Assessing the Long-Term Economic Impact of Wheezing Episodes After Severe RSV Disease in Children from Argentina: A Cost of Illness Analysis

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 3-7). The mean cost per wheezing episode was US$ 191.01 (95% confidence interval [CI] $166.37 – $215.64). The total cost per episode of wheezing was significantly higher (p<0.001) in infants under 12 months of age (207.43, 95%CI 154.3-260.6) compared to older toddler subgroups. The average cumulative cost associated to wheezing per patient was US$ 415.99 (95%CI $313.35 - $518.63). Considering both acute RSV disease and long-term wheezing outcomes the cumulative mean cost per patient was US$ 959.56 (95%CI $832.01-$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. What is already known on this topic Multiple studies demonstrate the association between severe acute lower respiratory tract infections caused by RSV in infancy with long-term obstructive pulmonary disease such as recurrent wheezing or asthma. Nevertheless, there is a lack of information regarding the economic impact of these frequent wheezing episodes in individuals who experienced hospitalization due to RSV disease early in life, particularly in low- and middle-income countries. To address this gap, we conducted a prospective cohort study to ascertain the cost of illness associated with wheezing episodes in children during their initial 5 years of life following a severe RSV infection within a low-income population in Buenos Aires, Argentina. What this study adds This study provides a comprehensive account of both medical and non-medical expenses associated with frequent wheezing episodes in childhood in low settings of Argentina, focusing on patients who experienced a severe RSV infection. Furthermore, we computed the total cost, encompassing the expenses associated with the initial severe RSV disease in those patients with long-term wheezing episodes. How this study might affect research, practice or policy The data produced in this study is important for estimating the economic impact of forthcoming preventive measures against RSV in low- and middle-income countries through cost-effectiveness studies. Health decision-makers can leverage this information for future decisions on implementing preventive policies against RSV in infancy. ### Competing Interest Statement 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. ### Funding Statement 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. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: 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. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets used and/or analyzed during the current study are available in Zenodo () or from the corresponding author. * RSV : respiratory syncytial virus ALRTI : acute lower respiratory tract infection CI : confidence interval COI : cost of illness ER : emergency room GLM : generalized linear model IQR : interquartile range LMICs : low- and middle-income countries OLS : ordinary least squares SD : standard deviations