Temporal trajectories of COVID-19 symptoms in adults with 22 months follow-up in a prospective cohort study in Norway.

Objectives We aimed to describe the trajectories of cognitive and physical symptoms before, during, and after a positive- or negative SARS-CoV-2 test and in untested controls. Design A prospective cohort study. Setting Norway, 27 March 2020 to 6 July 2022 Participants A total of 146 065 volunteers were recruited. Of these, 120 605 participants (mean age 49 (SD 13.7), 69% female), were initially untested for the SARS-CoV-2 virus, completed one or more follow-up questionnaires (response rates 72-90%) and were included for analysis. After 22 months of follow-up, 15 737 participants had a positive SARS-CoV-2 test, 67 305 a negative test, and 37 563 were still untested. Main outcome measures We assessed reported symptoms the past three weeks of memory or concentration problems, anosmia and dysgeusia, dyspnoea, fatigue, fever, headache, cough, muscular pain, nasal symptoms, sore throat and abdominal pain at baseline and through four follow-up questionnaires. In addition, overall health compared to a year before was measured with a five-point scale and memory problems were measured using the Everyday Memory Questionnaire-13 at two timepoints. The exposure, SARS-CoV-2 test status (positive, negative or untested), was obtained from a mandatory national registry or from self-report, and data were analysed using mixed model logistic regression. Results A positive SARS-CoV-2-test was associated with the following persistent symptoms, compared with participants with a negative test (1-3 months after a negative test); memory problems (3 to 6 months after a positive test: adjusted odds ratio (OR) 9.1, 95% confidence interval (CI) 7.5 to 10.9; 12 to 18 months: OR 7.8, CI 5.7 to 10.8), concentration problems (3 to 6 months: OR 6.1, CI 4.8 to 6.5; 12 to 18 months: OR 5.3, CI 3.9 to 7.1), anosmia and dysgeusia, dyspnoea and fatigue as well as self-assessed worsening of overall health. Conclusion A positive SARS-CoV-2 test was associated with new onset memory- and concentration problems, anosmia and dysgeusia, dyspnoea and fatigue as well as self-assessed worsening of overall health, which persisted for the length of the follow-up of 22 months, even when correcting for symptoms before COVID-19 and compared to symptoms in negative controls. Trial registration ClinicalTrials ID: [NCT04320732][1] ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This work was funded by the Research Council of Norway (no: 324274) and Southern and Eastern Norway Regional Health Authority (internal funding). The funder had no role in the conduction, collection of data or interpretation of results. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Norwegian Regional Committee for Research Ethics (REK 151 124170), and all participants submitted electronic informed consent forms. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04320732&atom=%2Fmedrxiv%2Fearly%2F2024%2F05%2F01%2F2024.04.30.24306604.atom