<p>Increasing evidence suggests that reactivation of latent EBV in patients with COVID-19 may be linked to the development of post-acute sequelae of COVID-19, colloquially known as Long COVID. 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 (7.1–12.1% and 10.7–15.2%, 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.</p>

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Acute COVID-19 is associated with altered CD8 T-cells indicative of impaired ability to control Epstein–Barr virus reactivation

  • Ulrik Stervbo,
  • Moritz Anft,
  • Krystallenia Paniskaki,
  • Arturo Blazquez-Navarro,
  • Adrian Doevelaar,
  • Sarah Skrzypczyk,
  • Eva Kohut,
  • Julia Kurek,
  • Patrizia Wehler,
  • Sviatlana Kaliszczyk,
  • Kamil Rosiewicz,
  • Felix S. Seibert,
  • Bodo Hölzer,
  • Constantin J. Thieme,
  • Toralf Roch,
  • Margarethe Justine Konik,
  • Marc Moritz Berger,
  • Thorsten Brenner,
  • Uwe Kölsch,
  • Michael Adamzik,
  • Michael Schmueck-Henneresse,
  • Carmen Scheibenbogen,
  • Sebastian Dolff,
  • Ulf Dittmer,
  • Oliver Witzke,
  • Timm H. Westhoff,
  • Nina Babel

摘要

Increasing evidence suggests that reactivation of latent EBV in patients with COVID-19 may be linked to the development of post-acute sequelae of COVID-19, colloquially known as Long COVID. 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 (7.1–12.1% and 10.7–15.2%, 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.