expense.¹³ Only for individuals ≥ 60 y old with chronic obstructive pulmonary disease (COPD) has AREXVY been provided with conditional reimbursement since August 2024, and ABRYSVO since August 2025.¹⁴ In contrast, influenza vaccines are fully reimbursed for high-risk groups, such as those aged ≥ 65 y and those with specific comorbidities or immunodeficiencies.¹⁵

This study aimed to estimate the incidence of ARIs in Danish adults over the past decade, with a primary focus on RSV, contextualizing with influenza. For this purpose, we used a nationwide study design covering the whole adult population to determine the incidence of registered RSV episodes among the general adult population, and also among high-risk groups such as older adults and those with comorbidities.

Methods

Study design and data sources

This study analyzed nationwide data by linking different national registers in Denmark (see Supplemental Methods).

Subjects

All adults aged ≥ 18 y in Denmark with an ARI-specific International Classification of Diseases, 10th Revision (ICD-10) hospitalization code (Supplemental Table S1) or positive microbiological test result (Supplemental Table S2) from 1 July 2011 to 30 June 2023 were included. Individuals without a Danish personal identification number (Central Person Registration) were excluded. The unit for calculating ARIs was episodes (not individuals). An ARI was defined as an ARI episode, i.e., a single event or a series of events within 28 d of the first event. A person could have multiple ARIs during the 12-season study period. All ARIs were included, irrespective of the cause, and were classified as overall ARI, RSV when the causal agent was RSV, influenza when the causal agent was influenza, ARIs caused by other specific pathogens, or unspecified ARIs.

Variables and statistical analysis

Comorbidities were assessed in the 10 y preceding the ARI and included diabetes, chronic heart failure (CHF), immunocompromised status (for ICD-10 codes see Supplemental Table S3), major adverse cardiovascular events (MACE), asthma, COPD, hematologic disease, any other chronic respiratory disease (CRD), rheumatological disease, advanced liver disease, and chronic renal disease. Annual and monthly ARI incidences were calculated by dividing the number of ARI episodes in each year or month by the number of person-years (PY) or person-months at risk and presented per 100,000 PY. For each incidence rate, the 95% confidence interval (CI) was computed using exact Poisson confidence limits based on chi‑square distributions for the observed event counts and person‑time. Seasons spanned from 1 July to 30 June. The ARI incidences were stratified based on sex, age, comorbidities, causal agent, and localization (URTD or LRTD) and were calculated by dividing the number of ARI episodes in each year for each stratification variable by the appropriate number of PY at risk for that stratification variable. Additional analyses can be found in the Supplemental Methods. Data were analyzed using RStudio.

Results

Over the 12 seasons from 2011/12 to 2022/23, based on ICD-10 codes or Danish Microbiology Database (MiBa) tests, 962,858 ARI cases were identified, of which 10,437 (1.1%) were attributed to RSV and 62,869 (6.5%) to influenza.

Annual ARI incidence

The overall ARI incidence across the 12 seasons varied from 1,272 (95 % CI: 1,263–1,280) to 2,144 (95 % CI: 2,133–2,156) per 100,000 PY, with a tendency toward an increase over time, except for a drop to 1,272 (95 % CI: 1,263–1,280) in the 2020/21 season during the coronavirus disease 2019 (COVID-19) pandemic, followed by a sharp increase in the 2021/22 and 2022/23 seasons. RSV incidence also increased over time, especially from season 2017/18 and onwards, and peaked at 91.6 (95 % CI: 89.3–93.9) per 100,000 PY in the last season analyzed (2022/23). Influenza incidence fluctuated across seasons, with peaks of 322.0 (95 % CI: 317.7–326.4) per 100,000 PY in season 2017/18 and 251.1 (95 % CI: 247.3–254.9) in season 2021/22. Like overall ARI, a large drop in RSV and influenza incidences was observed in the 2020/21 season during the COVID-19 pandemic. For COVID-19, only hospital-coded cases were included, which explains the lack of an increase in overall ARI during the COVID-19 pandemic. ARIs caused by other pathogens had a relatively stable incidence from seasons 2011/12 to 2018/19, with an increase thereafter (when severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] was included in this group), while the incidence of unspecified ARIs remained relatively stable over all seasons (Table 1).

Table 1.

Number and incidence of overall ARI, RSV-ARI, influenza-ARI, ARI caused by other pathogens, and unspecified ARI across seasons.

	Season
	2011/ 12	2012/ 13	2013/ 14	2014/ 15	2015/ 16	2016/ 17	2017/ 18	2018/ 19	2019/ 20	2020/ 21	2021/ 22	2022/ 23
Overall RSV
Total number	58,425	62,122	67,609	87,461	85,453	87,590	98,889	85,858	76,326	59,566	94,951	98,608
Incidence  (95% CI)	1,335.5 (1,326.4–1,344.6)	1,409.5 (1,400.2–1,418.9)	1,521.1 (1,511.5–1,530.8)	1,949.8 (1,939.0–1,960.7)	1,884.8 (1,874.2–1,895.5)	1,914.1 (1,903.5–1,924.8)	2,144.4 (2,133.2–2,155.6)	1,849.3 (1,838.9–1,859.7)	1,635.7 (1,625.9–1,645.4)	1,271.8 (1,263.3–1,280.4)	2,012.8 (2,002.1–2,023.6)	2,066.3 (2,055.5–2,077.2)
RSV-ARI
Total number	17	71	37	103	166	321	1,310	1,082	936	10	2,012	4,372
Incidence  (95% CI)	0.4 (0.2–0.6)	1.6 (1.3–2.0)	0.8 (0.6–1.1)	2.3 (1.9–2.7)	3.7 (3.2–4.2)	7.0 (6.4–7.7)	28.4 (27.1–29.7)	23.3 (22.2–24.5)	20.1 (19.0–21.2)	0.2 (0.1–0.4)	42.7 (41.1–44.2)	91.6 (89.3–93.9)
Influenza-ARI
Total number	723	1,582	1,208	2,302	2,982	3,359	14,850	9,703	5,231	316	11,844	8,769
Incidence  (95% CI)	16.5 (15.5–17.6)	35.9 (34.4–37.4)	27.2 (25.9–28.5)	51.3 (49.6–53.1)	65.8 (63.8–67.8)	73.4 (71.3–75.5)	322.0 (317.7–326.4)	209.0 (205.5–212.5)	112.1 (109.6–114.7)	6.7 (6.1–7.4)	251.1 (247.3–254.9)	183.8 (180.5–187.0)
ARI caused by other pathogens
Total number	6,378	5,098	4,647	4,974	5,053	4,845	4,522	3,690	5,788	12,404	22,880	16,167
Incidence  (95% CI)	145.8 (142.8–148.8)	115.7 (113.0–118.4)	104.6 (102.0–107.1)	110.9 (108.3–113.5)	111.5 (108.9–114.1)	105.9 (103.4–108.4)	98.1 (95.7–100.5)	79.5 (77.3–81.7)	124.0 (121.4–126.8)	264.8 (260.9–268.8)	485.0 (479.8–490.3)	338.8 (334.4–343.2)
Unspecified ARI
Total number	51,307	55,371	61,717	80,082	77,252	79,065	78,207	71,383	64,371	46,836	58,215	69,300
Incidence (95% CI)	1,172.8 (1,164.3–1,181.3)	1,256.3 (1,247.6–1,265.2)	1,388.5 (1,379.4–1,397.8)	1,785.3 (1,775.0–1,795.7)	1,703.9 (1,693.9–1,714.1)	1,727.8 (1,717.7–1,737.9)	1,695.9 (1,685.9–1,705.9)	1,537.5 (1,528.1–1,547.0)	1,379.5 (1,370.5–1,388.5)	1,000.0 (992.4–1,007.7)	1,234.1 (1,225.7–1,242.5)	1,452.2 (1,443.1–1,461.3)

The incidence is presented per 100,000 person-years. ARI was based on an ARI-specific ICD-10 hospitalization code or positive microbiological test result. The 95% confidence intervals for incidence rates were computed using exact Poisson confidence limits based on chi‑square distributions for the observed event counts and person‑time.

ARI, acute respiratory infection; CI, confidence interval; ICD-10, International Classification of Diseases, 10th Revision; RSV, respiratory syncytial virus.

RSV and influenza monthly incidences

The monthly incidences for the seasons 2017/18 to 2022/23 for RSV and influenza are displayed in Figure 1. RSV incidence peaked in January to March in the seasons 2017/18 to 2019/20, while it peaked in October to December in seasons 2021/22 to 2022/23 (Figure 1(A)). Influenza incidence peaked in February to March in seasons 2017/18 to 2021/22, and in December in season 2022/23 (Figure 1(B)).

Figure 1.

Incidence of RSV and influenza per month per season, considering the most recent seasons (2017/18 to 2022/23).

The incidence per season (per 100,000 person-years) for (A) RSV, and (B) influenza. Please note the scale difference of the y-axes. The 2020/2021 season has been omitted as there was a significant drop in RSV and influenza incidences due to the COVID-19 pandemic and the accompanying lockdowns and social distancing.

COVID-19, coronavirus disease 2019; RSV, respiratory syncytial virus.

RSV and influenza among different groups

In all seasons, using the incidences (per 100,000 PY) of the 2022/23 season as an example, RSV incidence was slightly higher among females than males (103.9 [95 % CI: 100.6–107.4] vs 78.9 [95 % CI: 76.0–82.0]) and increased with age (30.6 [95 % CI: 28.8–32.5] in those aged 18–49 y, 64.2 [95 % CI: 59.6–69.0] in 50–59 y, 198.7 [95 % CI: 192.9–204.7] in ≥60 y, and 303.2 [95 % CI: 291.5–315.3] in those aged ≥ 75 y). RSV incidence was also higher among individuals with comorbidities, especially hematologic disease (868.6 [95 % CI: 798.0–944.0]), COPD (679.5 [95 % CI: 646.0–714.3]), and any other CRD (319.1 [95 % CI: 289.7–350.8]) (Table 2 and Figure 2).

Table 2.

Number and incidence of RSV among different groups across seasons.

		Season
Groups		2011/ 12	2012/ 13	2013/ 14	2014/ 15	2015/ 16	2016/ 17	2017/ 18	2018/ 19	2019/ 20	2020/ 21	2021/ 22	2022/ 23
Sex
Male	Number	10	37	11	49	75	160	566	475	388	<5	837	1,858
	Incidence (95% CI)	0.5 (0.3–0.8)	1.7 (1.3–2.2)	0.5 (0.3–0.8)	2.2 (1.7–2.8)	3.4 (2.7–4.1)	7.1 (6.2–8.1)	24.9 (23.2–26.6)	20.7 (19.2–22.4)	16.8 (15.5–18.3)	–	35.9 (33.9–38.0)	78.9 (76.0–82.0)
Female	Number	7	34	26	54	91	161	744	607	548	<5	1,175	2,514
	Incidence (95% CI)	0.3 (0.1–0.6)	1.5 (1.1–2.0)	1.2 (0.8–1.6)	2.4 (1.9–3.0)	4.0 (3.3–4.7)	6.9 (6.1–7.9)	31.9 (30.0–33.9)	25.8 (24.1–27.6)	23.2 (21.6–24.9)	–	49.2 (46.9–51.6)	103.9 (100.6–107.4)
Age
18–49 y	Number	<5	24	<5	23	30	69	319	265	266	<5	583	732
	Incidence (95% CI)	–	1.0 (0.7–1.4)	–	1.0 (0.7–1.4)	1.3 (0.9–1.7)	2.9 (2.4–3.6)	13.5 (12.3–14.8)	11.2 (10.1–12.4)	11.2 (10.1–12.4)	–	24.6 (23.0–26.4)	30.6 (28.8–32.5)
50–59 y	Number	<5	17	<5	21	22	48	177	160	123	<5	303	521
	Incidence (95% CI)	–	2.3 (1.5–3.5)	–	2.8 (1.9–4.0)	2.9 (2.0–4.1)	6.2 (4.8–7.8)	22.4 (19.7–25.3)	20.1 (17.5–22.9)	15.4 (13.2–17.9)	–	37.6 (34.1–41.4)	64.2 (59.6–69.0)
≥50 y	Number	<5	47	24	80	136	252	991	817	670	<5	1,429	3,640
	Incidence (95% CI)	–	2.3 (1.8–2.9)	1.1 (0.8–1.6)	3.7 (3.1–4.5)	6.3 (5.4–7.2)	11.4 (10.2–12.6)	44.1 (41.8–46.5)	35.9 (33.9–38.1)	29.2 (27.3–31.1)	–	60.8 (58.2–63.5)	152.9 (148.7–157.1)
≥60 y	Number	8	30	20	59	114	204	814	657	547	6	1,126	3,119
	Incidence (95% CI)	0.6 (0.3–1.1)	2.2 (1.6–3.0)	1.5 (1.0–2.1)	4.3 (3.4–5.3)	8.1 (6.9–9.5)	14.2 (12.6–16.0)	56.0 (52.8–59.3)	44.5 (41.7–47.5)	36.5 (34.0–39.2)	0.4 (0.2–0.8)	72.9 (69.4–76.6)	198.7 (192.9–204.7)
≥65 y	Number	6	27	11	52	96	179	716	553	462	5.0	972	2,703
	Incidence (95% CI)	0.6 (0.3–1.2)	2.7 (1.9–3.7)	1.1 (0.6–1.8)	5.0 (3.9–6.2)	9.0 (7.5–10.6)	16.4 (14.4–18.5)	64.3 (60.4–68.4)	48.8 (45.4–52.3)	40.0 (37.0–43.2)	0.4 (0.2–0.9)	81.4 (77.2–85.9)	223.0 (216.0–230.2)
≥75 y	Number	<5	12	6	24	45	100	415	311	255	<5	601	1,781
	Incidence (95% CI)	–	3.0 (1.7–4.8)	1.4 (0.6–2.9)	5.7 (3.9–7.9)	10.3 (7.9–13.2)	22.3 (18.7–26.3)	89.1 (82.0–96.6)	64.1 (58.2–70.4)	50.0 (45.0–55.5)	–	106.6 (99.6–114.0)	303.2 (291.5–315.3)
Comorbidities
Diabetes	Number	8	12	<5	6	18	44	191	135	123	<5	257	605
	Incidence (95% CI)	3.8 (1.9–6.9)	5.3 (3.1–8.6)	–	2.5 (1.1–4.9)	7.2 (4.7–10.7)	17.2 (13.2–22.1)	72.7 (64.3–82.0)	50.3 (43.4–58.0)	45.0 (38.5–52.2)	–	89.6 (80.6–99.4)	204.7 (191.2–219.0)
CHF	Number	0	<5	<5	<5	10	10	41	30	21	0	42	84
	Incidence (95% CI)	0.0 (0.0–2.2)	–	–	–	7.5 (4.0–12.7)	7.5 (4.1–12.7)	30.6 (23.2–39.7)	22.4 (16.1–30.4)	15.8 (10.6–22.7)	0.0 (0.0–2.2)	31.4 (23.8–40.6)	62.3 (51.6–74.7)
Immunocompromised status	Number	5	36	15	49	69	163	435	375	307	5	598	1,354
	Incidence (95% CI)	1.1 (0.4–2.4)	7.8 (5.8–10.3)	3.1 (1.9–4.8)	9.9 (7.7–12.6)	13.5 (11.0–16.5)	30.9 (27.0–35.2)	80.0 (73.8–86.6)	67.6 (62.0–73.6)	54.6 (49.6–60.0)	0.9 (0.3–1.8)	102.6 (95.8–109.7)	229.1 (218.9–239.6)
MACE	Number	<5	9	<5	8	13	40	145	101	80	<5	148	417
	Incidence (95% CI)	–	4.3 (2.3–7.6)	–	3.8 (1.9–6.9)	6.2 (3.6–9.8)	18.8 (14.2–24.4)	67.6 (58.6–77.6)	46.7 (39.4–55.1)	36.9 (30.4–44.5)	–	67.3 (58.5–77.1)	189.1 (174.1–205.1)
Asthma	Number	<5	6	7	12	11	26	140	121	121	<5	295	523
	Incidence (95% CI)	–	1.8 (0.8–3.6)	2.1 (1.0–3.9)	3.6 (2.1–5.8)	3.3 (1.8–5.4)	7.7 (5.4–10.6)	41.2 (35.6–47.4)	35.5 (30.4–41.3)	35.3 (30.2–41.0)	–	84.0 (76.1–92.5)	147.3 (136.8–158.3)
COPD	Number	6	15	8	29	59	96	321	253	214	<5	412	1,091
	Incidence (95% CI)	5.1 (2.2–10.2)	12.1 (7.4–18.6)	6.1 (3.0–11.0)	21.1 (15.1–28.8)	40.9 (32.5–50.8)	63.6 (53.3–75.3)	205.9 (187.3–225.8)	158.5 (142.5–175.9)	131.6 (117.1–147.3)	–	253.9 (233.7–275.5)	679.5 (646.0–714.3)
Hematologic disease	Number	<5	20	11	32	25	90	171	145	105	<5	193	395
	Incidence (95% CI)	–	62.7 (41.5–91.1)	33.2 (18.6–55.0)	93.0 (67.7–124.9)	69.5 (48.3–97.0)	237.9 (198.2–283.5)	439.1 (385.4–498.5)	362.9 (314.8–416.5)	256.2 (216.5–301.2)	–	437.5 (387.0–493.0)	868.6 (798.0–944.0)
Any other CRD	Number	0	<5	<5	11	22	40	104	99	69	<5	123	306
	Incidence (95% CI)	0.0 (0.0–5.0)	–	–	15.1 (8.5–25.1)	28.3 (19.1–40.3)	48.3 (36.5–62.9)	119.9 (101.2–141.1)	109.2 (91.8–129.0)	74.2 (60.1–90.6)	–	128.9 (110.4–149.7)	319.1 (289.7–350.8)
Rheumatological disease	Number	<5	<5	<5	<5	<5	15	39	28	29	<5	44	97
	Incidence (95% CI)	–	–	–	–	–	29.3 (18.1–45.2)	74.5 (56.0–97.3)	52.6 (37.4–72.1)	54.2 (38.7–73.8)	–	81.5 (62.4–104.8)	179.7 (150.8–212.8)
Advanced liver disease	Number	<5	0	0	<5	6	9	30	21	20	0	37	65
	Incidence (95% CI)	–	0.0 (0.0–6.7)	0.0 (0.0–6.5)	–	12.5 (5.4–24.7)	18.4 (9.6–32.0)	60.0 (43.2–81.4)	41.6 (27.9–59.9)	39.5 (26.2–57.4)	0.0 (0.0–5.9)	72.1 (53.8–94.9)	126.5 (101.9–155.5)
Chronic renal disease	Number	<5	12	<5	9	16	36	73	46	63	<5	124	285
	Incidence (95% CI)	–	17.2 (9.9–27.8)	–	11.4 (6.0–20.0)	19.3 (12.1–29.3)	41.2 (30.6–54.4)	80.0 (65.2–97.2)	48.7 (37.5–62.3)	65.3 (52.4–80.6)	–	126.5 (108.4–146.9)	290.4 (262.7–320.3)

The incidence is presented per 100,000 person-years.

The absolute number of ARI episodes and the incidence within a subgroup were omitted if the number of ARI episodes was < 5.

The 95% confidence intervals for incidence rates were computed using exact Poisson confidence limits based on chi‑square distributions for the observed event counts and person‑time.

ARI, acute respiratory infection; CHF, chronic heart failure; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CRD, chronic respiratory disease; MACE, major adverse cardiovascular events; RSV, respiratory syncytial virus; –, not applicable.

Figure 2.

Incidence of RSV and influenza for the most recent season (2022/2023) among different subgroups.

The incidence (per 100,000 person-years) in the 2022/2023 season for RSV and influenza.

CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; CRD, chronic respiratory disease; MACE, major adverse cardiovascular events; RSV, respiratory syncytial virus.

Like RSV, influenza incidence was higher in females, increased with age, and was higher among those with comorbidities, especially COPD (804.7 [95 % CI: 768.2–842.5]), hematologic disease (686.1 [95 % CI: 623.5–753.5]), and any other CRD (430.7 [95 % CI: 396.4–467.2]) (Supplemental Table S4 and Figure 2).

The incidence of RSV was generally lower than that of influenza, which was observed across all seasons and also when comparing the different subgroups. However, in the last season included in the study (i.e., 2022/23), these incidences were comparable in many of the subgroups, especially among individuals aged ≥ 65 y and those living with specific comorbidities. For example, in the 2022/23 season, incidence among individuals aged ≥ 75-y-olds was 303.2 (95 % CI: 291.5–315.3) for RSV and 303.7 (95 % CI: 292.0–315.8) for influenza (Table 2, Supplemental Table S4, and Figure 2).

Overall ARI LRTD and URTD among different groups

When considering the incidence of overall ARI per localization (LRTD vs URTD) in the different population groups, we observed that LRTD was more common than URTD in all groups, except among those aged 18–49 y. The difference was especially large among those aged ≥ 75 y, where the incidence was 5,213.5 per 100,000 PY for LRTD, which was more than 14 times higher than 362.0 for URTD. In individuals with comorbidities, the difference was most prominent among those with CHF, where the incidence was 1,222.1 per 100,000 PY for LRTD, which was 16 times higher than 77.4 for URTD (Supplemental Table S5).

The incidence of overall ARI among individuals with comorbidities per age group was also analyzed. In most comorbidities, we observed an increase in the ARI incidence with age except for hematologic disease, advanced liver disease, and chronic renal disease, for which ARI incidence appeared to be comparable across all age groups, and any other CRD, for which ARI incidence decreased with age. The subgroup with the highest overall ARI incidence was patients with COPD aged ≥ 75 y (17,382.8 per 100,000 PY in the 2022/23 season) (Supplemental Table S6).

Prevalence of comorbidities

The prevalence of comorbidities among individuals with overall ARI, RSV, and influenza was analyzed for the 2022/23 season. The most common comorbidities in overall ARI were immunocompromised status, COPD, diabetes, and asthma. The prevalence of comorbidities among RSV cases was similar to, or higher than, that among influenza cases. Hematologic disease and CHF each had a more than two times higher prevalence (factors 2.5 [9.0/3.6] and 2.1 [1.9/0.9], respectively), COPD had a 1.7 times higher prevalence (25.0/14.7), and immunocompromised status had a 1.6 times higher prevalence (31.0/19.3) among RSV cases than among influenza cases (Supplemental Table S7).

Underreporting of RSV hospitalizations

Underreporting of RSV hospitalizations was assessed by comparing ICD-10 codes with microbiological test results for RSV. The sensitivity of the RSV ICD-10 codes was 60% (n = 2,216/3,670), indicating that 40% of the ARI hospital contacts with a microbiological test positive for RSV were not coded as such, i.e., 40% underreporting. The positive predictive value of the RSV ICD-10 codes was 89% (n = 2,216/2,481), suggesting that only 11% of RSV-coded hospitalizations were not confirmed by a positive microbiological test result in MiBa (Supplemental Table S8).

Discussion

We estimated the incidence of ARIs in Danish adults over the past decade with a primary focus on RSV, contextualizing it with influenza estimates. Overall ARI and RSV incidences increased over time, while influenza incidence fluctuated. The RSV and influenza incidences were higher in females, increased with age, and were higher among those with various comorbidities, especially hematologic disease and COPD. Generally, the incidence of RSV was lower than that of influenza, but it was comparable for older adults and those with certain comorbidities.

RSV incidence ranged from 0.4 to 91.6 per 100,000 PY across seasons, which was in the same range as the incidence of 1.9–130 to 0–517 per 100,000 PY among adults with RSV-associated hospitalizations or outpatient visits around the world.⁷ Historically, RSV seasonality in European countries has been regular and predictable.^16,17 However, in this study, in addition to a post-COVID-19 pandemic peak, due to lifting of the pandemic restrictions, we noticed a post-COVID-19 pandemic shift in RSV seasonality from later (January to March) to earlier (October to December) in the season. A similar post-COVID-19 pandemic shift in seasonal pattern was noted in the US and in 11 European countries.^17,18 We require more data from upcoming post-pandemic seasons to determine whether this is a temporary or permanent phenomenon. We found that RSV incidence increased over time, which was in line with other studies.^18,19 This may be attributed to an evolution in RSV testing: RSV testing was limited before 2017, increased with the introduction of point-of-care testing and multiplex assays around 2017/2018, and surged since the start of the COVID-19 pandemic due to both the widespread use of tests that can detect multiple viruses simultaneously and increased awareness and testing.^18,20 We did not have access to the number of RSV tests performed for the entire study period, only to positive RSV test results. However, publicly available data on RSV testing indicates 27,867 tests in the 2020/2021 season, 117,752 in the 2021/2022 season, 161,072 in the 2022/2023 season, 162,827 in the 2023/2024 season, and 146,074 in the 2024/2025 season.²¹ Hence, the rise in RSV incidence reflects improved testing rather than epidemiologic changes. We observed that influenza incidence was generally higher than that of RSV but fluctuated across seasons, with notable peaks in seasons 2017/18 and 2021/22. One factor that may have contributed to the peak in 2017/18 was the dominance of an influenza B strain that was not included in the seasonal vaccine.²² Another factor was the introduction of influenza point-of-care testing outside the regional clinical microbiology departments in 2017.²³ The peak in the 2021/22 season may have been due to the return of seasonal influenza after lifting the COVID-19 pandemic restrictions.

When interpreting our incidence results, it is important to keep in mind that they include only ARIs that had hospital contact or a positive microbiological test. Community cases of ARIs, i.e., ARIs that were not medically attended or that were treated in primary care without microbiological testing, were not included, reflecting an underestimation of the ARI incidence, especially for RSV. Another important point to keep in mind when comparing the incidences of RSV and influenza is that the State Serum Institute, the Danish equivalent of the US Centers for Disease Control and Prevention, showed that the test-positive rate was similar or higher for influenza than for RSV.²⁴ Thus, the higher reported incidence of influenza may be partly explained by differences in testing strategies.

RSV and influenza incidences increased with age and were higher in patients with comorbidities, especially COPD and hematologic disease, in line with previous reports.^19,25–27 This is probably due to older adults and those with comorbidities being at an increased risk of ARIs and more often requiring medical attention when acquiring infections.^28,29 Another possible explanation for the higher incidence in individuals with comorbidities is that, because these patients tend to have close contact with the healthcare system, they may be more likely to be tested for (milder) ARIs than those without comorbidities.³⁰

One of our most notable findings was that RSV and influenza incidences in patients aged ≥ 75 y or with specific comorbidities, such as hematologic disease, COPD, and CHF, were in the same range or slightly higher for RSV. A possible explanation for the difference being less pronounced in older age and in those with comorbidities may be that the influenza vaccine is provided free of charge to high-risk individuals in Denmark,³¹ and has a high coverage (78%) in individuals aged ≥ 65 y.³² That way, influenza incidence is dampened in these groups. In contrast, no RSV vaccines were available in Denmark, not even with out-of-pocket payment, in the seasons we analyzed.¹³ Our results suggest that when prioritizing high-risk groups for future inclusion in a national RSV vaccination program, older adults and those with comorbidities should be considered.

Our data, which show a much higher incidence of LRTD vs URTD among patients aged ≥ 75 y and among those with CHF, also point to a greater severity of ARIs among these patients. These results are in line with previous studies that found that adults with CHF had 4–33 times higher RSV-related hospitalization rates than those without CHF,³³ and that adults aged ≥ 75 y had much higher RSV- and influenza-associated hospitalization rates than younger adults.³⁴ Although RSV and influenza incidences among CHF patients were not higher than in the general population, it seems that when CHF patients had an ARI, it was more severe. This is also important information to consider when developing RSV vaccination programs.

The most common comorbidities in overall ARI were immunocompromised status, COPD, diabetes, and asthma. The prevalences of COPD, diabetes, and asthma were much higher than those reported in the general Danish population.³⁵ No population prevalence data are available for immunocompromised status in Denmark, but it was about four times higher than in adults in Germany and the US.^36,37 The high prevalence of these comorbidities in ARI patients reflects the fact that individuals with these comorbidities are more susceptible to ARI. The prevalence of comorbidities among RSV cases was similar to or higher than that among influenza cases, with the prevalence of hematologic disease and CHF more than two times higher among RSV cases. These findings are in line with previous reports that the prevalence of comorbidities,³⁸ and in particular CHF and COPD,³⁹ was significantly higher among patients with RSV than with influenza.

We found 40% underreporting of RSV ICD-10 codes. This means that studies that only use ICD-10 codes to identify hospitalized patients with RSV are potentially underestimating the RSV incidence. In a study investigating underreporting over three years with a similar methodology, 56% underreporting of RSV was found among hospitalized patients in Denmark.⁴⁰ A similar study in neighboring country Finland found 61% underreporting.⁴¹ The high proportion of underreporting may be explained by low awareness of RSV in adults and a lack of routine testing in hospitals,⁴⁰ a practice that clearly requires improvement. In addition to underreporting, underascertainment may also contribute substantially to the underestimation of the RSV incidence,^42,43 as underascertainment was estimated to lead to a 2.2-fold underestimation of RSV hospitalization,⁴³ and hence an underestimation of RSV’s burden of disease.

The strengths of the present study include its nationwide approach, utilizing various clinical registers in Denmark to assemble a large-scale, population-based cohort that provides critical insights into the epidemiology of RSV-associated ARIs and supports meaningful subgroup analyses. Some potential limitations of this study must be noted. Firstly, due to the absence of ARI surveillance in Denmark in the study period and the tendency for ARIs to cause mild symptoms in healthy adults, the incidences are likely underestimated and skewed toward more severe cases requiring medical care. Secondly, the underestimation of the RSV incidence was also due to a lack of awareness about RSV in patients hospitalized with ARI, resulting in “selective testing” as many such patients not being tested for RSV. Thirdly, the lack of widespread RSV testing during earlier seasons could have introduced a form of selection bias; however, after the introduction of point-of-care testing in later seasons, RSV testing became more common,⁴⁴ which may have contributed to the increase in RSV incidence over time. Fourthly, we did not validate the administrative codes, such as the ICD-10 codes used to identify ARI-specific hospitalizations, which may have affected our data. In a systematic review assessing the performance of ICD-10 codes to identify RSV, influenza, and SARS-CoV-2, it was concluded that using ICD-10 codes to identify these ARIs may lead to underestimation.⁴⁵ Lastly, we did not calculate confidence intervals for the incidence estimates. These analyses were unfortunately not originally planned and could therefore not be added after the study’s finalization. In future studies, we will include these analyses in the analysis plan.

Conclusion

Our study adds to the growing body of evidence indicating that RSV is an important cause of ARIs among adults. The incidence of overall ARI, including RSV and influenza, was higher among older adults and those with certain underlying comorbidities. While influenza incidence was generally higher than that of RSV, incidences were similar for adults aged ≥ 65 y and those with certain comorbidities. Our findings underscore the substantial burden of RSV, which is relevant for public health planning and clinical decision-making, particularly given the recent approval of three highly effective vaccines.

Biography

Maria João Fonseca, graduated in 2009 and completed a PhD in Public Health in 2015. During 2009–2019, she worked as a researcher at the University of Porto, and she lectured on Epidemiology. During 2020, she worked as an epidemiologist at the Portuguese Institute of Oncology. In 2021, she joined IQVIA as an epidemiologist, supporting scientific projects on a wide range of indications. In 2023, she joined GSK’s VEO Europe team, leading RWE studies across Europe, and in 2024, she moved into a global role, still focusing on RSV. She is the first author of several peer-reviewed publications, as well as communications presented in international conferences.

Funding Statement

GlaxoSmithKline funded this study [GlaxoSmithKline study identifier: VEO-000722] and was involved in all stages of study conduct. GlaxoSmithKline also took in charge all costs associated with the development and publication of this manuscript. EY analysts, authorized by Statistics Denmark, conducted all individual-level analyses in a secure environment. GlaxoSmithKline and clinical experts did not access individual-level data and reviewed only aggregated outputs.

Disclosure statement

NVD is employed by GSK. AM, ET, MJF, RR, and SB are employed by GSK and hold financial equities in GSK. MH is employed by Rigshospitalet – University of Copenhagen, which received research grants from AstraZeneca and payment related to support for attending meetings and/or travel from Advance Pharma and Gilead. MH received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AstraZeneca, Bavarian Nordic, GSK, and Leo Pharma. The author also received personal payments for having participated in the Advisory Board at GSK, MSD, AstraZeneca, and Bavarian Nordic. MK and MP are employed by EY-Parthenon, which received consulting fees from GSK; YÇ is employed by the Department of Respiratory Medicine and the Copenhagen General Population Study, Copenhagen University Hospital – Herlev and Gentofte, which received grants and support for attending meetings and/or travel from Sanofi. The author received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, GSK, Chiesi Farmaceutici, and Sanofi. The author also received personal payments for having participated in the Advisory Board at GSK. TP is a contingent worker for GSK. TP received consulting fees from Pathfinder, John Snow Inc, GambleAware, International Centre for Research on Women, and UNAIDS through Impact Epilysis. TP received consulting fees from BioNTech and UCB. The author declares contracts with Impact Epilysis, BioNTech, GSK and UCB. These authors declare no other financial and non-financial relationships or activities.

Data availability statement

For requests for access to anonymized subject level data, please contact corresponding author.

Ethical statement

This study analyzed aggregated, de-identified data; therefore, informed consent and approval from an ethics committee or institutional review board were not required.

Trademark

AREXVY is a trademark owned by or licensed to the GSK group of companies.

ABRYSVO is a trademark of Pfizer.

mRESVIA is a trademark of Moderna.

Supplemental material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21645515.2026.2638638

Abbreviations

ARI

acute respiratory infection

CHF

chronic heart failure

CI

confidence interval

COPD

chronic obstructive pulmonary disease

COVID-19

coronavirus disease 2019

CRD

chronic respiratory disease

ICD-10

International Classification of Diseases, 10th Revision

LRTD

lower respiratory tract disease

MACE

major adverse cardiovascular events

MiBa

Danish Microbiology Database

PY

person-years

RSV

respiratory syncytial virus

SARS-CoV-2

severe acute respiratory syndrome coronavirus 2

URTD

upper respiratory tract disease

US

United States