Interventions to Delay Primary RSV May Increase Risk for Severe Infection

Respiratory syncytial virus (RSV)-associated hospital admissions and mechanical ventilation significantly increased after the relaxation of COVID-19 restrictions, particularly among older children and those with no risk factors for severe infection. These study results, published in The Lancet Child and Adolescent Health, suggest interventions that delay primary RSV infection occurrence may increase the number of older children at risk for severe infection.

Researchers conducted a population-based cohort study in Denmark to assess the age-related risk for RSV-associated hospital admissions and mechanical ventilation during the RSV resurgence from 2021 to 2022 compared with the 4 RSV seasons prior to the COVID-19 pandemic. Prospective data from the 2021 to 2022 RSV season and retrospective data from the 2016 to 2017 and 2019 to 2020 seasons were sourced from the Danish National Patient Registry. Risk ratios (RRs) were calculated via Fisher exact testing. The researchers also compared complications necessitating intubation between children with vs without risk factors for severe RSV infection.

The final analysis included patients aged between 0 and 17 years. Among 310,423 children younger than 5 years, the mean (SD) number of RSV-associated hospital admissions increased from 1477 (266) in the 2016 to 2017 and  2019 to 2020 RSV seasons to 3000 in the 2021 to 2022 season.

The risk for RSV-associated hospitalization per 100,000 people also increased from 476 in the 2016 to 2017 and 2019 to 2020 seasons (95% CI, 464-488) to 966 (95% CI, 932-1001) in the 2021 to 2022 (RR, 2.0; 95% CI, 1.9-2.1; P <.0001). Further comparisons between these time periods showed children aged 48  to 59 months had the most significantly increased risk for RSV-associated hospital admissions among all age groups (RR, 5.5; 95% CI, 3.8-8.3; P <.0001).

The number of children younger than 5 years of age who required mechanical ventilation doubled during the 2021 to 2022 RSV resurgence (n=54) compared with the previous 4 RSV seasons (n=15-28).

The overall population-based risk for requiring mechanical ventilation was also 2.3-times higher (95% CI, 1.6-3.3; P <.0001) in the 2021 to 2022 season compared with the previous 4 RSV seasons. This increase in mechanical ventilation risk observed between these periods was also significant when the analysis was restricted to patients younger than 3 months (RR, 2.2; 95% CI, 1.3-3.7; P =.007) and those aged 24 to 59 months (RR, 4.6; 95% CI, 1.7-12.6; P =.004).

Further analysis showed children with no risk factors for severe infection had an increased risk for atypical complications leading to mechanical ventilation when compared with those at risk for severe infection. Of 46 children with no risk factors, 87% required mechanical ventilation due to bacterial pneumonia, pneumothorax, cardiac-related complications, bronchodilator-responsive wheezing, and neurologic-related complications.

Study limitations include the inability to determine the absolute total number of RSV infections, including in the outpatient setting. The researchers also noted that RSV testing is performed only in the hospital setting in Denmark. 

According to the researchers, “If new RSV-preventive interventions for healthy infants delay first RSV infection, a higher number of older children might be admitted to hospital due to atypical clinical phenotypes, rather than classical bronchiolitis.”