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Despite the widespread prevalence, Long-COVID aetiology remains poorly understood, but emerging evidence points to immune dysregulation as a potential mechanism involved in its development or persistence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study presents a unique analysis of the peripheral blood mononuclear cell transcriptomic profile of COVID-19 and Long-COVID patients at single-cell resolution. We reconstructed the cell state and intercellular communication using differentially expressed gene profiling and ligand\u2013receptor interaction analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results reveal altered T and natural killer cell subset proportions, diminished proliferating lymphocyte and B cell signalling capacity, and the expression of exhaustion and cytotoxicity associated genes 1.5\u20132\u2009years post-infection, suggesting incomplete immune recovery. Distinct interferon responses in these cell populations at the acute phase for patients who go on to develop Long-COVID indicate early disease mediator potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, these findings provide insight into the immune processes underlying the progression of COVID-19 into a chronic Long-COVID state. The observed changes in immune cell subsets at the acute phase of the infection may be predictive of Long-COVID progression and could be useful in understanding disease aetiology while the observed long-term effects are crucial to developing therapeutic and diagnostic tools.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08081-6","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:15:10Z","timestamp":1775884510000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immune dysregulation in prolonged Long-COVID: lymphocytes emerge as key mediators of persistent inflammation, exhaustion and cytotoxicity"],"prefix":"10.1186","volume":"24","author":[{"given":"Marta Liva","family":"Springe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krist\u012bne","family":"Vaivode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rihards","family":"Saksis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nine\u013ca Miriama","family":"Vain\u0161e\u013cbauma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ansone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monta","family":"Br\u012bv\u012bba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helvijs","family":"Niedra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vita","family":"Rovite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"key":"8081_CR1","unstructured":"World Health Organisation. 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