Novel predictors of severe respiratory syncytial virus infections among infants below the age of one

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

In a recent study posted to the medRxiv* preprint server, researchers examined predictors for hospitalization due to respiratory syncytial virus (RSV) infections to develop a clinical model for guiding immunization and prophylactic treatment of one-year-old infants against RSV infections.

Background

Although RSV infects individuals of all age groups, it is most prevalent in young children and leads to severe infections of the lower respiratory tracts in infants below the age of one. The global annual mortality rate among children below the age of five is 100,000, and in colder countries, RSV causes an annual epidemic. While the disease mitigation measures enforced during the coronavirus disease 2019 (COVID-19) pandemic disrupted the annual epidemic patterns of RSV, after the pandemic-associated restrictions on movement and social interactions were lifted, stronger and earlier occurrences of RSV epidemics have been observed between 2021 and 2022.

Hitherto, palivizumab was the only available monoclonal antibody immunoprophylactic, and due to the high cost and difficult administration process, it was only prescribed in high-risk cases. Recently the European Medicines Agency has approved a single injection monoclonal antibody treatment Nirsevimab to treat RSV infections. Additionally, maternal RSV vaccines that act through the placental transfer of antibodies have shown some success. While age is a determinant of RSV infection severity, other factors such as preterm birth, congenital heart defects, bronchopulmonary dysplasia, neonatal respiratory problems, and environmental factors such as exposure to tobacco smoke have been identified as risk factors. However, the predictors for severe RSV infections that lead to hospitalization remain unclear.

About the study

In the present study, the researchers used Finland’s nationwide registry data to examine all children born between the beginning of June 1997 and the end of May 2020, and their siblings and parents, to develop a clinical model to predict hospitalization with RSV bronchiolitis among children below the age of one. Cases of death or infections in the first week of life were excluded. The measured outcome was hospitalization due to RSV infection diagnosed using the International Classification of Diseases, tenth revision (ICD-10) code, between the seventh and 365^th day of age.

Fourteen predefined predictors were identified based on literature and the screening for other predictors of RSV-associated hospitalization was conducted while controlling for these 14 predictors. These 14 predictors included gestational age at birth, mother’s age at birth, father’s age at birth, time in months between birth and the next RSV epidemic, occurrence of twins, birth weight, bronchopulmonary dysplasia, Down syndrome, congenital heart defects requiring surgery in the first month, first year, or after the first year of life, and the number of siblings below the age of four, between the ages of four and seven, and above the age of seven.

A total of 1510 candidate predictors were identified, comprising 487, 434, and 314 predictors related to the mother, father, and siblings, respectively, 166 predictors related to the pregnancy, 92 related to the infant’s health, and three composite variables such as a family history of asthma. National registers of medical birth information and congenital malformations were used to obtain information on the infants, while pregnancy-related registries, diagnoses, and prescription information were used to define the pregnancy-related variables.

Results

The results reported that apart from known predictors such as severe congenital heart defects, novel predictors of RSV-associated hospitalization included esophageal malformations and congenital heart defects of lower complexities. Additionally, gestational age at birth, having young siblings, and time in months between birth and the occurrence of the next RSV epidemic were also strong population-level predictors of RSV-associated hospitalization. Birth before 29 weeks of gestation increased the risk of RSV-associated hospitalization by 4.2-fold compared to children who had term births, and infants who were two months old at the peak of the next RSV epidemic had a 5.3-fold risk of hospitalization compared to 11-month-old infants.

Lower complexity congenital heart defects such as atrial and ventricular septal defects were thought to contribute significantly to the population-level burden of RSV infections. The authors believe that these low-complexity congenital heart defects were important predictors to be considered while making population-level immunization decisions. Additionally, Down syndrome was seen to influence the predisposition to severe RSV infections requiring hospitalization.

Conclusions

Overall, the results indicated that apart from severe congenital heart defects, esophageal malformations that increase the risk of respiratory infections and pneumonia, and low complexity congenital heart defects were important predictors of RSV-associated hospitalization at individual and population levels. These findings can be used in developing recommendations and guidelines for passive immunization and immunoprophylactic treatment against RSV infections.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.