PLoS Medicine (Nov 2022)

Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany.

  • Martin Roessler,
  • Falko Tesch,
  • Manuel Batram,
  • Josephine Jacob,
  • Friedrich Loser,
  • Oliver Weidinger,
  • Danny Wende,
  • Annika Vivirito,
  • Nicole Toepfner,
  • Franz Ehm,
  • Martin Seifert,
  • Oliver Nagel,
  • Christina König,
  • Roland Jucknewitz,
  • Jakob Peter Armann,
  • Reinhard Berner,
  • Marina Treskova-Schwarzbach,
  • Dagmar Hertle,
  • Stefan Scholz,
  • Stefan Stern,
  • Pedro Ballesteros,
  • Stefan Baßler,
  • Barbara Bertele,
  • Uwe Repschläger,
  • Nico Richter,
  • Cordula Riederer,
  • Franziska Sobik,
  • Anja Schramm,
  • Claudia Schulte,
  • Lothar Wieler,
  • Jochen Walker,
  • Christa Scheidt-Nave,
  • Jochen Schmitt

DOI
https://doi.org/10.1371/journal.pmed.1004122
Journal volume & issue
Vol. 19, no. 11
p. e1004122

Abstract

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BackgroundLong-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults.Methods and findingsWe used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28, 95% CI: 1.71 to 3.06, p ConclusionsIn this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults.Trial registrationClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.