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This systematic review (PROSPERO: CRD42024499281) aimed to explore the pathophysiological mechanisms underlying LC and potential treatable traits across symptom\u2010based phenotypes. We included studies with primary data, written in English, focusing on omics analyses of human samples from LC patients with persistent symptoms of at least 3\u2009months. Our search in PubMed and Embase, conducted on January 8, 2024, identified 642 studies, of which 29 met the inclusion criteria after full\u2010text assessment. The risk of bias was evaluated using the Joanna Briggs Institute appraisal tool. The synthesis of omics data, including genomics, transcriptomics, proteomics, metabolomics, and metagenomics, revealed common findings associated with fatigue, cardiovascular, pulmonary, neurological, and gastrointestinal phenotypes. Key findings included mitochondrial dysfunction, dysregulated microRNAs associated with pulmonary dysfunction, tissue impairment, blood\u2013brain barrier disruption, coagulopathy, vascular dysfunction, microbiome disturbances, microbial\u2010derived metabolite production and persistent inflammation. Limitations include cross\u2010study heterogeneity and variability in sampling methods. Our review emphasizes the complexity of LC and the need for further longitudinal omics\u2010integrated studies to advance the development of biomarkers and targeted treatments.<\/jats:p>","DOI":"10.1111\/all.16526","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T09:20:43Z","timestamp":1741944043000},"page":"932-948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Omics Landscape of Long\n                    <scp>COVID<\/scp>\n                    \u2014A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-7760","authenticated-orcid":false,"given":"Nadia","family":"Baalbaki","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine Amsterdam UMC  Amsterdam the Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity  Amsterdam the Netherlands"},{"name":"Amsterdam Public Health  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-7825","authenticated-orcid":false,"given":"Elise M. 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