Introduction. There is a lack of available data on the economic burden of wheezing episodes resulting from prior severe respiratory syncytial virus (RSV) infections in resource constrained settings. This study aimed to assess the cost incurred for wheezing episodes during five years after a severe RSV infection in children from Argentina, considering both the public health system and societal perspectives. Methods. A prospective cohort was conducted to assess the cost-of-illness (COI) linked to wheezing episodes after severe RSV disease in children from Buenos Aires, Argentina. Direct medical and non-medical costs were estimated, along with indirect costs per episode and patient. Data pertaining to healthcare resource utilization, indirect expenses, and parental out of pocket costs were obtained from research forms. The overall cost per hospitalization and health visits were calculated from the perspectives of the healthcare system and society. Costs were quantified in US dollars. Results. Overall, 150 children aged between 12 and 60 months presented a total of 429 wheezing episodes. The median number of wheezing episodes per patient was 5 (IQR 3 to 7). The mean cost per wheezing episode was US$ 191.01 (95% confidence interval [CI] $166.37 to $215.64). The total cost per episode of wheezing was significantly higher (p<0.001) in infants under 12 months of age (207.43, 95%CI 154.3-260.6) compared to older toddler subgroups. The average cumulative cost associated to wheezing per patient was US$ 415.99 (95%CI $313.35 to $518.63). Considering both acute RSV disease and long-term wheezing outcomes the cumulative mean cost per patient was US$ 959.56 (95%CI $832.01 to $1087.10). Conclusions. This study reveals the economic impact of prolonged wheezing resulting from severe acute RSV infection on Argentina's public health system and society. The estimates obtained serve as valuable inputs for informing cost effectiveness analyses of upcoming RSV preventive interventions.

Dr. Polack reports grants and personal fees from JANSSEN, PFIZER, SANOFI, and MERCK, outside the submitted work. Dr. Libster reports grants and/or personal fees from Merck, Pfizer, Janssen outside the submitted work. Elisabeth Vodicka was employed at PATH during her collaborations on this study; she is currently an employee of Pfizer. The rest of the authors declares no competing interests.

This work was supported by the Bill & Melinda Gates Foundation (Grant Number INV-007610). Under the grant conditions of the Bill & Melinda Gates Foundation, a Creative Commons Attribution 4.0 generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. The findings and conclusions contained within are those of the authors and do not necessarily reflect the positions or policies of the Bill & Melinda Gates Foundation.

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The institutional review boards at each participating hospital in the Province of Buenos Aires approved the study: Hospital Evita de Lanus(approval ID number: 028/21) and Hospital Evita Pueblo de Berazategui (approval ID number: 025/21). Informed consent was obtained from all participating parents or guardians.

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https://zenodo.org/records/10440099