Hospital admissions and need for mechanical ventilation in children with respiratory syncytial virus before and during the COVID-19 pandemic: a Danish nationwide cohort study.

BACKGROUND: The incidence of respiratory syncytial virus (RSV) increased in several countries after the relaxation of COVID-19 restrictions. We aimed to investigate the age-related risk of RSV-associated hospital admissions and need for mechanical ventilation during the RSV resurgence in summer and autumn 2021 compared with the four RSV seasons preceding the COVID-19 pandemic. We also aimed to describe the clinical complications necessitating mechanical ventilation. METHODS: This population-based cohort study included patients aged 0-17 years admitted to hospital with RSV in Denmark during the RSV resurgence in summer and autumn 2021, and the four pre-COVID-19 RSV seasons (2016-17, 2017-18, 2018-19, and 2019-20). We retrieved data on RSV-associated hospital admissions from the Danish National Patient Registry and demographic and clinical details of children who received mechanical ventilation through prospective real-time data collection in 2021-22 and retrospective data collection for the 2016-17 to 2019-20 RSV seasons from all eight paediatric and neonatal intensive care units in Denmark. Risk factors for severe RSV disease were as defined as age younger than 3 months or severe comorbidities. We calculated the risk of RSV-associated hospital admissions per 100 000 population in each RSV season from week 21 to week 20 of the following year. We also calculated the risk rate of receiving mechanical ventilation per 100 000 population and 1000 RSV-associated hospital admissions during each RSV season from week 21 to week 20 of the following year. We calculated risk ratios (RRs) for hospital admission and mechanical ventilation by dividing the risk rate of hospital admission and mechanical ventilation in 2021-22 by annual mean risk rates in the four pre-COVID-19 RSV epidemics (2016-17 to 2019-20). We compared RRs using Fisher's exact test. We compared complications leading to intubation between children with and without risk factors for severe RSV disease. The study is registered at ClinicalTrials.gov, NCT05186597. FINDINGS: Among 310 423 Danish children aged younger than 5 years, the mean number of RSV-associated hospital admissions increased from 1477 (SD 226) in the 2016-17 to 2019-20 RSV seasons to 3000 in the 2021-22 RSV season (RR 2·0 [95% CI 1·9-2·1]). 54 children with RSV received mechanical ventilation in 2021-22 compared with 15-28 annually in the 2016-17 to 2019-20 RSV seasons (2·3 [1·6-3·3]). The highest increase in hospital admissions and need for mechanical ventilation occurred among children aged 24-59 months (4·1 [3·6-4·7] for hospital admission; 4·6 [1·7-12·6] for mechanical ventilation). Among children admitted to hospital, the risk of mechanical ventilation was similar in 2021-22 and the four pre-COVID-19 seasons (risk rate 14·3 per 1000 RSV-associated hospital admissions [95% CI 10·4-19·3] vs 12·9 [10·1-16·1]; RR 1·1 [95% CI 0·8-1·6]). Across all RSV seasons studied, among children younger than 3 months or those with severe comorbidities, respiratory failure due to bronchiolitis led to mechanical ventilation in 69 (79%) of 87 children. Of 46 children with no risk factors for severe RSV, 40 (87%) received mechanical ventilation due to additional complications, including neurological (n=16; 35%), cardiac (n=1; 2%), and pulmonary complications (n=23; 50%; eg, wheeze responsive to bronchodilator therapy, severe bacterial co-infections, and pneumothorax). INTERPRETATION: In Denmark, RSV disease did not seem to be more severe for the individual child during the RSV resurgence in 2021 following relaxation of COVID-19 restrictions. However, hospital admissions were higher among older children, possibly due to a postponed first RSV infection or no recent reinfection. Older children without risk factors for severe RSV disease had atypical complications that led to intubation. 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. FUNDING: National Ministry of Higher Education and Science and the Innovation Fund Denmark.

Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) occurs after infection with SARS-CoV-2 and its incidence is likely to depend on multiple factors, including the variant of the preceding SARS-CoV-2 infection and vaccine effectiveness. We aimed to estimate the incidence of MIS-C, and describe the clinical phenotype, following the delta variant of SARS-CoV-2 (B.1.617.2 and sublineages) according to vaccination status. We aimed to compare the incidence and clinical phenotype of MIS-C from our cohort during the pre-delta era. METHODS: This prospective, population-based cohort study included patients aged 0-17 years hospitalised with MIS-C in Denmark, according to the US Centers for Disease Control and Prevention case definition, from Aug 1, 2021, to Feb 1, 2022, a period dominated by the delta variant. We identified MIS-C cases via a nationwide research collaboration involving real-time data collection from all 18 paediatric departments. Aggregated number of SARS-CoV-2 infections by vaccination status was obtained from the Danish COVID-19 surveillance registries. The incidence of MIS-C was calculated using the estimated number of infected individuals by vaccination status. We calculated the incidence of MIS-C per 1 000 000 vaccinated and unvaccinated person-years, and estimated vaccine effectiveness as 1-incidence rate ratio using Poisson regression. Incidence and phenotype of MIS-C were compared with MIS-C cases from the first year of the pandemic. This study is registered at ClinicalTrials.gov, NCT05186597. FINDINGS: We identified 51 MIS-C cases among unvaccinated individuals and one in a fully vaccinated adolescent. The incidence of MIS-C was one in 3400 unvaccinated individuals (95% CI 2600-4600) with the delta variant and one in 9900 vaccinated individuals (95% CI 1800-390 000) with breakthrough infection. The estimated vaccine effectiveness against MIS-C after the delta variant was 94% (95% CI 55-99; p=0·0061) in individuals aged 5-17 years. The clinical phenotype during the delta wave was comparable to the pre-delta era. INTERPRETATION: We found the incidence and phenotype of MIS-C in unvaccinated children during the delta wave to be similar to the incidence during the first year of the pandemic. We found vaccine effectiveness to be high against MIS-C, which we suggest was due to protection from infection and, possibly, a decreased incidence of MIS-C after breakthrough infection. Knowledge of the incidence of MIS-C after different SARS-CoV-2 variants and the effect of vaccination might contribute to the elucidation of the extent to which MIS-C is a vaccine-preventable disease. FUNDING: National Ministry of Higher Education and Science and Innovation Fund Denmark.

Population-based Incidence of Myopericarditis After COVID-19 Vaccination in Danish Adolescents.

In this prospective nationwide multicenter study from Denmark, myopericarditis after Pfizer-BioNTech mRNA COVID-19 vaccination was identified in 13 males and 2 females between May 15 and September 15, 2021, among 133,477 vaccinated males and 127,857 vaccinated females 12-17 years of age, equaling 97 males and 16 females per million. In conclusion, the incidence of myopericarditis after COVID-19 vaccination among males appears higher than reports from the United States.