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However, the underlying cause for the depletion of T-cells in COVID-19 patients remains incompletely understood. In this study, we assessed the presence of different T-cell subsets in the progression of COVID-19 from mild to severe disease,\u00a0with a focus on TCF1 expressing progenitor T-cells\u00a0that are\u00a0needed to replenish peripheral T-cells during infection.\u00a0Our results showed a preferential decline in TCF1+ progenitor CD4 and CD8+\u00a0T-cells with disease severity. This decline was seen in\u00a0various TCF1+ subsets including naive, memory and effector-memory cells, and surprisingly, was accompanied by a loss in cell division as seen by a marked decline in\u00a0Ki67 expression. In addition, TCF1+ T-cells showed a reduction in pro-survival regulator, BcL2, and the appearance of a new population of TCF1 negative caspase-3 expressing cells in peripheral blood from patients with severe disease. The decline in TCF1+ T-cells\u00a0was also\u00a0seen in a subgroup of severe patients with vitamin D deficiency. Lastly, we found that\u00a0sera from severe patients inhibited TCF1 transcription ex vivo which was attenuated by a blocking\u00a0antibody against the cytokine,\u00a0interleukin-12 (IL12). Collectively, our findings underscore the potential\u00a0significance of TCF1+ progenitor T-cells in accounting for\u00a0the loss of immunity in severe COVID-19 and outline\u00a0an array of markers that could be used to identify disease progression.<\/jats:p>","DOI":"10.1038\/s42003-024-05922-2","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T19:02:02Z","timestamp":1714762922000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Decreased progenitor TCF1\u2009+\u2009T-cells correlate with COVID-19 disease severity"],"prefix":"10.1038","volume":"7","author":[{"given":"Thai Hien","family":"Tu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Grunbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Santinon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kazanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-8949","authenticated-orcid":false,"given":"Nicholas","family":"Rozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin","family":"Mihalcioiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5295-9019","authenticated-orcid":false,"given":"Christopher E.","family":"Rudd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"5922_CR1","doi-asserted-by":"publisher","first-page":"e237","DOI":"10.1371\/journal.pmed.0030237","volume":"3","author":"J ter Meulen","year":"2006","unstructured":"ter Meulen, J. et al. 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