Diagnostic Accuracy of Severe Acute Respiratory Infection Definitions in Hospitalized Children: A Systematic Review and Meta-Analysis.

Importance: Following the 2009 H1N1 influenza pandemic, the World Health Organization (WHO) established a new case definition for severe acute respiratory infection (SARI) for viral surveillance. Several studies have suggested that SARI case definitions are inaccurate at detecting pediatric disease burden. Understanding the performance of SARI case definitions in children is important for pandemic preparedness. Objectives: To evaluate the diagnostic accuracy of SARI case definitions in detecting microbiologically confirmed viral respiratory tract infections among hospitalized children. Data Sources: The MEDLINE(R), Embase Classic + Embase, Ovid EBM Reviews Cochrane Central Register of Controlled Trials, Elsevier SCOPUS, and the WHO Global Index Medicus databases were searched from inception to March 31, 2025. Study Selection: Study screening was conducted in duplicate by 2 independent reviewers. Any studies that assessed any SARI definition in hospitalized children were included. There were no restrictions by design, time period, or geographical location. Data Extraction and Synthesis: Data extraction using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline was conducted by 1 author using a predefined template and independently validated by a second author. Diagnostic accuracy was extracted as 2 × 2 tables from each study and pooled using a bivariate random-effects model. Quality assessments were conducted using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Main Outcomes and Measures: The primary outcomes were sensitivity and specificity. For each case definition-virus combination with at least 4 included studies, pooled estimates of sensitivity and specificity were calculated. Results: Of 1144 studies identified, 13 were included. Included studies represent surveillance data from 65 inpatient sites across 8 countries, using data from 2007 to 2023. The most common definition was the 2014 WHO SARI (9 studies). Viral pathogens included influenza (10 studies) and respiratory syncytial virus (RSV; 6 studies). Meta-analysis of the WHO 2014 SARI definition yielded a sensitivity of 75.7% (95% CI, 65.0%-83.9%; I2 = 89.2%) and specificity of 30.6% (95% CI, 19.8%-44.0%; I2 = 99.0%) for influenza (7 studies) and sensitivity of 70.6% (95% CI, 56.9%-81.9%; I2 = 98.8%) and specificity of 38.7% (95% CI, 25.7%-53.5%; I2 = 99.5%) for RSV (5 studies). In younger subgroups, sensitivity appeared to decrease while specificity appeared to increase for both influenza and RSV. Conclusions and Relevance: In this systematic review and meta-analysis of 13 studies, the WHO 2014 SARI definition demonstrated reduced sensitivity and increased specificity in younger pediatric cohorts, suggesting that surveillance systems that rely on SARI case definitions may potentially underestimate disease burden in children.