Purpose: Acute respiratory infections (ARI) are common reasons for medical visits in children. Current surveillance systems are focused on reported cases of ARI or influenza-like illness (ILI) at the population level, but universal measures for individual-level disease severity have been lacking. Meanwhile, regulatory authorities are asking for the development of standardized clinical outcome measures for the evaluation of novel antivirals and vaccines. Methods: We developed a composite clinical score based on extensive systematic literature review and WHO-criteria for uncomplicated and complicated influenza infection. Recognizing that data standardization is most challenging in infants and young children, the ViVI Disease Severity Score was first tested across the entire pediatric age spectrum and then extended to use in adults. The mobile application facilitates data entry in compliance with CDISC (Clinical Data Interchange Standards Consortium) terminologies and regulatory data standard requirements. Results: The Score was made available for validation in the context of a hospital-based quality improvement (QI) program encompassing 6073 children with ARI (mean age 3.13; S.D. 3.89; range: 0 to 18.79). QI staff scored patients within 3-6 minutes and obtained nasopharyngeal swab samples. The national reference center performed molecular diagnostics for influenza A and B, respiratory syncytial virus (RSV), adeno-, rhino-, boca-, metapneumo-, parainfluenza-, and coronaviruses. Blinded bioinformatics analysis revealed that ViVI Scores were strongly predictive of antibiotic and antiviral use, even though the prescribing physicians were unaware of the scoring and results. Average disease severity was highest with RSV, followed by metapneumovirus and influenza A (H3N2) infections. The model was validated in a European multi-center setting and is currently in use in community clinics in the New Orleans metropolitan area. Healthcare workers score patients (both children and adults) using the mobile app while rapid diagnostics for influenza and RSV (Sofia, Quidel Inc., San Diego, CA, USA) are underway. Rapid test results are transmitted wirelessly to the Louisiana Department of Health with severity scores being reported via mobile app. Conclusion: We report a first successful pilot program linking rapid diagnostics with instantaneous individual-level reporting of severity in patients with ARI using a digital, prospectively validated scoring system for children and adults. Real-time mapping of incidence and severity will provide timely information to hospital staff and public health stakeholders. Data standardization allows cross-cohort comparisons in single and multi-center settings, in full compliance with HIPPAA (U.S. Health Insurance Portability and Accountability Act) and regulatory data standards. Additional proof-of-concept studies are underway in Cambodia and other low-middle income countries.