Excess risk and clusters of symptoms after COVID-19 in a large Norwegian cohort

  1. Ida Henriette Caspersen
  2. Per Magnus
  3. Lill Trogstad

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Abstract

Physical, psychological and cognitive symptoms have been reported as post-acute sequelae for COVID-19 patients but are also common in the general uninfected population. We aimed to calculate the excess risk and identify patterns of 22 symptoms up to 12 months after COVID-19. We followed more than 70,000 adult participants in an ongoing cohort study, the Norwegian Mother, Father and Child Cohort Study (MoBa) during the COVID-19 pandemic. Infected and non-infected participants registered presence of 22 different symptoms in March 2021. One year after infection, 13 of 22 symptoms were associated with SARS-CoV-2 infection, based on relative risks between infected and uninfected subjects. For instance, 17.4% of SARS-CoV-2 infected cohort participants reported fatigue that persist 12 months after infection, compared to new occurrence of fatigue that had lasted less than 12 months in 3.8% of non-infected subjects (excess risk 13.6%). The adjusted relative risk for fatigue was 4.8 (95% CI 3.5–6.7). Two main underlying factors explained 50% of the variance in the 13 symptoms. Brain fog, poor memory, dizziness, heart palpitations, and fatigue had high loadings on the first factor, while shortness-of breath and cough had high loadings on the second factor. Lack of taste and smell showed low to moderate correlation to other symptoms. Anxiety, depression and mood swings were not strongly related to COVID-19. Our results suggest that there are clusters of symptoms after COVID-19 due to different mechanisms and question whether it is meaningful to describe long COVID as one syndrome.

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  1. Version published to 10.1007/s10654-022-00847-8
  2. ScreenIT

    SciScore for 10.1101/2021.10.15.21265038: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableParticipants were recruited from all over Norway from 1999-2008.4 The women consented to participation in 41% of the pregnancies and the cohort now includes 95,000 mothers and 75,000 fathers.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study has limitations. If we compare the prevalence of symptoms in Wave-1 and Wave-2 subjects, and make inferences about the duration of symptoms, there are important assumptions. One is that the type of coronavirus may have changed over time, so that the infection, at least theoretically, may have different long-term consequences. The other factor is that testing opportunities were more restricted during the spring of 2020 compared to later months, possibly inducing differential selection for Wave-1 and Wave-2 subjects. These limitations will be overcome as we continue follow-up in MoBa, since viral sequencing has become prevalent, and the same individuals will be followed. The symptoms in this study are self-reported in questionnaires, which has both advantages and draw-backs. The advantage is that one can ask a large, representative sample simple questions in a design that measures the prevalence, duration and correlational structure of symptoms, as well as the degree of association to prior infection. This type of data provides a supplement to what can be learned from linking population samples to health care registrations, as is done, for instance, in the follow-up of veterans in the US13. The draw-back is the lack of detail for each participant. There is a possibility for misclassification for signs or diseases that are not easily recognized by the study participants, like myocarditis and kidney disease, as we did not have objective measurements to complement self-...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.10.15.21265038v1 on medRxiv