Post COVID-19 in children, adolescents, and adults: results of a matched cohort study including more than 150,000 individuals with COVID-19

Roessler, M.; Tesch, F.; Batram, M.; Jacob, J.; Loser, F.; Weidinger, O.; Wende, D.; Vivirito, A.; Toepfner, N.; Seifert, M.; Nagel, O.; König, C.; Jucknewitz, R.; Armann, J. P.; Berner, R.; Treskova-Schwarzbach, M.; Hertle, D.; Scholz, S.; Stern, S.; Ballesteros, P.; Bassler, S.; Bertele, B.; Repschläger, U.; Richter, N.; Riederer, C.; Sobik, F.; Schramm, A.; Schulte, C.; Wieler, L.; Walker, J.; Scheidt-Nave, C.; Schmitt, J.

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 more than 45 percent of the German population from January 2019 through December 2020, we investigated post COVID-19 in children/adolescents and adults. Methods: From a total of 38 million individuals, we identified all patients with laboratory confirmed diagnosis of COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age, sex, and propensity score matching on prevalent medical conditions. COVID-19 and control cohorts were followed for incident morbidity outcomes documented at least three months after the date of COVID-19 diagnosis, which was used as the index date for both groups. Overall, 96 pre-defined outcomes were aggregated into 13 diagnosis/symptom complexes and three domains (physical health, mental health, physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95%-confidence intervals (95%-CI). Results: The study population included 157,134 individuals (11,950 children/adolescents and 145,184 adults) with confirmed COVID-19. COVID-19 and control cohort were well-balanced regarding covariates. For all health outcomes combined, incidence rates (IRs) in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR=1.30, 95%-CI=[1.25-1.35], IR COVID-19=436.91, IR Control=335.98) and adults (IRR=1.33, 95%-CI=[1.31-1.34], 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, incidence rates were significantly higher in all 13 diagnosis/symptom complexes in adults and in ten diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for the age groups 0-11 and 12-17. Incidence rates in children/adolescents were consistently lower than those in adults. Among the specific outcomes with the highest IRR and an incidence rate 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=[1.71-3.06], IR COVID-19=12.58, IR Control=5.51), cough (IRR=1.74, 95%-CI=[1.48-2.04], IR COVID-19=36.56, IR Control=21.06), and throat/chest pain (IRR=1.72, 95%-CI=[1.39-2.12], IR COVID-19=20.01, IR Control=11.66). In adults, these included dysgeusia (IRR=6.69, 95%-CI=[5.88-7.60], IR COVID-19=12.42, IR Control=1.86), fever (IRR=3.33, 95%-CI=[3.01-3.68], IR COVID-19=11.53, IR Control=3.46), and dyspnea (IRR=2.88, 95%-CI=[2.74-3.02], IR COVID-19=43.91, IR Control=15.27). Conclusions: This large, matched cohort study indicates substantial new-onset post COVID-19 morbidity in pediatric and adult populations based on routine health care documentation. Further investigation is required to assess the persistence and long-term health impact of post COVID-19 conditions, especially in children and adolescents.