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Comparability of control and comparison groups in studies assessing long COVID

  • Alyson Haslam
    Correspondence
    Corresponding author: Alyson Haslam, PhD, Department of Epidemiology and Biostatistics, UCSF Mission Bay Campus | Mission Hall: Global Health & Clinical Sciences Building | 550 16th St, 2nd Fl, San Francisco, CA, 94158
    Affiliations
    University of California San Francisco, 550 16th St, 2nd Fl, San Francisco, CA, 94158

    Department of Oncology, Geneva University Hospital, 4 Gabrielle-Perret-Gentil St, 1205, Geneva, Switzerland
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  • Vinay Prasad
    Affiliations
    University of California San Francisco, 550 16th St, 2nd Fl, San Francisco, CA, 94158

    Department of Oncology, Geneva University Hospital, 4 Gabrielle-Perret-Gentil St, 1205, Geneva, Switzerland
    Search for articles by this author
Published:January 25, 2023DOI:https://doi.org/10.1016/j.amjmed.2023.01.005

      Abstract

      Background

      Awareness of long COVID began primarily through media and social media sources, which eventually led to the development of various definitions, based on methodologies of varying quality. We sought to characterize comparison groups in long COVID studies and evaluate comparability of the different groups.

      Methods

      We searched Embase, Web of Science, and PubMed for original research articles published in high-impact journals. We included studies on human patients with long COVID outcomes, and we abstracted study-related characteristics, as well as long COVID characteristics.

      Results

      Of the 83 studies, 3 were RCTs testing interventions for long COVID, and 80 (96.4%) were observational studies. Among the 80 observational studies, 76 (95%) were trying to understand the incidence, prevalence, and risk factors for long COVID, two (2.5%) examined prevention strategies, and 2 (2.5%) examined treatment strategies. Among those 80 studies, 45 (56.2%) utilized a control or comparison group and 35 (43.8%) did not. Compared to 95% of observational studies that documented symptoms or assessed risk factors, all randomized studies assessed treatment strategies. We found 48.8% of observational studies did any adjustment for covariates, including demographics or health status. Of those that did adjust for covariates, 15 (38.5%) adjusted for four or fewer variables. We found that 26.5% of all studies and 45.8% of studies with a control/comparator group matched participants on at least one variable.

      Conclusion

      Long COVID studies in high-impact journals primarily examine symptoms and risk factors of long COVID, often lack an adequate comparison group, and often do not control for potential confounders. Our results suggest that standardized definitions for long COVID, which are often based on data from uncontrolled and potentially biased studies, should be reviewed to ensure that they are based on objective data.

      Keywords

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      References

        • Callard F
        • Perego E.
        How and why patients made Long Covid.
        Soc Sci Med. 2021; 268113426https://doi.org/10.1016/j.socscimed.2020.113426
        • Yong E
        Long-Haulers Are Redefining COVID-19.
        The Atlantic, 2020 (August 19Accessed October 19, 2022)
      1. COVID-19 Rapid Guideline: Managing the Long-Term Effects of COVID-19.
        National Institute for Health and Care Excellence (NICE), 2020
        • World Health Organization
        A clinical case definition of post COVID-19 condition by a Delphi consensus.
        2021 (October 6Accessed September 5, 2022)
        • Ceban F
        • Leber A
        • Jawad MY
        • et al.
        Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research.
        Infect Dis (Lond). 2022; 54: 467-477https://doi.org/10.1080/23744235.2022.2043560
        • Giuntella O
        • Hyde K
        • Saccardo S
        • Sadoff S.
        Lifestyle and mental health disruptions during COVID-19.
        Proc Natl Acad Sci USA. 2021; 118https://doi.org/10.1073/pnas.2016632118
        • Brusaferri L
        • Alshelh Z
        • Martins D
        • et al.
        The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic.
        Brain Behav Immun. 2022; 102: 89-97https://doi.org/10.1016/j.bbi.2022.02.018
        • Wisk LE
        • Gottlieb MA
        • Spatz ES
        • et al.
        Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.
        JAMA Netw Open. 2022; 5e2244486https://doi.org/10.1001/jamanetworkopen.2022.44486
        • Cutler DM.
        The Economic Cost of Long COVID: An Update.
        2022 (Published online July)