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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Martin Roessler - , Center for Evidence-Based Healthcare, Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus Dresden (Author)
  • Falko Tesch - , Center for Evidence-Based Healthcare, Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus Dresden (Author)
  • Manuel Batram - , Bielefeld University (Author)
  • Josephine Jacob - , Charité – Universitätsmedizin Berlin (Author)
  • Friedrich Loser - , Techniker Krankenkasse (Author)
  • Oliver Weidinger - , AOK Bayern (Author)
  • Danny Wende - , Chair of Quantitative Methods, esp Econometrics, Barmer Institute for Health System Research and Barmer Statutory Health Insurance Fund, Free University of Berlin (Author)
  • Annika Vivirito - , Charité – Universitätsmedizin Berlin (Author)
  • Nicole Toepfner - , Department of Paediatrics, Innsbruck Medical University, University Hospital Carl Gustav Carus Dresden (Author)
  • Franz Ehm - , Center for Evidence-Based Healthcare, Chair of Business Administration, esp Industrial Management, Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus Dresden (Author)
  • Martin Seifert - , Center for Evidence-Based Healthcare, Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus Dresden (Author)
  • Oliver Nagel - , Charité – Universitätsmedizin Berlin (Author)
  • Christina König - , Techniker Krankenkasse (Author)
  • Roland Jucknewitz - , AOK Bayern (Author)
  • Jakob Peter Armann - , Department of Paediatrics, Innsbruck Medical University, University Hospital Carl Gustav Carus Dresden (Author)
  • Reinhard Berner - , Department of Paediatrics, Innsbruck Medical University, University Hospital Carl Gustav Carus Dresden (Author)
  • Marina Treskova-Schwarzbach - , Robert Koch-Institut (Author)
  • Dagmar Hertle - , Barmer Institute for Health System Research and Barmer Statutory Health Insurance Fund (Author)
  • Stefan Scholz - , Robert Koch-Institut (Author)
  • Stefan Stern - , AOK Bayern (Author)
  • Pedro Ballesteros - , Barmer Institute for Health System Research and Barmer Statutory Health Insurance Fund (Author)
  • Stefan Baßler - , AOK PLUS (Author)
  • Barbara Bertele - , Techniker Krankenkasse (Author)
  • Uwe Repschläger - , Barmer Institute for Health System Research and Barmer Statutory Health Insurance Fund (Author)
  • Nico Richter - , DAK-Gesundheit, Hamburg, Germany. (Author)
  • Cordula Riederer - , DAK-Gesundheit, Hamburg, Germany. (Author)
  • Franziska Sobik - , DAK-Gesundheit, Hamburg, Germany. (Author)
  • Anja Schramm - , Center for Evidence-Based Healthcare, AOK Bayern, University Hospital Regensburg (Author)
  • Claudia Schulte - , Barmer Institute for Health System Research and Barmer Statutory Health Insurance Fund (Author)
  • Lothar Wieler - , Robert Koch-Institut (Author)
  • Jochen Walker - , Charité – Universitätsmedizin Berlin (Author)
  • Christa Scheidt-Nave - , Robert Koch-Institut (Author)
  • Jochen Schmitt - , Center for Evidence-Based Healthcare, Center for Evidence-Based Healthcare, University Hospital Carl Gustav Carus Dresden (Author)

Abstract

BACKGROUND: Long-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 FINDINGS: We 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 < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30, 95% CI: 1.25 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias.

CONCLUSIONS: In 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 REGISTRATION: ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.

Details

Original languageEnglish
Pages (from-to)e1004122
JournalPLoS medicine
Volume19
Issue number11
Publication statusPublished - Nov 2022
Peer-reviewedYes

External IDs

PubMedCentral PMC9648706
Scopus 85141893114

Keywords

Sustainable Development Goals

Keywords

  • Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Cohort Studies, COVID-19/epidemiology, COVID-19 Testing, Germany/epidemiology, Morbidity, Retrospective Studies, Young Adult, Middle Aged, Post-Acute COVID-19 Syndrome

Library keywords