Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children From Wild-type to Population Immunity:A Prospective Multicenter Cohort Study With Real-time Reporting

BACKGROUND: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. METHODS: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. RESULTS: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. CONCLUSIONS: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections.</p

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children From Wild-type to Population Immunity:A Prospective Multicenter Cohort Study With Real-time Reporting

BACKGROUND: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. METHODS: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. RESULTS: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. CONCLUSIONS: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections.</p

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children from Wild-type to Population Immunity: A Prospective Multicenter Cohort Study with Real-time Reporting

Background: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. Methods: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. Results: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. Conclusions: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections

Daily intranasal palivizumab to prevent respiratory syncytial virus infection in healthy preterm infants: a phase 1/2b randomized placebo-controlled trialResearch in context

Summary: Background: Mucosal administration of monoclonal antibodies (mAbs) against respiratory pathogens is a promising alternative for systemic administration because lower doses are required for protection. Clinical development of mucosal mAbs is a highly active field yet clinical proof-of-concept is lacking. Methods: In this investigator-initiated, double-blind, randomized placebo-controlled trial, we evaluated intranasal palivizumab for the prevention of RSV infection in preterm infants (Dutch Trial Register NTR7378 and NTR7403). We randomized infants 1:1 to receive intranasal palivizumab (1 mg/mL) or placebo once daily during the RSV season. Any RSV infection was the primary outcome and RSV hospitalization was the key secondary outcome. The primary outcome was analyzed with a mixed effect logistic regression on the modified intention-to-treat population. Findings: We recruited 268 infants between Jan 14, 2019 and Jan 28, 2021, after which the trial was stopped for futility following the planned interim analysis. Adverse events were similar in both groups (22/134 (16.4%) palivizumab arm versus 26/134 (19.4%) placebo arm). There were 6 dropouts and 168 infants were excluded from the efficacy analyses due to absent RSV circulation during the SARS-CoV-2 pandemic. Any RSV infection was similar in infants in both groups (18/47 (38.3%) palivizumab arm versus 11/47 (23.4%) placebo arm; aOR 2.2, 95% CI 0.7–6.5). Interpretation: Daily intranasal palivizumab did not prevent RSV infection in late preterm infants. Our findings have important implications for the clinical development of mucosal mAbs, namely the necessity of timely interim analyses and further research to understand mucosal antibody half-life. Funding: Funded by the Department of Pediatrics, University Medical Centre Utrecht, the Netherlands