Heterogeneity of Clinical Phenotypes in Severe Acute Respiratory Infections due to Respiratory Syncytial Virus: A Need to Look Beyond Hospitalization.

Objective: To use a pre-COVID-19 birth cohort database to describe the clinical heterogeneity of severe acute respiratory infections (SARI) cases of the past seasons as a basis to investigate further distribution of clinical phenotypes in the era of immunization for respiratory syncytial virus (RSV).

Study design: Infants with RSV-SARI were identified from a 2014 through 2019 birth cohort in a tertiary care center in Lyon, France, and their medical records extensively reviewed. Using the criteria of the World Health Organization severity definitions, we classified SARI as having nutritional (inability to feed), respiratory (SpO₂<93%), or neurological (failure to respond, apneas) impairments.

Results: We described three phenotypes: nutritional impairment, respiratory impairment, and neurological (with respiratory and nutritional) impairment. Respiratory impairment could overlap with nutritional impairment, or not. There was a significant difference in age categories distribution regarding nutritional impairment (greater proportion in 1.5- to 3-month-old, p=0.01) and neurological impairment (greater proportion in <1.5-month-old, p=0.002).

Conclusions: The present study highlights the presence of three potentially overlapping phenotypes as a new way to consider and describe RSV disease. In order to adapt care and healthcare policies in the RSV-immunization era, it is necessary to investigate further and monitor the residual SARI burden of each phenotype.