COVID-19 illness severity and 2-year prevalence of physical symptoms: an observational study in Iceland, Sweden, Norway and Denmark
Authors: Shen Qing , Joyce Emily E. , Ebrahimi Omid V. , Didriksen Maria , Lovik Anikó , Sævarsdóttir Karen Sól , Magnúsdóttir Ingibjörg , Mikkelsen Dorte Helenius , Unnarsdóttir Anna Bára , Hauksdóttir Arna , Hoffart Asle , Kähler Anna K. , Thórdardóttir Edda Björk , Eythórsson Elías , Frans Emma M. , Tómasson Gunnar , Ask Helga , Hardardóttir Hrönn , Jakobsdóttir Jóhanna , Lehto Kelli , Lu Li , Andreassen Ole A. , Sullivan Patrick F. , Pálsson Runólfur , Erikstrup Christian , Ostrowski Sisse Rye , Werge Thomas , Aspelund Thor , Pedersen Ole B. V. , Johnson Sverre Urnes , Fang Fang , Valdimarsdóttir Unnur Anna 
Published: April 2023

AbstractBackgroundPersistence of physical symptoms after SARS-CoV-2 infection is a major public health concern, although evidence from large observational studies 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.MethodsThis 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.FindingsDuring up to 27 months of follow-up, 22 382 participants (34.5%) 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.InterpretationThese 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.FundingThis work was mainly supported by grants from NordForsk (COVIDMENT, grant number 105668 and 138929) and Horizon2020 (CoMorMent, 847776). See Acknowledgements for further details on funding.Research in contextEvidence before the studyAs the majority of the global population has contracted COVID-19, persistence of physical symptoms after SARS-CoV-2 infection (LongCOVID or post COVID-19 condition) has become a major public health concern. We searched PubMed for studies assessing physical symptoms after COVID-19, published by March 22, 2023. The search term was (physical symptoms after covid) AND LitCLONGCOVID [Pubmed filter]. We reviewed 82 studies, after excluding those not on humans or not published in English. High prevalence of multiple physical symptoms, mainly fatigue, shortness of breath, headache, muscle and chest pain, has been reported, mostly based on small samples of hospitalized patients confined to three to six months after diagnosis. A comprehensive assessment of long-term prevalence of physical symptoms beyond six months after diagnosis and among non-hospitalized patients is lacking.Added value of this studyWe included 64 880 participants from the general population of four Nordic countries, of whom 22 382 had been diagnosed with COVID-19 up to 2 years earlier (<1% hospitalized due to COVID-19). Individuals diagnosed with COVID-19 reported a 37% higher prevalence of overall severe physical symptom burden compared to individuals not diagnosed with COVID-19. We found that shortness of breath, chest pain, dizziness, headaches, and low energy/fatigue were particularly increased among individuals with COVID-19 diagnosis. Individuals bedridden for seven days or more during the acute illness phase (9.6% of the patients) showed the greatest and most persistent elevation in prevalence of severe physical symptoms while individuals not bedridden during the acute COVID-19 illness showed no increase in prevalence of physical symptoms compared to those not diagnosed.Implications of the available evidenceOur findings provide timely and valuable evidence to demonstrate the constitution of Long COVID and the long-term health consequences after recovery from COVID-19 in the general population. The long-term risk of severe physical symptom burden is distinctly associated with acute illness severity, highlighting the importance of sustained monitoring of physical symptoms among the group of patients who suffered severe acute illness course.