Long-term manifestations and modifiers of prevalence estimates of the post-COVID-19 syndrome: A systematic review and meta-analysis

  1. Daniel De-la-Rosa-Martinez
  2. Marco Antonio Delaye-Martínez
  3. Omar Yaxmehen Bello-Chavolla
  4. Alejandro Sicilia-Andrade
  5. Isaac David Juárez-Cruz
  6. Carlos A. Fermín-Martínez
  7. Alejandro Márquez-Salinas
  8. Enrique Cañedo-Guerra
  9. Luisa Fernández-Chirino
  10. Mónica Martínez-Gutiérrez
  11. Daniel Eduardo Sandoval-Colin
  12. Diana Vilar-Compte

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Abstract

Background

Post-acute COVID-19 syndrome (PACS) is a multi-system disease comprising persistent symptomatology after the acute phase of infection. Long-term PACS effects significantly impact patient outcomes, but their incidence remains uncharacterized due to high heterogeneity between studies. Therefore, we aimed to summarize published data on PACS, characterizing the clinical presentation, prevalence, and modifiers of prevalence estimates.

Method

In this systematic review and meta-analysis, we research MEDLINE for original studies published from January 1st, 2020, to January 31st, 2021, that reported proportions of PACS manifestations. Studies were eligible for inclusion if they included patients aged ≥18 years with confirmed COVID-19 by RT-PCR or antigen testing and a minimum follow-up of 21 days. The prevalence of individual manifestations across studies was pooled using random-effects meta-analysis. For evaluating determinants of heterogeneity, meta-regression analysis was performed. This study was registered in PROSPERO (CRD42019125025).

Results

After screening 1,235 studies, we included 29 reports for analysis. Twenty-seven meta-analyses were performed, and 61 long-term manifestations were described. The pooled prevalence of PACS was 56% (95%CI 45-66%), with the most common manifestations being diminished health status, fatigue, asthenia, dyspnea, myalgias, hyposmia and dysgeusia. Most of the included studies presented high heterogeneity. After conducting the meta-regression analysis, we identified that age, gender, number of comorbidities, and reported symptoms significantly modify the prevalence estimation of PACS long-term manifestations.

Conclusion

PACS is inconsistently reported between studies, and population characteristics influence the prevalence estimates due to high heterogeneity. A systematized approach for the study of PACS is needed to characterize its impact adequately.

Funding

none

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  1. ScreenIT

    SciScore for 10.1101/2021.10.17.21265123: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search criteria: A sensitive reference search was conducted using MEDLINE (via PubMed) to include manuscripts from January 1st, 2020, to January 31st, 2021.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    A preliminary search was made in PubMed, looking for relevant studies reporting the clinical status of patients recovered from COVID-19 several weeks after the acute illness.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)

    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:
    Until now, there is no specific treatment or management to treat PACS manifestations; however, recent data on the impact of COVID-19 vaccinations on symptom recovery in PACS is promising and may provide a viable pathway to reduce its burden despite the emergence of new SARS-CoV-2 variants or breakthrough infections [55–57] Our study has several limitations. Available data were primarily extracted from observational studies with no standardized symptoms in MEDLINE. Also, post-acute COVID-19 syndrome definitions were not available, contributing to increased risks of bias. Results should be interpreted with caution as high expected heterogeneity was found in most meta-analytic results. Despite that, a strength of our study was the meta-regression analysis conducted to explore for modifiers of prevalence estimates for post-acute COVID-19 syndrome. In addition, our findings are similar to those previously reported. Comorbidities were not available for eight manuscripts for meta-regression analysis, and one article did not specify the proportion of women in the population. Our findings may help standardize populations to study PACS after acute COVID-19 in future studies and to provide better estimates of long-term manifestations, influencing PACS-related public policy. Longitudinal studies on incident COVID-19 cases require standardized approaches regarding the definition of PACS and long-term manifestations, consistent follow-up times across studies and populations with diverse cl...

    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.

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  2. Version published to 10.1101/2021.10.17.21265123 on medRxiv