Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study
Anneke Haddad,
Aleš Janda,
Hanna Renk,
Maximilian Stich,
Pauline Frieh,
Klaus Kaier,
Florens Lohrmann,
Alexandra Nieters,
Anna Willems,
Daniela Huzly,
Alex Dulovic,
Nicole Schneiderhan-Marra,
Eva-Maria Jacobsen,
Dorit Fabricius,
Maria Zernickel,
Thomas Stamminger,
Sebastian F.N. Bode,
Theda Himpel,
Jonathan Remppis,
Corinna Engel,
Andreas Peter,
Tina Ganzenmueller,
Georg Friedrich Hoffmann,
Bettina Haase,
Hans-Georg Kräusslich,
Barbara Müller,
Axel R. Franz,
Klaus-Michael Debatin,
Burkhard Tönshoff,
Philipp Henneke,
Roland Elling
Affiliations
Anneke Haddad
Center for Pediatrics and Adolescent Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
Aleš Janda
Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm University, Germany
Hanna Renk
University Children's Hospital Tuebingen, Tuebingen, Germany
Maximilian Stich
Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany
Pauline Frieh
Center for Pediatrics and Adolescent Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
Klaus Kaier
Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
Florens Lohrmann
Center for Pediatrics and Adolescent Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; IMM-PACT Clinician Scientist Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Alexandra Nieters
Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Anna Willems
Center for Pediatrics and Adolescent Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
Daniela Huzly
Institute of Virology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany
Alex Dulovic
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
Nicole Schneiderhan-Marra
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
Eva-Maria Jacobsen
Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm University, Germany
Dorit Fabricius
Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm University, Germany
Maria Zernickel
Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm University, Germany
Thomas Stamminger
Institute of Virology, Ulm University Medical Center, Ulm, Germany
Sebastian F.N. Bode
Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm University, Germany
Theda Himpel
University Children's Hospital Tuebingen, Tuebingen, Germany
Jonathan Remppis
University Children's Hospital Tuebingen, Tuebingen, Germany
Corinna Engel
Centre for Paediatric Clinical Studies, University Children's Hospital Tübingen, Tübingen, Germany
Andreas Peter
Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, Tübingen, Germany
Tina Ganzenmueller
Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany
Georg Friedrich Hoffmann
Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany
Bettina Haase
Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany
Hans-Georg Kräusslich
Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg, Germany
Barbara Müller
Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg, Germany
Axel R. Franz
University Children's Hospital Tuebingen, Tuebingen, Germany; Centre for Paediatric Clinical Studies, University Children's Hospital Tübingen, Tübingen, Germany
Klaus-Michael Debatin
Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm University, Germany
Burkhard Tönshoff
Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany
Philipp Henneke
Center for Pediatrics and Adolescent Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Roland Elling
Center for Pediatrics and Adolescent Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Corresponding author at: Center for Pediatrics and Adolescent Medicine, Medical Center, Faculty for Medicine, University of Freiburg, Mathildenstraβe 1, 79106 Freiburg, Germany.
Summary: Background: Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households. Methods: 1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires. Findings: The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% [95% CI: 30.7–42.4%] vs 14.2% [95% CI: 8.7–21.5%]), infected men (22.9% [95% CI: 17.9–28.5%] vs 10.3% [95% CI: 5.8–16.9%]) and infected adolescent girls (32.1% 95% CI: 17.2–50.5%] vs 8.9% [95%CI: 3.1–19.8%]). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14–18 (9.7% [95% CI: 2.8–23.6%] or in infected children <14 years (girls: 4.3% [95% CI: 1.2–11.0%]; boys: 3.7% [95% CI: 1.1–9.6%]) than in their exposed counterparts (adolescent boys: 0.0% [95% CI: 0.0–6.7%]; girls < 14 years: 2.3% [95% CI: 0·7–6·1%]; boys < 14 years: 0.0% [95% CI: 0.0–2.0%]). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI [1.03–1.20]). Interpretation: In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful. Funding: Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.
