Evolution of Coronavirus Disease 2019 (COVID-19) Symptoms During the First 12 Months After Illness Onset

  1. Elke Wynberg
  2. Hugo D G van Willigen
  3. Maartje Dijkstra
  4. Anders Boyd
  5. Neeltje A Kootstra
  6. Joost G van den Aardweg
  7. Marit J van Gils
  8. Amy Matser
  9. Marije R de Wit
  10. Tjalling Leenstra
  11. Godelieve de Bree
  12. Menno D de Jong
  13. Maria Prins
  14. RECoVERED Study Group
  15. Ivette Agard
  16. Jane Ayal
  17. Floor Cavdar
  18. Marianne Craanen
  19. Udi Davidovich
  20. Annemarieke Deuring
  21. Annelies van Dijk
  22. Ertan Ersan
  23. Laura del Grande
  24. Joost Hartman
  25. Nelleke Koedoot
  26. Romy Lebbink
  27. Dominique Loomans
  28. Agata Makowska
  29. Tom du Maine
  30. Ilja de Man
  31. Lizenka van der Meij
  32. Marleen van Polanen
  33. Maria Oud
  34. Clark Reid
  35. Leeann Storey
  36. Marc van Wijk

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Abstract

Background

Few robust longitudinal data on long-term coronavirus disease 2019 (COVID-19) symptoms are available. We evaluated symptom onset, severity and recovery across the full spectrum of disease severity, up to one year after illness onset.

Methods

The RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged ≥18 years were enrolled following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis via the local public health service and from hospitals. Standardized symptom questionnaires were completed at enrollment, 1 week and month later, and monthly thereafter. Clinical severity was defined according to World Health Organization (WHO) criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models.

Results

Between 11 May 2020 and 1 May 2021, 342 COVID-19 patients (192 [56%] male) were enrolled, of whom 99/342 (29%) had mild, 145/342 (42%) moderate, 56/342 (16%) severe, and 42/342 (12%) critical disease. The proportion of participants who reported at least 1 persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7% [95% confidence interval {CI} = 76.5–92.7%]) compared to those with mild or moderate disease (30.7% [95% CI = 21.1–40.9%] and 63.8% [95% CI = 54.8–71.5%], respectively). At 12 months after illness onset, two-fifths of participants (40.7% [95% CI = 34.2–7.1]) continued to report ≥1 symptom. Recovery was slower in female compared to male participants (adjusted hazard ratio [aHR] 0.65 [95% CI = .47–.92]) and those with a body mass index [BMI]  ≥30kg/m2 compared to BMI <25kg/m2 (hazard ratio [HR] 0.62 [95% CI = .39–.97]).

Conclusions

COVID-19 symptoms persisted for one year after illness onset, even in some individuals with mild disease. Female sex and obesity were the most important determinants of speed of recovery from symptoms.

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  1. Version published to 10.1093/cid/ciab759
  2. ScreenIT

    SciScore for 10.1101/2021.05.05.21256710: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The RECoVERED study was approved by the medical ethical review board of the Amsterdam University Medical Centre (NL73759.018.20).
    Consent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using Stata (StataCorp LLC, v.15.1) and R (RStudio, v.1.2.5033).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)
    RStudio
    suggested: (RStudio, RRID:SCR_000432)

    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:
    Several limitations must be recognised. Survival bias among the retrospectively-enrolled hospitalised participants may have caused an underestimation of time to complete recovery in those with severe/critical disease, although results were comparable when restricting our analyses to prospectively identified participants. Questionnaires in languages other than Dutch and English were not offered, therefore individuals with a migration background, who have been disproportionally affected by COVID-19, also in Amsterdam[25, 26], were underrepresented in this cohort. Furthermore, misclassification bias may have resulted from using ICU admission as a proxy for critical disease; suitability for ICU admission is also judged by the patient’s chance of survival; indeed, those with critical disease tended to be younger and have a lower BMI than those in the severe group. Finally, the natural progression of disease may differ between SARS-CoV-2 variants[27] and treatments received. Therefore, our results may not be representative for future patients infected with SARS-CoV-2, especially as the treatment landscape for COVID-19 changes and new variants continue to arise. We demonstrated that post-COVID syndrome is common, even after mild disease. Symptoms persisted for nine months after illness onset in one-fifth of participants with mild disease and in more than half of participants with moderate and severe/critical disease. Obesity was the most important predictor of slow recovery and thus...

    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

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  3. Version published to 10.1101/2021.05.05.21256710v1 on medRxiv