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The control gap in long COVID research: a meta-epidemiological analysis

Panagiotopoulos, A.-P.; Laskaris, A.; Tsakri, D.; Manoussopoulos, Y.; Anastassopoulou, C.; Tsakris, A.; Ioannidis, J.

2026-05-21 epidemiology
10.64898/2026.05.16.26353381 medRxiv
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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. Design Cross-sectional meta-epidemiological evaluation of published post-acute COVID-19 prevalence studies, supplemented by a corresponding-author survey. Setting Published studies identified through a systematic review by Hou et al. (2025) and supplementary data obtained through direct email contact with corresponding authors. Participants A total of 440 published long COVID prevalence studies. Main Outcome measures Presence and type of comparator group, reliance on solely self-reported outcomes, acknowledgment of lack of a control group among uncontrolled studies, and availability of additional comparator data through author survey. Results Among 440 studies, 372 (84.5%) reported no control group on their publication. 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 anywhere in text. Corresponding authors of 140 studies (31.8%) responded to the survey; among them, 126 (90.0%) reported no additional comparative data, while 14 (10.0%) mentioned some available comparative datasets (19 additional datasets). Almost all of that information (10/14, 17/19) had been already published in other articles not captured by the Hou et al. systematic review. 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, underscoring the need for appropriately matched comparators and more objective outcome assessment. Registration The protocol was prospectively registered on the Open Science Framework (https://osf.io/f4hra).

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