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Methods of Pediatric Post-COVID Condition Studies in High-Impact Journals: A Systematic Review
Mary Rozelle1, Alyson Haslam1,2, Vinay Prasad1,3,4
1Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
Insights
Rigorous study designs are crucial for defining pediatric post-COVID condition. Using test-negative controls and standardized reporting improves accuracy in understanding long-term health effects in children and adolescents.
Area of Science:
- Pediatric Health
- Infectious Diseases
- Epidemiology
Background:
- Diagnosing post-COVID condition in children is complicated by pre-existing health issues.
- Lack of standardized clinical phenotypes hinders definition and epidemiological estimates.
- High-impact studies on pediatric post-COVID condition are scarce, limiting policy-informing evidence.
Purpose of the Study:
- To review and assess the methodology of studies on post-COVID condition in pediatric populations.
- To evaluate highly cited studies for their visibility and potential to inform policy.
- To characterize the methods used in examining post-COVID condition in children and adolescents.
Main Methods:
- Searched PubMed and Web of Science for highly cited pediatric studies on post-COVID condition up to July 2024.
- Included observational or risk-benefit studies from journals with an impact factor ≥5.
- Assessed risk of bias using Joanna Briggs Institute and ROBINS-I tools, classifying studies by control group type (test-negative vs. non-test-negative).
Main Results:
- Analyzed 24 of 426 publications; 38% used test-negative controls, 63% did not.
- Prospective cohort designs were more common in test-negative studies (44%) than non-test-negative studies (33%).
- Incomplete demographic reporting (sex, psychiatric history, comorbidities, BMI) was frequent, with small sample sizes.
Conclusions:
- Highlights the need for rigorous study designs to minimize bias and confounding in pediatric post-COVID condition research.
- Emphasizes the importance of test-negative matched controls for accurate risk factor assessment.
- Recommends standardizing demographic reporting to enhance comparability and consistency in pediatric post-COVID condition studies.
Importance:
Preexisting health conditions complicate post-COVID condition diagnosis in children and adolescents, while the lack of standardized clinical phenotypes challenges its definition and epidemiological estimates. Prospective studies with robust methodologies are needed to minimize bias and confounders, yet they remain scarce in high-impact factor journals.
Objective:
To review, characterize, and assess the methodology used in studies examining post-COVID condition in children and pediatric populations in highly cited studies, which have greater visibility and are likely to be used in informing policy.
Evidence Review:
Studies on PubMed and studies with high citations on Web of Science published through July 2024 were reviewed. Pediatric studies from journals with an impact factor of 5 or higher were included if they employed observational or risk-benefit designs. Studies were classified based on whether they included a SARS-CoV-2 test-negative control group or a non-test-negative group, which included studies with either no comparator or a different type of comparator. Joanna Briggs Institute and Risk of Bias in Nonrandomized Studies of Exposures tools assessed the risk of bias.
Findings:
Of 426 publications, 24 were analyzed; 9 studies (38%) used test-negative controls, while 15 studies (63%) did not (P < .001). Among studies with test-negative groups, 4 (44%) used prospective cohort designs vs 5 (33%) studies without a test-negative group. Demographic reporting of post-COVID condition cases varied. Sex was reported in 12 studies (50%), but the median (IQR) sample size was small (27 female patients [14-110]; 21 male patients [10-79]). Psychiatric history was often not reported (20 patients [83%]), as well as a lack of history of comorbidities (16 patients [67%]) or body mass index (15 patients [63%]). Among 9 test-negative control studies, 4 (44%) used matched control design, while only 1 (11%) accounted for confounders by sex-stratifying results.
Conclusions And Relevance:
These findings highlight the need for rigorous study designs that minimize bias and confounding, ensuring a clearer definition of pediatric post-COVID condition and its sequelae. Employing true test-negative matched controls is essential for distinguishing common symptoms and assessing risk factors, while standardizing demographic reporting strengthens comparability and ensures consistency in patient selection.
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