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Journal of Thoracic Disease logoLink to Journal of Thoracic Disease
. 2026 Feb 26;18(2):131. doi: 10.21037/jtd-2025-288

Global, regional, and national burden of upper respiratory infections in adolescents and young adults: an analysis of the Global Burden of Disease Study 2021

Routing Ma 1, Yuxin Huang 2, Qihui Guo 3, Shuyan Wu 4, Guoming Chen 5, Wenhua Jian 6,7,✉, Yijun Chen 6,7,8,✉
PMCID: PMC12972799  PMID: 41816425

Abstract

Background

Upper respiratory infections (URIs) impose a substantial global disease burden; however, the evolving epidemiological landscape, specifically for adolescents and young adults (aged 10–24 years), remains obscured by aggregate analyses. Given that this demographic represents a critical phase for human capital development, understanding the long-term trends of URIs is vital for optimizing resource allocation and intervention strategies. This study aimed to quantify the global, regional, and national burden of URIs in this pivotal group from 1990 to 2021 and project trends to 2035, informing targeted public health policies.

Methods

Data were derived from the Global Burden of Disease (GBD) Study 2021. Annual incidence, mortality, and disability-adjusted life years (DALYs) were analyzed across three age subgroups (10–14, 15–19, and 20–24 years). Temporal trends in age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) were evaluated using estimated annual percentage changes (EAPC). The average annual percent change (AAPC) summarized the overall trend. A Bayesian age-period-cohort (BAPC) model was employed to forecast disease burden through 2035. Analyses were stratified by sex, region, and socio-demographic index (SDI).

Results

From 1990 to 2021, global ASIR declined slightly (EAPC =−0.16%), while ASMR (−1.69%) and ASDR (−0.26%) showed more substantial reductions. The 10–14 years age group consistently had the highest incidence and DALYs burden, with the slowest mortality decline (EAPC =−1.34%), whereas the 20–24 years age group demonstrated the most rapid improvement. Males experienced steeper mortality reductions (−2.25%) than females (−1.11%). Contrasting global improvements, the high-middle SDI region exhibited a significant upward trend in ASIR (EAPC =0.02%), and increases were also observed in the Caribbean and parts of sub-Saharan Africa. Projections indicate a continued decline in rates but a paradoxical rise in absolute case numbers among older adolescents (15–24 years) by 2035.

Conclusions

While the global mortality and DALYs burden of URIs in adolescents and young adults has improved, incidence remains persistently high, particularly in the 10–14 years age group and high-middle SDI regions. The projected rise in case numbers among older cohorts suggests emerging challenges, potentially linked to immunity gaps. Future strategies must prioritize targeted interventions in high-burden demographics and environmental pollution mitigation.

Keywords: Upper respiratory infections (URIs), global disease burden, age-standardized rates, estimated annual percentage changes (EAPC), health disparities

Highlight box.

Key findings

• From 1990 to 2021, global upper respiratory infections (URIs) mortality and disability-adjusted life years declined substantially among individuals aged 10–24 years, largely attributable to healthcare advances and vaccination. Incidence increases in high-middle socio-demographic index regions and parts of Africa and the Caribbean were linked to epidemiological transitions and surveillance improvements. The 10–14 years age group consistently carried the highest burden, reflecting school-based transmission dynamics, while males experienced faster mortality reductions due to targeted interventions. Projections to 2035 suggest a resurgence in cases among the 10–24 years demographic, potentially resulting from immunity debt and vaccination gaps following the coronavirus disease 2019 (COVID-19) pandemic.

What is known and what is new?

• URIs are ubiquitous but are often marginalized in public health agendas or conflated with lower respiratory infections in general “all-age” studies.

• This study provides the first comprehensive Global Burden of Disease 2021 quantification specifically for the 10–24 years demographic, uncovering trends masked by data on infants and older adults, and forecasting the “immunity debt” impact on disease burden up to 2035.

What is the implication, and what should change now?

• The projected resurgence in cases suggests emerging immunity gaps post-COVID-19. Policy must shift towards targeted catch-up vaccination, environmental pollution mitigation in transitional economies, and precision surveillance systems to manage the evolving burden in this strategic population.

Introduction

Upper respiratory infections (URIs) constitute the most prevalent infectious diseases globally, with an estimated 12.8 billion incident cases documented in 2021 (1). Affecting the nasal cavity, pharynx, larynx, and upper airways, these infections typically manifest as cough, sore throat, nasal congestion, and headache (2). While viruses such as influenza, coronaviruses, and respiratory syncytial virus (RSV) are the predominant pathogens, bacterial superinfections frequently exacerbate disease severity (3-5). Despite the ubiquity, URIs are frequently marginalized in public health agendas due to relatively low mortality rates (6,7). However, this neglect underestimates the substantial socioeconomic burden arising from healthcare expenditures, absenteeism, and long-term sequelae (8-11). For example, the substantial economic losses recorded in the United States highlight the financial strain imposed by these infections (12). Crucially, this burden is unevenly distributed and intrinsically linked to socioeconomic factors (13). Therefore, analyzing the URIs burden in relation to the socio-demographic index (SDI) is critical to elucidate how development disparities shape disease outcomes globally.

Adolescents and young adults (aged 10–24 years) represent a pivotal yet vulnerable demographic, accounting for 25.2% of the global population (14). This developmental phase is characterized by profound physiological, social, and neurocognitive transformations, including immune maturation, heightened risk-taking behaviors, and expanding social networks (15-18), which collectively amplify pathogen exposure risks. Although adolescent health is fundamental to current well-being, future adulthood, and the health of the next generation (19), the specific needs of this population remain inadequately addressed. Between 2016 and 2021, dedicated funding for adolescent health comprised merely 2.4% of total global development assistance for health, a figure disproportionately low relative to the demographic’s substantial population share (19).

Despite the strategic significance of this cohort, systematic assessments of the URIs burden in adolescents and young adults remain inadequate. Existing clinical trials disproportionately focus on infants and young children (20,21) or are constrained by limited sample sizes and restricted geographic contexts (22,23), thereby failing to capture the global epidemiological landscape. Similarly, basic research relying on animal models is hindered by species specificity, making it difficult to accurately recapitulate human immune responses and social behaviors (24-26). At the macro level, while recent Global Burden of Disease (GBD) 2021 studies have updated general URIs estimates (1,27), these global analyses primarily utilize an “all-age” approach. This aggregation obscures the distinct epidemiological patterns of the youth demographic due to the masking effect imposed by the high burden in infants and the elderly. Furthermore, previous analyses have often conflated URIs with lower respiratory infections (LRIs), excluded the vital 20–24 years working-age demographic (28), or relied on pre-pandemic data (29).

In response to the need for precise epidemiological characterization of this demographic, this study utilizes the GBD 2021 analytical framework to systematically quantify the global, regional, and national burden of URIs specifically for individuals aged 10–24 years. Incidence, mortality, and disability-adjusted life years (DALYs) were analyzed across the age subgroups of 10–14, 15–19, and 20–24 years, stratified by SDI and geographical regions to underscore systemic inequalities. Building on this historical assessment, future disease trends are also projected through to 2035. By characterizing the temporal and spatial patterns of the URIs burden throughout these key developmental stages, this study aims to provide a robust evidence base to inform targeted national health planning and intervention strategies. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-288/rc).

Methods

GBD source

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Global estimates of URIs burden among adolescents and young adults aged 10–24 years were obtained from the GBD 2021. GBD 2021 provides a comprehensive and annually updated assessment of 369 diseases and 87 risk factors across 204 countries and territories worldwide (30,31).

In this study, URIs-related incidence, mortality, and DALYs for individuals aged 10–24 years from 1990 to 2021 were extracted from the GBD 2021 database. Subgroup analyses were conducted by sex, age group, region, and country to evaluate geographic and demographic variations. URIs are clearly defined within the International Classification of Diseases (ICD). This standardized coding ensures cross-country comparability of case definitions. To more accurately describe the age-specific distribution of URIs in adolescents and young adults, the 10–24 years population was divided into three consecutive age groups: 10–14, 15–19, and 20–24 years. This categorization reflects key developmental transitions from early adolescence through late adolescence to young adulthood, allowing for a clearer depiction of how the disease burden evolves across these critical periods. Furthermore, analyses were stratified by sex to examine potential differences between males and females, thereby providing a more comprehensive understanding of demographic variations in URIs burden.

All data were retrieved through the Global Health Data Exchange query tool maintained by the Institute for Health Metrics and Evaluation. This platform provides access to annual case counts and age-standardized indicators, including age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR), disaggregated by year, sex, age, region, and country. The GBD estimation process incorporates diverse data sources, including vital registration systems, hospital admission records, household surveys, verbal autopsy studies, disease registries, and published scientific literature. In regions or time periods with incomplete surveillance—such as low-SDI countries in the early 1990s—data sparsity is addressed through standardized modeling frameworks. Incidence and prevalence estimates are generated using DisMod-MR 2.1, which enforces internal epidemiological consistency across parameters, while mortality estimates rely on the Cause of Death Ensemble Model. Spatiotemporal Gaussian process regression is employed to improve estimates by borrowing information across adjacent years and locations, thereby compensating for gaps in population monitoring systems. These procedures ensure that estimates remain robust, comparable, and methodologically consistent across countries and over time. Detailed modeling procedures, parameter specifications, and computational methods are available in the GBD methodological articles published in The Lancet (32). Global incidence, prevalence, years lived with disability (YLDs), DALYs, and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the GBD Study 2021 By utilizing URIs estimates from GBD 2021, this study was able to characterize long-term trends and patterns in the global disease burden of URIs among adolescents and young adults, offering important insights into the epidemiology of these conditions across different demographic and geographic contexts.

Statistical analysis

All statistical analyses were performed using R (version 4.4.2), coupled with the JD_GBDR (V2.33, Jingding Medical Technology Co., Ltd., Xiamen, China), which supports standardized processing of GBD-derived indicators. ASIR, ASMR, and ASDR were summarized with corresponding 95% uncertainty intervals (UIs), calculated from the 2.5th and 97.5th percentiles of 1,000 posterior draws (30).

To evaluate temporal patterns, the estimated annual percentage changes (EAPC) and their 95% confidence interval (CI) were computed to quantify long-term trends in age-standardized rates (33). In addition, age-period-cohort indicators, including the annual percent change (APC) and the average annual percent change (AAPC), were calculated to further characterize period and cohort effects. For burden forecasting, the Bayesian age-period-cohort (BAPC) model was applied to integrate historical observations with structured age, period, and cohort components, enabling probabilistic projections of future trends in the burden of URIs. Statistical significance was defined as a two-sided P value <0.05. Detailed computational procedures are provided in Appendix 1.

Results

Global burden and trend of URIs in adolescents and young adults

From 1990 to 2021, global analysis of 10 to 24 years old revealed declining trends in age-standardized incidence, mortality, and DALYs rates. The steepest reduction was in the ASMR (EAPC =−1.69%), followed by the ASDR (EAPC =−0.26%) and the ASIR (EAPC =−0.16%) (Table 1).

Table 1. ASIR, ASMR, ASDR, and EAPC of URIs, from 1990 to 2021, by sex, SDI levels, and GBD regions.

Group ASIR (per 100,000 population) ASMR (per 100,000 population) ASDR (per 100,000 population) EAPC of incidence rate [1990–2021], % EAPC of mortality rate
[1990–2021], %		 EAPC of DALYs rate
[1990–2021], %
1990 2021 1990 2021 1990 2021
Global 170,387.56 (119,570.31, 231,541.42) 163,388.21 (114,433.40, 222,730.77) 0.08 (0.02, 0.14) 0.05 (0.01, 0.11) 64.74 (36.88, 103.31) 60.11 (33.62, 96.88) −0.16 (−0.17, −0.15) −1.69 (−1.88, −1.51) −0.26 (−0.27, −0.25)
Sex
   Female 173,058.81 (121,245.08, 235,223.82) 166,029.97 (116,342.92, 225,876.53) 0.07 (0.01, 0.15) 0.05 (0.01, 0.14) 64.94 (36.34, 103.40) 61.04 (33.93, 98.48) −0.15 (−0.16, −0.14) −1.11 (−1.24, −0.98) −0.21 (−0.22, −0.20)
   Male 167,790.21 (117,780.63, 228,139.72) 160,870.14 (112,548.24, 219,696.55) 0.08 (0.02, 0.15) 0.04 (0.01, 0.10) 64.55 (36.81, 102.42) 59.23 (32.81, 96.22) −0.16 (−0.17, −0.15) −2.25 (−2.48, −2.01) −0.30 (−0.32, −0.29)
Age (years)
   10–14 180,639.24 (126,030.90, 247,689.66) 171,067.25 (118,997.44, 235,587.82) 0.09 (0.02, 0.18) 0.06 (0.01, 0.14) 70.50 (40.00, 113.35) 64.62 (35.92, 104.77) −0.16 (−0.18, −0.15) −1.34 (−1.50, −1.19) −0.26 (−0.27, −0.25)
   15–19 166,940.67 (115,883.42, 224,656.04) 160,574.24 (111,176.95, 216,450.95) 0.06 (0.02, 0.11) 0.04 (0.01, 0.09) 62.23 (35.47, 98.40) 58.22 (32.31, 92.86) −0.15 (−0.17, −0.14) −1.75 (−1.99, −1.52) −0.24 (−0.26, −0.22)
   20–24 162,231.43 (116,039.73, 220,240.99) 157,525.42 (112,631.88, 214,581.15) 0.07 (0.02, 0.13) 0.04 (0.01, 0.09) 60.79 (34.81, 96.94) 56.93 (32.35, 92.06) −0.15 (−0.18, −0.12) −2.19 (−2.43, −1.95) −0.27 (−0.30, −0.24)
SDI
   High SDI 237,109.66 (166,734.98, 319,571.55) 225,027.44 (158,378.23, 302,982.57) 0.02 (0.02, 0.02) 0.00 (0.00, 0.00) 83.70 (45.78, 135.47) 78.17 (42.27, 128.23) −0.38 (−0.46, −0.30) −5.44 (−5.95, −4.93) −0.42 (−0.49, −0.34)
   High-middle SDI 162,144.62 (113,487.83, 220,886.93) 163,849.11 (114,815.91, 222,967.25) 0.06 (0.02, 0.09) 0.01 (0.01, 0.01) 61.16 (34.72, 97.81) 57.60 (31.11, 94.30) 0.02 (0.01, 0.04) −7.88 (−8.31, −7.44) −0.22 (−0.26, −0.18)
   Low SDI 148,743.08 (103,259.20, 204,230.61) 147,426.97 (102,093.77, 202,807.21) 0.22 (0.01, 0.62) 0.16 (0.01, 0.43) 67.58 (33.11, 110.32) 62.67 (31.82, 100.28) −0.01 (−0.03, 0.02) −1.22 (−1.33, −1.11) −0.26 (−0.29, −0.23)
   Low-middle SDI 159,011.42 (111,181.72, 216,507.82) 153,551.34 (107,011.51, 209,348.31) 0.05 (0.01, 0.12) 0.03 (0.01, 0.07) 58.80 (32.80, 94.91) 55.75 (30.65, 90.17) −0.07 (−0.10, −0.04) −1.32 (−1.44, −1.19) −0.13 (−0.16, −0.10)
   Middle SDI 164,855.41 (115,267.65, 224,154.51) 163,092.04 (114,067.49, 222,462.67) 0.08 (0.02, 0.12) 0.01 (0.01, 0.02) 62.97 (35.76, 100.29) 57.69 (31.34, 94.53) −0.04 (−0.05, −0.03) −6.53 (−6.77, −6.28) −0.29 (−0.32, −0.25)
GBD regions
   Andean Latin America 191,788.22 (133,819.24, 260,902.08) 189,908.49 (132,843.56, 259,635.81) 0.04 (0.02, 0.09) 0.01 (0.01, 0.01) 69.77 (37.87, 112.80) 66.78 (35.56, 110.96) −0.05 (−0.06, −0.03) −5.37 (−5.59, −5.16) −0.16 (−0.18, −0.14)
   Australasia 228,908.53 (159,125.04, 310,887.65) 227,081.54 (158,431.83, 310,899.25) 0.02 (0.01, 0.02) 0.01 (0.00, 0.01) 80.39 (42.85, 132.26) 78.94 (42.37, 130.69) −0.03 (−0.04, −0.03) −3.53 (−4.65, −2.41) −0.06 (−0.07, −0.05)
   Caribbean 175,412.37 (123,097.43, 237,386.97) 176,276.31 (123,904.02, 239,747.83) 0.03 (0.02, 0.07) 0.02 (0.01, 0.04) 63.31 (34.83, 103.93) 62.49 (33.88, 101.96) 0.01 (0.00, 0.01) −2.24 (−2.63, −1.85) −0.05 (−0.06, −0.04)
   Central Asia 109,889.13 (76,518.58, 151,095.02) 106,364.19 (74,309.28, 145,586.98) 0.06 (0.04, 0.08) 0.03 (0.02, 0.04) 42.22 (24.56, 66.59) 39.12 (21.79, 63.13) −0.12 (−0.12, −0.11) −2.36 (−2.73, −2.00) −0.30 (−0.33, −0.27)
   Central Europe 143,573.50 (99,960.26, 195,615.91) 143,372.03 (100,295.27, 195,332.32) 0.01 (0.01, 0.02) 0.00 (0.00, 0.00) 50.81 (27.80, 83.41) 49.90 (26.90, 81.54) −0.02 (−0.02, −0.01) −5.81 (−6.23, −5.38) −0.07 (−0.07, −0.06)
   Central Latin America 193,266.77 (135,259.86, 262,479.35) 190,169.20 (133,048.90, 259,507.97) 0.08 (0.07, 0.09) 0.01 (0.01, 0.01) 73.36 (42.31, 117.03) 67.25 (36.52, 109.80) −0.06 (−0.07, −0.05) −6.74 (−6.92, −6.56) −0.28 (−0.31, −0.25)
   Central Sub-Saharan Africa 165,989.04 (115,486.21, 225,020.00) 161,829.73 (112,935.04, 222,007.48) 0.23 (0.01, 0.75) 0.17 (0.01, 0.64) 74.04 (37.22, 124.57) 68.07 (35.00, 114.28) −0.08 (−0.08, −0.07) −0.91 (−1.09, −0.73) −0.24 (−0.28, −0.20)
   East Asia 133,861.48 (93,236.47, 183,373.74) 132,588.68 (92,356.22, 182,200.14) 0.12 (0.02, 0.19) 0.01 (0.00, 0.02) 55.62 (32.64, 86.26) 46.97 (25.41, 76.70) −0.01 (−0.02, 0.00) −10.10 (−10.62, −9.58) −0.57 (−0.64, −0.51)
   Eastern Europe 191,838.97 (135,375.77, 261,389.34) 191,571.24 (134,845.18, 260,209.37) 0.07 (0.06, 0.07) 0.02 (0.01, 0.02) 71.32 (40.59, 115.39) 67.69 (36.78, 110.90) −0.01 (−0.01, 0.00) −5.06 (−5.36, −4.77) −0.20 (−0.22, −0.18)
   Eastern Sub-Saharan Africa 162,712.38 (113,174.33, 224,530.51) 163,318.58 (113,897.15, 225,330.38) 0.34 (0.01, 0.91) 0.24 (0.01, 0.68) 81.29 (37.05, 134.79) 73.69 (35.57, 121.99) 0.01 (0.00, 0.03) −1.41 (−1.52, −1.30) −0.37 (−0.41, −0.34)
   High-income Asia Pacific 238,965.96 (166,856.26, 322,350.90) 238,538.33 (166,761.34, 323,016.73) 0.02 (0.01, 0.04) 0.00 (0.00, 0.00) 85.17 (46.76, 139.46) 83.58 (45.31, 138.72) −0.03 (−0.05, −0.02) −10.65 (−11.20, −10.10) −0.08 (−0.10, −0.07)
   High-income North America 329,291.53 (230,461.01, 441,578.53) 281,145.29 (197,619.07, 380,359.52) 0.02 (0.02, 0.02) 0.01 (0.01, 0.01) 115.20 (62.74, 187.73) 97.15 (51.82, 158.62) −0.96 (−1.13, −0.80) −3.34 (−3.86, −2.83) −0.98 (−1.15, −0.82)
   North Africa and Middle East 159,529.15 (111,464.65, 216,943.02) 152,926.63 (106,983.46, 208,832.44) 0.01 (0.00, 0.03) 0.01 (0.00, 0.01) 56.30 (30.40, 92.39) 53.49 (28.91, 87.76) −0.14 (−0.15, −0.14) −1.97 (−2.26, −1.68) −0.16 (−0.17, −0.15)
   Oceania 203,367.05 (141,845.39, 273,430.64) 202,452.24 (140,480.97, 275,813.72) 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 70.71 (37.94, 118.57) 70.57 (36.92, 117.42) −0.02 (−0.03, −0.01) −1.78 (−1.92, −1.64) −0.01 (−0.02, 0.00)
   South Asia 144,751.75 (100,713.69, 197,484.89) 141,296.37 (98,326.89, 192,648.83) 0.03 (0.00, 0.07) 0.01 (0.00, 0.03) 52.13 (28.54, 84.54) 49.93 (27.17, 81.28) −0.02 (−0.06, 0.01) −2.42 (−2.75, −2.08) −0.09 (−0.13, −0.05)
   Southeast Asia 201,706.69 (140,504.92, 273,088.59) 186,095.72 (128,313.84, 256,155.68) 0.03 (0.01, 0.05) 0.01 (0.01, 0.02) 72.22 (39.30, 117.84) 65.88 (35.52, 109.12) −0.31 (−0.35, −0.27) −3.48 (−3.54, −3.42) −0.34 (−0.38, −0.30)
   Southern Latin America 226,429.03 (157,295.94, 307,879.86) 226,104.39 (156,976.89, 307,714.44) 0.01 (0.01, 0.02) 0.00 (0.00, 0.00) 79.42 (43.25, 131.94) 78.69 (41.96, 130.57) −0.02 (−0.03, −0.01) −4.78 (−5.33, −4.23) −0.05 (−0.06, −0.04)
   Southern Sub-Saharan Africa 224,211.46 (155,029.62, 306,230.31) 210,911.57 (145,421.69, 288,954.51) 0.15 (0.07, 0.29) 0.12 (0.06, 0.20) 88.63 (51.58, 139.71) 81.55 (46.38, 130.71) −0.20 (−0.25, −0.16) −0.68 (−1.08, −0.27) −0.25 (−0.33, −0.17)
   Tropical Latin America 245,489.90 (170,130.66, 332,488.09) 231,253.83 (159,031.19, 314,477.70) 0.03 (0.03, 0.03) 0.02 (0.02, 0.02) 87.51 (47.81, 143.80) 81.95 (44.29, 135.35) −0.11 (−0.16, −0.06) −0.85 (−1.39, −0.31) −0.12 (−0.18, −0.07)
   Western Europe 192,741.43 (134,654.59, 261,132.66) 191,677.82 (133,606.96, 260,513.16) 0.02 (0.02, 0.02) 0.00 (0.00, 0.00) 68.03 (36.69, 111.64) 66.73 (35.97, 110.89) −0.03 (−0.04, −0.01) −5.21 (−5.37, −5.06) −0.07 (−0.08, −0.06)
   Western Sub-Saharan Africa 148,378.11 (103,086.81, 204,388.40) 145,515.53 (100,551.71, 200,721.63) 0.25 (0.01, 0.82) 0.16 (0.01, 0.47) 69.56 (33.19, 119.63) 62.27 (32.01, 101.75) 0.00 (−0.06, 0.07) −1.39 (−1.48, −1.29) −0.31 (−0.35, −0.27)
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Data are presented as value (95% CI). ASDR, age-standardized DALYs rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; CI, confidence interval; DALYs, disability-adjusted life years; EAPC, estimated annual percentage changes; GBD, Global Burden of Disease; SDI, socio-demographic index; URIs, upper respiratory infections.

Female ASIR has consistently been higher than that of males and remained elevated in 2021, with 166,029.972 per 100,000 (95% UI: 116,342.918, 225,876.529). However, subsequent trends favored males, who experienced a faster decline in both mortality and disability burden: the ASMR decreased at an EAPC of −2.25% (95% CI: −2.48%, −2.01%) in males and −1.11% (95% CI: −1.24%, −0.98%) in females, while the ASDR declined at an EAPC of −0.30% (95% CI: −0.32%, −0.29%) in males compared to −0.21% (95% CI: −0.22%, −0.20%) in females (Figure 1, Figure S1 and Tables S1-S3).

Figure 1.

Figure 1

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Trends in global incidence numbers by gender and age group, 1990–2021 (A), trends in global deaths numbers by gender and age group, 1990–2021 (B), and trends in global DALYs numbers by gender and age group, 1990–2021 (C). DALYs, disability-adjusted life years; UI, uncertainty interval.

Among age subgroups, the 10–14 years group consistently had the highest ASIR through 2021, at 171,067.25 per 100,000 (95% UI: 118,997.44, 235,587.82), and the highest DALYs burden, with a rate of 64.62 (95% UI: 35.92, 104.77) in 2021—7.69 points higher than the 20–24 years group. However, it experienced the slowest decline in ASMR (EAPC =−1.34%; 95% CI: −1.50%, −1.19%). In contrast, the 20–24 years group showed the most rapid improvement, with the fastest ASMR decline (EAPC =−2.19%; 95% CI: −2.43% to −1.95%) and the largest ASDR reduction (EAPC =−0.27%; 95% CI: −0.30% to −0.24%) (Figure 2, Figure S1 and Tables S4-S6).

Figure 2.

Figure 2

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Trends in URIs incidence rates among 10–24 years individuals (three age groups: 10–14, 15–19, and 20–24 years), globally and across five SDI regions, 1990–2021 (A); mortality rates (B); DALYs rates (C). DALYs, disability-adjusted life years; SDI, socio-demographic index; URIs, upper respiratory infections.

URIs in adolescents and young adults among different SDI regions

ASIR declined across most SDI regions, with only the high-middle SDI region seeing an increase—its AAPC reaches 0.03. The high SDI region, by contrast, had the highest baseline ASIR in 1990, reaching 237,109.66 per 100,000 (95% UI: 166,734.98, 319,571.55) (Table 1) and recorded the steepest initial decline, with an AAPC of −0.198 and a 95% CI of −0.250 to −0.1462 (Table S7).

According to the APC data, the resurgence of URIs incidence globally around 2020 had already emerged in these two regions as early as the 2010s (Figure 3), while the overall mortality rate and DALYs rate showed a decreasing trend (Figures S2,S3). The high-middle SDI region led this uptick: it exhibited a steady upward trend in URIs incidence, with an APC of 0.17% (95% CI: 0.16%, 0.18%) during 2008–2016, and the increasing trend persisted, albeit at a slower pace, in 2016–2021, with an APC of 0.02% (95% CI: 0.00%, 0.04%). Even the high SDI region, which exhibited an overall declining trend in the early periods, saw a clear rebound from 2014 onwards, with its incidence increasing by an APC of 0.29% (95% CI: 0.20%, 0.38%) through 2021 (Table 2).

Figure 3.

Figure 3

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APCs in incidence among individuals aged 10–24 years in global and five different SDI regions, 1990–2021. APCs, annual percent changes; SDI, socio-demographic index.

Table 2. APCs and 95% CIs of URIs incidence among individuals aged 10–24 years in different SDI regions.

Causes Year APC (95% CI), %
Global 1990–1993 0.04 (−0.02 to 0.10)
1994–2001 −0.10 (−0.12 to −0.08)
2002–2010 −0.21 (−0.22 to −0.19)
2011–2021 −0.17 (−0.18 to −0.16)
High SDI 1990–2000 0.32 (0.27 to 0.36)
2001–2004 −0.73 (−0.95 to −0.51)
2005–2009 −1.11 (−1.26 to −0.96)
2010–2014 −0.57 (−0.73 to −0.42)
2015–2021 0.29 (0.20 to 0.38)
High-middle SDI 1990–1997 0.07 (0.06 to 0.07)
1998–2005 −0.09 (−0.10 to −0.09)
2006–2008 −0.06 (−0.09 to −0.02)
2009–2016 0.17 (0.16 to 0.18)
2017–2021 0.02 (0.00 to 0.04)
Middle SDI 1990–1993 0.11 (0.08 to 0.13)
1994–1995 −0.01 (−0.08 to 0.06)
1996–2003 −0.15 (−0.15 to −0.14)
2004–2006 −0.05 (−0.09 to −0.02)
2007–2015 0.06 (0.06 to 0.07)
2016–2021 −0.10 (−0.11 to −0.09)
Low-middle SDI 1990–2000 −0.12 (−0.15 to −0.10)
2001–2009 0.12 (0.09 to 0.15)
2010–2018 −0.26 (−0.29 to −0.23)
2019–2021 −0.56 (−0.74 to −0.38)
Low SDI 1990–1995 −0.06 (−0.09 to −0.03)
1996–2003 0.14 (0.12 to 0.16)
2004–2009 0.07 (0.04 to 0.10)
2010–2014 −0.29 (−0.33 to −0.26)
2015–2021 −0.12 (−0.14 to −0.09)
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APCs, annual percentage changes; CI, confidence interval; SDI, socio-demographic index; URIs, upper respiratory infections.

URIs in adolescents and young adults among different regions and nations

Between 1990 and 2021, substantial disparities in disease burden were observed across regions. High-income North America reported the highest baseline ASIR in 1990 at 329,291.53 per 100,000 (95% UI: 230,461.01, 441,578.53), which declined to 281,145.29 per 100,000 in 2021 (95% UI: 197,619.07, 380,359.52), with an EAPC of −0.96% (95% CI: −1.13% to −0.80%). This region also had the highest 1990 ASDR at 83.70 per 100,000 (95% UI: 45.78, 135.47), which decreased to 78.17 per 100,000 in 2021 (95% UI: 42.27, 128.23; EAPC =−0.42%; 95% CI: −0.49%, −0.34%). Within this region, the United States had the highest 1990 ASIR at 331,209.48 per 100,000 (95% UI: 231,993.44, 444,062.55) and the fastest incidence decline (EAPC =−1.06%; 95% CI: −1.25%, −0.88%), while Canada maintained the highest global ASDR, measuring 108.84 per 100,000 in 1990 and 107.66 per 100,000 in 2021. Greenland, another high-incidence region, had the highest ASIR in 2021 at 311,789.41 per 100,000 (95% UI: 215,564.02, 422,714.05), showing a slight rise from 311,522.59 per 100,000 in 1990 (95% UI: 217,639.36, 422,312.82) (Table 1 and table available at https://cdn.amegroups.cn/static/public/jtd-2025-288-1.docx).

In contrast to the general declining trend, three regions showed slight increases: the Caribbean (EAPC =0.006%; 95% CI: −0.001%, 0.012%), Eastern sub-Saharan Africa (EAPC =0.012%; 95% CI: −0.003%, 0.028%), and Western sub-Saharan Africa (EAPC =0.004%; 95% CI: −0.060%, 0.069%). Eastern sub-Saharan Africa carried the highest ASMR in 1990 at 0.34 per 100,000 (95% UI: 0.01, 0.91), declining to 0.25 (95% UI: 0.01, 0.68) by 2021—five times the 2021 global average of 0.05 per 100,000—with an EAPC of −1.05% (95% CI: −1.21%, −0.89%). Regarding overall health loss, High-income North America had the highest ASDR in 1990 at 83.70 per 100,000 (95% UI: 45.78, 135.47), which fell to 78.17 (95% UI: 42.27, 128.23) in 2021, corresponding to an EAPC of −0.42% (95% CI: −0.49%, −0.34%) (Table 1).

In contrast, the Republic of Tajikistan consistently held the lowest global ASIR, at 86,207.04 per 100,000 in 1990 (95% UI: 58,986.50, 119,462.30) and 86,355.88 per 100,000 in 2021 (95% UI: 59,493.41, 119,903.86). Its ASDR was also the lowest globally, measuring 37.28 per 100,000 in 1990 (95% UI: 20.68, 63.75) and 34.12 per 100,000 in 2021 (95% UI: 19.15, 54.79), remaining stable at low levels (Figure 4).

Figure 4.

Figure 4

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Among 204 countries and territories, the incidence rates (A), mortality rates (B), DALY rates (C) of URIs in 1990; the incidence rates (D), mortality rates (E), DALY rates (F) of URIs in 2021; and the EAPC of incidence rates (G), EAPC of mortality rates (H), EAPC of DALY rates (I) of URIs from 1990 to 2021. DALY, disability-adjusted life year; EAPC, estimated annual percentage changes; URIs, upper respiratory infections.

The Sultanate of Oman had the highest 1990 ASDR at 137.65 per 100,000 (95% UI: 56.99, 302.53) and the highest 1990 ASMR at 1.20 per 100,000 (95% UI: 0.22, 3.46), but achieved the steepest ASDR decline (EAPC =−1.28%; 95% CI: −1.56%, −1.00%). Meanwhile, Taiwan (province of China) recorded the most dramatic mortality decline, with an EAPC of ASMR of −13.02% (95% CI: −13.87%, −12.16%) (Figure 4).

Prediction of global burden and trend of URIs

The global ASIR, ASMR, and ASDR of URIs among the age group of 10–24 years exhibited an overall decline from 1990 to 2035 (Figure 5). This downward trajectory is projected to persist into the future: from 163,388.21 per 100,000 (95% CI: 114,433.40, 222,730.77) in 2021 to a projected 158,892.17 per 100,000 (95% CI: 134,012.80, 183,771.54) in 2035 (Figure 5A and Table S8). Analysis of case numbers reveals divergent trends across specific age subgroups during the 2020–2035 projection window. For the 10–14 years group, a transient increase occurs, with cases rising from 1.12 billion in 2020 to 1.14 billion in 2021, before declining to a projected 1.11 billion in 2035—a net decrease of over 32.92 million cases from 2021 to 2035. Moving to the 15–19 years group, a substantial increase is projected, with cases rising from 1.00 billion in 2021 to 1.05 billion in 2035, an increase of more than 45.87 million. Finally, for those aged 20–24 years, the forecast shows steady growth from 940.68 million cases in 2021 to 1.017 billion in 2035, representing an increase of over 76.47 million cases (Figure 5B and Table S9).

Figure 5.

Figure 5

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BAPC-predicted URIs metrics among individuals aged 10–24 years globally, 1990–2030: global ASIR per 100,000 (A), 10–14 years incidence cases (B), ASMR per 100,000 by age group (C), death cases by age group (D), ASDR per 100,000 by age group (E), and DALY cases by age group (F). Agestd., age-standardized; ASDR, age-standardized DALYs rate; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; BAPC, Bayesian age-period-cohort; DALYs, disability-adjusted life years; URIs, upper respiratory infections.

Discussion

By focusing exclusively on the 10–24 years age demographic, this study addresses the lack of age-specific granularity in previous general population assessments. Isolating this cohort reveals epidemiological trends previously masked by the dominant “U-shaped” burden curves of infants and the elderly (1,27), highlighting specific vulnerabilities associated with immune maturation and behavioral shifts as adolescents assume broader societal roles (34,35). Unlike clinical trials or animal models, which are frequently limited by small sample sizes (22,23), selection bias (20,21), or lack of species specificity (24-26), the GBD macro-epidemiological framework captures real-world exposure patterns across diverse geographic regions. Crucially, strictly differentiating URIs from LRIs removes the mortality-driven statistical bias inherent to LRIs data. This approach isolates the substantial morbidity and productivity losses that characterize the URI burden (28). Furthermore, stratification by SDI exposes systemic inequities, contrasting the economic burden of screening in high-resource settings with the structural healthcare deficits in low-SDI regions that often obscure the true disease prevalence (36-38). Including the 20–24 years age group emphasizes human capital losses within the early-stage workforce, while the utilization of GBD 2021 data incorporates the ecological impact of the coronavirus disease 2019 (COVID-19) pandemic and non-pharmaceutical interventions (NPIs), providing insights into respiratory pathogen dynamics that pre-2020 analyses could not offer (29).

This global analysis reveals sustained declines in ASIR, ASMR, and DALYs rates for URIs among the 10–24 years age group from 1990 to 2021, with the most pronounced reduction occurring in ASMR. However, divergent regional patterns emerged: while global metrics improved, ASIR exhibited slight increases in Eastern and Western sub-Saharan Africa and the Caribbean, and High-middle SDI regions observed a notable upward trend. Regarding sex disparities, males exhibited steeper declines in ASMR and DALYs rates compared to females. Age-stratified analysis indicates that the group aged 10–14 years consistently bore the heaviest disease burden. Future projections indicate an overall declining trend in global URIs incidence but predict a paradoxical rise in disease burden among the older cohorts (15–19 and 20–24 years).

The substantial decline in ASMR likely reflects synergistic public health advancements, primarily driven by the widespread implementation of vaccines, such as pneumococcal conjugate vaccines (PCVs) and Haemophilus influenzae type b (Hib) vaccines. While these pathogens are often associated with LRIs, vaccination effectively prevents primary URIs episodes from progressing to severe downstream complications like pneumonia, thereby curbing URIs-related mortality (39-41). Concurrently, enhanced healthcare accessibility has facilitated the timely treatment of secondary bacterial superinfections, which likely mitigated severe outcomes associated with viral URIs, further contributing to the observed mortality reduction (42,43).

While ASIRs generally declined across most SDI regions, high-middle SDI regions showed a notable upward trend. This pattern highlights the complex interplay between socioeconomic transition, environmental exposures, and healthcare capacity. High SDI regions consistently exhibited the highest baseline ASIRs, likely attributable to advanced surveillance systems where heightened detection capabilities inflate reported incidence relative to lower-resource settings (28). Conversely, the paradoxical increase in high-middle SDI regions indicates escalating environmental risks accompanying rapid industrialization. Rising gross domestic product (GDP) per capita and energy consumption contribute to elevated ambient air pollution, particularly fine particulate matter with diameters equal to or smaller than 2.5 µm (PM2.5) levels (44). Rapid urbanization exacerbates this burden, as higher densities of road junctions and transport hubs correlate positively with PM2.5 concentrations (45). Crucially, ambient particulate matter is established as a leading risk factor for URIs (1). Adolescents in these transitional economies face disproportionate exposure risks due to daily commuting and activities in urban environments where crowding and pollution synergistically elevate susceptibility (46-50).

Contrary to the global decline, the slight increases in ASIR within the Caribbean and sub-Saharan Africa likely reflect a “surveillance artifact”, which represents an outcome of improved case detection rather than a genuine epidemiological surge. Historically, these regions suffered from fragmented monitoring systems and limited health-seeking behaviors, resulting in systematic underreporting and misclassification (51-54). The recent statistical rise primarily stems from the progressive rectification of these data deficits. Frameworks like Universal Health Coverage (UHC) and Global Alliance for Vaccines and Immunization (GAVI) have increased primary care utilization (55-57), while regional capacity-building initiatives (e.g., SARInet) have strengthened pathogen reporting systems (58,59). Future strategies must therefore evolve from basic detection to precision validation, employing multi-sectoral platforms and artificial intelligence (AI)-driven models to distinguish between surveillance improvements and actual disease outbreaks (51,60).

The more pronounced decline in mortality among males likely reflects the mitigation of this group’s inherently higher biological vulnerability. Evidence indicates that males are more susceptible to respiratory infections (61,62) due to immunological dimorphism, such as decreased X-linked TLR7 expression and testosterone-mediated immunosuppression (63-65). Such immunological differences predispose males to higher viral loads and excessive innate immune responses (e.g., “cytokine storms”) (66-68). Consequently, public health interventions have yielded a disproportionate benefit for males: by reducing external risks through vaccination and tobacco control, interventions effectively protect the demographic most prone to severe outcomes. Since males historically exhibit higher smoking prevalence and weaker adaptive immune responses (69-72), widespread vaccination (73,74) acts as a critical equalizer, narrowing the gender gap in mortality.

The 10–14 years age group consistently bore the highest burden across all GBD regions, a pattern driven by specific transmission dynamics and high-density environments. Adolescents in this cohort experience prolonged exposure in congregate settings like schools, where close contact and inadequate ventilation heighten pathogen transmission (48,75). Crucially, evidence indicates that pathogens persist in both aerosols and on surfaces within these facilities, supporting high routine detection rates among students (76,77). Biologically, school-aged children exhibit elevated viral shedding efficiency, often serving as primary vectors introducing viruses into households (78). Furthermore, high viral loads resulting from frequent reinfections intensify community transmission (79), aligning with the seasonal clustering of outbreaks often observed in educational institutions (80,81).

The projections indicate a shifting epidemiological landscape. While overall incidence may decline, the rising burden in older adolescents (15–24 years) is concerning and likely linked to the “immunity debt” created by the COVID-19 pandemic. These cohorts experienced critical disruptions in routine immunization (82,83) and prolonged low microbial exposure due to NPIs (84,85), compromising innate immune training and natural protection against pathogens like RSV and influenza (86-88). The relaxation of NPIs has already triggered delayed resurgences of these pathogens. To mitigate this, multilayered strategies are imperative: prioritizing catch-up vaccination campaigns for core pathogens (85,89), deploying adaptive hygiene measures for non-vaccine-preventable viruses, and leveraging COVID-19 infrastructure to establish quantitative surveillance systems (e.g., Pathogen Population Density scoring) (90). These measures are vital to manage the rebound susceptibility in this strategic population.

Methodologically, these findings leverage the GBD 2021 framework’s strengths in standardizing cross-country comparisons through disability weights and Bayesian modeling. However, limitations persist. The underreporting of mild URIs cases in low-resource settings likely leads to an underestimation of the true burden. Furthermore, the model’s reliance on healthcare access covariates may oversimplify the complex interactions between environmental stressors and socioeconomic disparities. Additionally, the lack of granular data in this study on specific behavioral risk factors within GBD restricts the ability to perform causal inference for specific age groups. Future research warrants primary data validation in high-burden regions to refine these macro-level estimates.

Conclusions

From 1990 to 2021, the global burden of URIs among adolescents and young adults generally declined, yet significant regional disparities and a persistent high burden in the 10–14 years age group remain. Notably, sex-specific trends reveal faster mortality reductions in males. Given the projected resurgence in the 15–24 years age cohort, prioritizing targeted vaccination and strengthening surveillance systems are imperative to address these evolving epidemiological challenges.

Supplementary

The article’s supplementary files as

jtd-18-02-131-rc.pdf (658.7KB, pdf)
DOI: 10.21037/jtd-2025-288
jtd-18-02-131-coif.pdf (3.1MB, pdf)
DOI: 10.21037/jtd-2025-288
jtd-18-02-131-supplementary.pdf (1.7MB, pdf)
DOI: 10.21037/jtd-2025-288

Acknowledgments

None.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Footnotes

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-288/rc

Funding: This work was supported by the Major Project of Guangzhou National Laboratory (No. GZNL2024A01002) and the Guangzhou Health Science and Technology project (No. 20231A011078).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-288/coif). The authors have no conflicts of interest to declare.

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