Long COVID research often lacks controls and does not acknowledge this limitation: meta-epidemiological analysis
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Objectives
To quantify the frequency of baseline control-group use in published long COVID prevalence studies and assess their key methodological features.
Methods
We performed a meta-epidemiological assessment of 440 post-acute COVID-19 prevalence publications from an existing systematic review. To evaluate study design and methodological transparency, we extracted data on the inclusion and classification of comparator groups, the exclusive use of self-reported outcome measures, and whether uncontrolled investigations explicitly recognized the omission of a control group as a limitation. In addition, we surveyed by email the corresponding authors of these articles to determine if any supplementary comparative data existed. The protocol was prospectively registered (DOI: 10.17605/OSF.IO/T2UP9).
Results
Among 440 studies, 372 (84.5%) reported no control group. Healthy or uninfected comparators were reported in 55 studies (12.5%) and other comparator types in 14 (3.2%); 1 study included both categories. Solely self-reported outcomes were used in 279 studies (63.4%). Among 372 uncontrolled studies, 244 (65.6%) did not explicitly acknowledge the absence of a baseline comparator as a limitation. Corresponding authors of 140 studies (31.8%) responded to the survey; 126 (90.0%) reported no additional comparative data, while 14 (10.0%) mentioned some available comparative datasets (19 additional datasets). Almost all that information (10/14, 17/19) had been already published in other articles not captured by the index systematic review. Studies with controls had modestly higher citation impact (median 7 versus 4 per year, p=0.002).
Conclusions
Most published long COVID prevalence studies lacked comparator groups and relied exclusively on self-reported outcomes without acknowledging this limitation. Direct author contact identified little additional comparator information. Much of the long COVID prevalence literature may therefore be poorly suited to estimating burden attributable specifically to SARS-CoV-2.
Key Points
Question
What is the frequency of baseline control group inclusion and the reliance on subjective outcomes in published long COVID prevalence studies?
Findings
This meta-epidemiological analysis demonstrates that over 80% of published long COVID prevalence studies lacked a baseline non-COVID control group. Most of these investigations also relied exclusively on subjective patient-reported outcomes without explicitly acknowledging the absence of a comparator as a limitation.
Meaning
These findings suggest that the majority of the long COVID prevalence literature is poorly suited to accurately estimate the symptom burden specifically attributable to SARS-CoV-2.
