The magnitude and severity of paediatric RSV infections in 2022–2023: A Danish nationwide cohort study

A summer respiratory syncytial virus (RSV) resurgence occurred in many countries in 2021 after most COVID19 restrictions were lifted.1,2 In Denmark, the highest increase in hospital admissions and need for mechanical ventilation was in children aged 2– 5 years.3 The magnitude of the RSV epidemic was attributed to an immunity debt caused by the COVID19 lockdown.2 In 2022, the Danish RSV epidemic started in August, in contrast to the usual start in November, and peaked in October.4 We aimed to describe the agerelated risk of RSVassociated hospital admissions and need for mechanical ventilation in 2022– 2023. This nationwide populationbased cohort study prospectively included clinical data from patients aged 0– 5 years with RSV who received mechanical ventilation from week 21, 2022, to week 3, 2023. We retrieved data on RSVassociated hospital admissions from the Danish National Patient Registry during the same period. RSVassociated hospital admission was defined as admission for 12 h or more and a positive sample for RSV during admission and/ or 5 days or less before. Previously reported data during the four preCOVID19 seasons from 2016– 2017 to 2019– 2020 and in 2021– 2022 were used to compare RSV seasons.3 We calculated the risk of RSVassociated hospital admission and the need for mechanical ventilation per 100 000 children below 5 years in 2022– 2023. Fisher's exact test was used to compare the risks to the previous RSV seasons in risk ratios (RRs). Permission to disclose patient data was obtained through oral and written parental consent or a requirement waiver. Among 310 423 Danish children younger than 5 years, RSVassociated hospital admissions were 2435 in 2022– 2023, which was 1.7fold (95% CI, 1.6– 1.7) higher than in the four preCOVID19 seasons (Table 1). In infants below 3 months, the risk was 1.9 (RR, 1.9; 95% CI, 1.8– 2.0). The median age of hospitalised children in 2022– 2023 was equal to the preCOVID19 RSV seasons and significantly lower than in 2021– 2022 (Table 1). Twentynine children received mechanical ventilation in 2022– 2023, i.e., 1.2% (95%, CI 0.8– 1.7) of hospitalised children. This was similar to 1.2% (95% CI 1.0– 1.5; p = 0.913) in the preCOVID19 seasons and to 1.4% (95% CI 1.0– 1.8; p = 0.629) in 2021– 2022. Among children receiving mechanical ventilation, the proportion of children with risk factors for severe RSV disease (age below 3 months and/or comorbidities) was similar in 2022– 2023 compared with 2016– 2017 to 2019– 2020 (71% vs. 66%, p = 0.546) and 2021– 2022 (71% vs. 65%, p = 0.587). In children younger than 3 months or those with severe comorbidities, respiratory failure due to bronchiolitis led to mechanical ventilation, while previously healthy children had respiratory failure due to additional complications, including wheeze responsive to bronchodilator therapy (n = 4), severe bacterial coinfection (n = 1), pneumothorax (n = 1), and RSVassociated CNS complications (n = 2). In this nationwide populationbased cohort study, we found an almost twofold increase in hospital admissions during the RSV epidemic in 2022– 2023, compared with the preCOVID19 RSV epidemics. The twofold increase in hospital admissions was unexpected as high population immunity could have been expected following the extensive RSV resurgence in 2021. The median age among children below 5 years in 2022– 2023 was similar to the preCOVID19 seasons. This contrasted with the 2021– 2022 season, where the median age was significantly higher than in the preCOVID19 seasons.1– 3 This may reflect that the proportion of RSV naïve older children, and children with waning immunity due to no recent reinfection, was significantly lower in 2022– 2023 compared with 2021– 2022. In addition, a high increase in hospital admissions occurred in infants below 3 months in 2022– 2023, which may reflect reduced maternally derived RSV antibodies due to a specific immune debt in pregnant women. The severity of RSV disease for the individual child was perceived to be unchanged across all RSV seasons since the risk of mechanical ventilation among hospitalised children was similar in 2022– 2023 compared with previous seasons. In 2022– 2023, previously healthy children with no risk factors for severe RSV infection had atypical complications leading to mechanical ventilation, eg., wheeze responsive to bronchodilator therapy, as described in previous RSV epidemics.3 The main limitation of this study was the use of RSVassociated hospital admissions as a surrogate for the epidemic. Furthermore, it cannot be excluded that the increase in hospital admissions in 2022– 2023 partly was due to an increase in RSV testing practice. However, the weekly RSV testing rate in Denmark in 2022– 2023 was similar to the prepandemic testing rates.4 Furthermore, the weekly positivity rate among children below 5 years was equal across RSV seasons.5 The main strength was the nationwide prospective research setup in the very wellregistered Danish population.