{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:15:42Z","timestamp":1782836142155,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Long COVID is a debilitating condition that lasts for more than three months post-infection by SARS\u2013CoV\u20132. On average, one in ten individuals infected with SARS CoV- 2 develops Long COVID worldwide. A knowledge gap exists in our understanding of the mechanisms, genetic risk factors, and biomarkers that could be associated with Long COVID.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this pilot study we used RNA-Seq to quantify the transcriptomes of peripheral blood mononuclear cells isolated from COVID-recovered individuals, seven with and seven without Long COVID symptoms (age- and sex-matched individuals), on average 6 months after infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventy genes were identified as significantly up- or down-regulated in Long COVID samples, and the vast majority were downregulated. The most significantly up- or downregulated genes fell into two main categories, either associated with cell survival or with inflammation. This included genes such as <jats:italic>ICOS<\/jats:italic> (FDR p = 0.024) and <jats:italic>S1PR1<\/jats:italic> (FDR p = 0.019) that were both up-regulated, indicating that a pro-inflammatory state is sustained in Long COVID PBMCs compared with COVID recovered PBMCs. Functional enrichment analysis identified that immune-related functions were expectedly predominant among the up- or down-regulated genes. The most frequently downregulated genes in significantly altered functional categories were two leukocyte immunoglobulin like receptors <jats:italic>LILRB1<\/jats:italic> (FDR p = 0.005) and <jats:italic>LILRB2<\/jats:italic> (FDR p = 0.027). PCA analysis demonstrated that <jats:italic>LILRB1<\/jats:italic> and <jats:italic>LILRB2<\/jats:italic> expression discriminated all of the Long COVID samples from COVID recovered samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Downregulation of these inhibitory receptors similarly indicates a sustained pro-inflammatory state in Long COVID PBMCs. <jats:italic>LILRB1<\/jats:italic> and <jats:italic>LILRB2<\/jats:italic> should be validated as prospective biomarkers of Long COVID in larger cohorts, over time and against clinically overlapping conditions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1450853","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T06:33:12Z","timestamp":1733207592000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["A blood-based mRNA signature distinguishes people with Long COVID from recovered 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