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Despite the urgent need for better management strategies, research into long COVID is losing momentum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To help tackle this loss of momentum, this article analyses the major challenges impeding progress and proposes innovative strategies to navigate them and to reinvigorate this research field.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>The analysis of the long COVID research domain drew on a broad range of scientific literature to identify major barriers to research and potential pathways forward.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The research highlighted critical obstacles, including the lack of reliable biomarkers which has necessitated a reliance on symptom reporting that is inherently heterogenous, temporally complex and often confounded by symptoms arising from pre\u2010existing comorbidities. The absence of pre\u2010infection baseline data further complicates the distinction between long COVID\u2010specific pathophysiology and the effects of pre\u2010existing co\u2010morbidities. Additionally, the long COVID patient population has heterogenous multiorgan pathology, and this diversity makes it difficult to identify and interpret clinical findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Addressing these methodological and conceptual challenges is essential to accelerate the understanding of long COVID pathophysiology and guide the development of effective interventions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jep.70180","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T11:38:59Z","timestamp":1755085139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Stagnation to Strategy: Challenges in Advancing Long COVID Research"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3787-7081","authenticated-orcid":false,"given":"Appleby","family":"Ellen","sequence":"first","affiliation":[{"name":"Wadham College University of Oxford  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"Post COVID\u201019 Condition (Long COVID) (June 2025) https:\/\/www.who.int\/europe\/news-room\/fact-sheets\/item\/post-covid-19-condition."},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2022-072529","article-title":"Long Covid Outcomes at One Year After Mild SARS\u2010CoV\u20102 Infection: Nationwide Cohort Study","volume":"380","author":"Mizrahi B.","year":"2023","journal-title":"BMJ"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lana.2025.101026"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01810-6"},{"key":"e_1_2_13_6_1","unstructured":"Self\u2010Reported Coronavirus (COVID\u201019) Infections and Associated Symptoms England and Scotland \u2010 Office for National Statistics (November 2024) https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/healthandsocialcare\/conditionsanddiseases\/articles\/selfreportedcoronaviruscovid19infectionsandassociatedsymptomsenglandandscotland\/november2023tomarch2024#."},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/frma.2023.1149091"},{"key":"e_1_2_13_8_1","first-page":"38","article-title":"Characterizing Long Covid in an International Cohort: 7 Months of Symptoms and Their Impact","author":"Davis H. 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