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However, the reason for this co-occurrence of primary infection and reactivation of latent viruses remains elusive. During the first wave of COVID-19, we assessed all major immune cell populations by flow cytometry in a cohort of 61 patients with moderate to critical COVID-19 at the time of hospitalization. Additional blood samples from these patients were biobanked for later analysis. Using these biobanked samples, we evaluated the co-occurrence of CMV, EBV, as well as HHV-6A and -6B by qPCR. EBV was found to be reactivated not only in patients with critical or severe COVID-19 (24\/33 patients; 72.72%), but also in patients with moderate COVID-19 disease (19\/28; 67.86%) at the time of hospital admission. In contrast, HHV-6A was not detected among any patients, whereas CMV and HHV-6B only occurred in low frewuencies (7.1\u201312.1% and 10.7\u201315.2%, respectively). In COVID-19 patients with EBV reactivation, the degree of expression of the T-cell co-stimulatory CD28 and co-expression of CD28 and the integrin CD11a was diminished on CD8 T-cells. In contrast, the frequency of CD8 T-cells expressing the proliferative exhaustion marker CD57 increased. Collectively, these data point to an altered activation phenotype of circulating CD8 T cells and that higher replicative senescence is associated with EBV reactivation. The data presented here suggests an alteration in the CD8 T-cell compartment with impaired ability to control the EBV reactivation in COVID patients.<\/jats:p>","DOI":"10.1007\/s00430-026-00873-3","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T02:00:52Z","timestamp":1776650452000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acute COVID-19 is associated with altered CD8 T-cells indicative of impaired ability to control Epstein\u2013Barr virus 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