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

Abstract 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 What is already known of this topic Cognitive difficulties and physical symptoms have been reported after infections with the SARS-CoV-2 virus, but lack of studies with data before and after infections have sparked a global debate regarding severity and duration of these symptoms. Post acute viral syndromes have been described after many different infections, but it is unknown whether the symptoms of “long-COVID” or Post Acute Sequela after COVID-19 (PASC) are specific to the SARS-CoV-2 or not. What this study adds We found a significant and long-term increase in cognitive symptoms, anosmia and dysgeusia, dyspnoea, fatigue, and self-assessed worsening of overall health after a positive (COVID-19) but not a negative (indication of another infection) SARS-CoV-2 test. To our knowledge, this is the first large cohort study to report the trajectories of both cognitive and physical symptoms from before and up to 22 months after a positive SARS-CoV-2 test, compared to SARS-CoV-2 negative controls.