COVID-19 illness severity and 2-year prevalence of physical symptoms: an observational study in Iceland, Sweden, Norway and Denmark

Qing Shen; Emily E Joyce; Omid V Ebrahimi; Maria Didriksen; Anikó Lovik; Karen Sól Sævarsdóttir; Ingibjörg Magnúsdóttir; Dorte Helenius Mikkelsen; Anna Bára Unnarsdóttir; Arna Hauksdóttir; Asle Hoffart; Anna K Kähler; Edda Björk Thórdardóttir; Elías Eythórsson; Emma M Frans; Gunnar Tómasson; Helga Ask; Hrönn Hardardóttir; Jóhanna Jakobsdóttir; Kelli Lehto; Li Lu; Ole A Andreassen; Patrick F Sullivan; Runólfur Pálsson; Christian Erikstrup; Sisse Rye Ostrowski; Thomas Werge; Thor Aspelund; Ole B V Pedersen; Sverre Urnes Johnson; Fang Fang; Unnur Anna Valdimarsdóttir

doi:10.1016/j.lanepe.2023.100756

COVID-19 illness severity and 2-year prevalence of physical symptoms: an observational study in Iceland, Sweden, Norway and Denmark

Lancet Reg Health Eur. 2023 Oct 27:35:100756. doi: 10.1016/j.lanepe.2023.100756. eCollection 2023 Dec.

Authors

Qing Shen^{1

2

3

4}, Emily E Joyce⁴, Omid V Ebrahimi^{5

6}, Maria Didriksen⁷, Anikó Lovik^{4

8}, Karen Sól Sævarsdóttir³, Ingibjörg Magnúsdóttir³, Dorte Helenius Mikkelsen^{9

10}, Anna Bára Unnarsdóttir³, Arna Hauksdóttir³, Asle Hoffart⁶, Anna K Kähler¹¹, Edda Björk Thórdardóttir^{3

12}, Elías Eythórsson¹³, Emma M Frans¹¹, Gunnar Tómasson^{3

13}, Helga Ask^{5

14}, Hrönn Hardardóttir¹³, Jóhanna Jakobsdóttir³, Kelli Lehto¹⁵, Li Lu^{16

17

14}, Ole A Andreassen^{17

18}, Patrick F Sullivan^{11

19}, Runólfur Pálsson^{13

20}, Christian Erikstrup⁷, Sisse Rye Ostrowski^{7

21}, Thomas Werge^{9

10

21

22}, Thor Aspelund^{3

23}, Ole B V Pedersen^{21

24}, Sverre Urnes Johnson^{5

6}, Fang Fang⁴, Unnur Anna Valdimarsdóttir^{3

4

25}

Affiliations

¹ Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, China.
² Institute for Advanced Study, Tongji University, Shanghai, China.
³ Centre of Public Health Sciences, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
⁴ Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Psychology, University of Oslo, Oslo, Norway.
⁶ Modum Bad Psychiatric Hospital and Research Center, Vikersund, Norway.
⁷ Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁸ Methodology and Statistics Unit, Institute of Psychology, Leiden University, Leiden, the Netherlands.
⁹ Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁰ The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen and Aarhus, Denmark.
¹¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹² Mental Health Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
¹³ Internal Medicine and Emergency Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland.
¹⁴ Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
¹⁵ Estonian Genome Centre, Institute of Genomics, University of Tartu, Estonia.
¹⁶ Institute of Health Management and Policy, School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an, China.
¹⁷ NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁸ NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁹ Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, North Carolina, USA.
²⁰ Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
²¹ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²² Lundbeck Foundation Center for GeoGenetics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.
²³ The Icelandic Heart Association, Kopavogur, Iceland.
²⁴ Department of Clinical Immunology, Zealand University Hospital, Denmark.
²⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Abstract

Background: Although the persistence of physical symptoms after SARS-CoV-2 infection is a major public health concern, evidence from large observational studies beyond one year post diagnosis remain scarce. We aimed to assess the prevalence of physical symptoms in relation to acute illness severity up to more than 2-years after diagnosis of COVID-19.

Methods: This multinational study included 64,880 adult participants from Iceland, Sweden, Denmark, and Norway with self-reported data on COVID-19 and physical symptoms from April 2020 to August 2022. We compared the prevalence of 15 physical symptoms, measured by the Patient Health Questionnaire (PHQ-15), among individuals with or without a confirmed COVID-19 diagnosis, by acute illness severity, and by time since diagnosis. We additionally assessed the change in symptoms in a subset of Swedish adults with repeated measures, before and after COVID-19 diagnosis.

Findings: During up to 27 months of follow-up, 34.5% participants (22,382/64,880) were diagnosed with COVID-19. Individuals who were diagnosed with COVID-19, compared to those not diagnosed, had an overall 37% higher prevalence of severe physical symptom burden (PHQ-15 score ≥15, adjusted prevalence ratio [PR] 1.37 [95% confidence interval [CI] 1.23-1.52]). The prevalence was associated with acute COVID-19 severity: individuals bedridden for seven days or longer presented with the highest prevalence (PR 2.25 [1.85-2.74]), while individuals never bedridden presented with similar prevalence as individuals not diagnosed with COVID-19 (PR 0.92 [0.68-1.24]). The prevalence was statistically significantly elevated among individuals diagnosed with COVID-19 for eight of the fifteen measured symptoms: shortness of breath, chest pain, dizziness, heart racing, headaches, low energy/fatigue, trouble sleeping, and back pain. The analysis of repeated measurements rendered similar results as the main analysis.

Interpretation: These data suggest an elevated prevalence of some, but not all, physical symptoms during up to more than 2 years after diagnosis of COVID-19, particularly among individuals suffering a severe acute illness, highlighting the importance of continued monitoring and alleviation of these targeted core symptoms.

Funding: This work was mainly supported by grants from NordForsk (COVIDMENT, grant number 105668 and 138929) and Horizon 2020 (CoMorMent, 847776). See Acknowledgements for further details on funding.

Keywords: COVID-19; Cohort; Long covid; Physical symptom.