*Necessary notice: medRxiv publishes preliminary scientific reports that should not peer-reviewed and, due to this fact, mustn’t be thought to be conclusive, guide clinical practice/health-related behavior, or treated as established information.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 resulting from respiratory syncytial virus (RSV) infections to develop a clinical model for guiding immunization and prophylactic treatment of one-year-old infants against RSV infections.

Study: Risk aspects for severe respiratory syncytial virus infection through the first yr of life: development and validation of a clinical prediction model. Image Credit: ART-ur/Shutterstock

Background

Although RSV infects individuals of all age groups, it’s most prevalent in young children and results in severe infections of the lower respiratory tracts in infants below the age of 1. The worldwide annual mortality rate amongst children below the age of 5 is 100,000, and in colder countries, RSV causes an annual epidemic. While the disease mitigation measures enforced through 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 one available monoclonal antibody immunoprophylactic, and resulting from 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. Moreover, 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 aspects similar to preterm birth, congenital heart defects, bronchopulmonary dysplasia, neonatal respiratory problems, and environmental aspects similar to exposure to tobacco smoke have been identified as risk aspects. Nonetheless, the predictors for severe RSV infections that result in hospitalization remain unclear.

In regards to the study

In the current study, the researchers used Finland’s nationwide registry data to look at all children born between the start of June 1997 and the tip of May 2020, and their siblings and fogeys, to develop a clinical model to predict hospitalization with RSV bronchiolitis amongst children below the age of 1. Cases of death or infections in the primary week of life were excluded. The measured end result was hospitalization resulting from RSV infection diagnosed using the International Classification of Diseases, tenth revision (ICD-10) code, between the seventh and 365th 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 following RSV epidemic, occurrence of twins, birth weight, bronchopulmonary dysplasia, Down syndrome, congenital heart defects requiring surgery in the primary month, first yr, or after the primary yr of life, and the variety of siblings below the age of 4, between the ages of 4 and 7, and above the age of seven.

A complete 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 similar to a family history of asthma. National registers of medical birth information and congenital malformations were used to acquire information on the infants, while pregnancy-related registries, diagnoses, and prescription information were used to define the pregnancy-related variables.

Results

The outcomes reported that other than known predictors similar to severe congenital heart defects, novel predictors of RSV-associated hospitalization included esophageal malformations and congenital heart defects of lower complexities. Moreover, gestational age at birth, having young siblings, and time in months between birth and the occurrence of the following RSV epidemic were also strong population-level predictors of RSV-associated hospitalization. Birth before 29 weeks of gestation increased the chance of RSV-associated hospitalization by 4.2-fold in comparison with children who had term births, and infants who were two months old at the height of the following RSV epidemic had a 5.3-fold risk of hospitalization in comparison with 11-month-old infants.

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

Conclusions

Overall, the outcomes indicated that other than severe congenital heart defects, esophageal malformations that increase the chance of respiratory infections and pneumonia, and low complexity congenital heart defects were essential predictors of RSV-associated hospitalization at individual and population levels. These findings could be utilized in developing recommendations and guidelines for passive immunization and immunoprophylactic treatment against RSV infections.

*Necessary notice

medRxiv publishes preliminary scientific reports that should not peer-reviewed and, due to this fact, mustn’t be thought to be conclusive, guide clinical practice/health-related behavior, or treated as established information.

*Necessary notice: medRxiv publishes preliminary scientific reports that should not peer-reviewed and, due to this fact, mustn’t be thought to be conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

• Preliminary scientific report.
  Pekka Vartiainen, Sakari Jukarainen, Samuel Arthur Rhedin, Alexandra Prinz, Tuomo Hartonen, Andrius Vabalas, Essi Viippola, Rodosthenis S. Rodosthenous, Sara Kuitunen, Aoxing Liu, Cecilia Lundholm, Awad I. Smew, Emma Caffrey Osvald, Emmi Helle, Markus Perola, Catarina Almqvist, Santtu Heinonen, and Andrea Ganna. (2023). medRxiv. doi: https://doi.org/10.1101/2023.02.23.232862 https://www.medrxiv.org/content/10.1101/2023.02.23.23286237v1