Frontiers in Immunology (Sep 2023)

COVID-19 patients display changes in lymphocyte subsets with a higher frequency of dysfunctional CD8lo T cells associated with disease severity

  • Luisina Ines Onofrio,
  • Luisina Ines Onofrio,
  • Constanza Marin,
  • Constanza Marin,
  • Jeremías Dutto,
  • Jeremías Dutto,
  • María Belén Brugo,
  • María Belén Brugo,
  • Ruth Eliana Baigorri,
  • Ruth Eliana Baigorri,
  • Sabrina Noemi Bossio,
  • Sabrina Noemi Bossio,
  • Juan Nahuel Quiróz,
  • Juan Nahuel Quiróz,
  • Laura Almada,
  • Laura Almada,
  • Federico Ruiz Moreno,
  • Federico Ruiz Moreno,
  • Carolina Olivera,
  • Carolina Olivera,
  • Silene M. Silvera-Ruiz,
  • Silene M. Silvera-Ruiz,
  • Nicolás Eric Ponce,
  • Nicolás Eric Ponce,
  • Paula Alejandra Icely,
  • Paula Alejandra Icely,
  • María Carolina Amezcua Vesely,
  • María Carolina Amezcua Vesely,
  • Laura Fozzatti,
  • Laura Fozzatti,
  • María Cecilia Rodríguez-Galán,
  • María Cecilia Rodríguez-Galán,
  • Cinthia Carolina Stempin,
  • Cinthia Carolina Stempin,
  • Laura Cervi,
  • Laura Cervi,
  • ImmunoCovid-CBA,
  • Belkys Angélica Maletto,
  • Belkys Angélica Maletto,
  • Eva Virginia Acosta Rodríguez,
  • Eva Virginia Acosta Rodríguez,
  • Mariana Bertone,
  • Claudio Daniel Abiega,
  • Daiana Escudero,
  • Adrián Kahn,
  • Juan Pablo Caeiro,
  • Mariana Maccioni,
  • Mariana Maccioni,
  • Claudia Cristina Motrán,
  • Claudia Cristina Motrán,
  • Adriana Gruppi,
  • Adriana Gruppi,
  • Claudia Elena Sotomayor,
  • Claudia Elena Sotomayor,
  • Laura Silvina Chiapello,
  • Laura Silvina Chiapello,
  • Carolina Lucia Montes,
  • Carolina Lucia Montes,
  • Fabio Cerban,
  • Pablo Iribarren,
  • Daniela Soledad Arroyo,
  • Gabriel Moron

DOI
https://doi.org/10.3389/fimmu.2023.1223730
Journal volume & issue
Vol. 14

Abstract

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This work examines cellular immunity against SARS-CoV-2 in patients from Córdoba, Argentina, during two major waves characterized by different circulating viral variants and different social behavior. Using flow cytometry, we evaluated the main lymphocyte populations of peripheral blood from hospitalized patients with moderate and severe COVID-19 disease. Our results show disturbances in the cellular immune compartment, as previously reported in different cohorts worldwide. We observed an increased frequency of B cells and a significant decrease in the frequency of CD3+ T cells in COVID-19 patients compared to healthy donors (HD). We also found a reduction in Tregs, which was more pronounced in severe patients. During the first wave, the frequency of GZMB, CD107a, CD39, and PD-1-expressing conventional CD4+ T (T conv) cells was significantly higher in moderate and severe patients than in HD. During the second wave, only the GZMB+ T conv cells of moderate and severe patients increased significantly. In addition, these patients showed a decreased frequency in IL-2-producing T conv cells. Interestingly, we identified two subsets of circulating CD8+ T cells with low and high CD8 surface expression in both HD and COVID-19 patients. While the percentages of CD8hi and CD8lo T cells within the CD8+ population in HD are similar, a significant increase was observed in CD8lo T cell frequency in COVID-19 patients. CD8lo T cell populations from HD as well as from SARS-CoV-2 infected patients exhibited lower frequencies of the effector cytokine-producing cells, TNF, IL-2, and IFN-γ, than CD8hi T cells. Interestingly, the frequency of CD8lo T cells increased with disease severity, suggesting that this parameter could be a potential marker for disease progression. Indeed, the CD8hi/CD8lo index helped to significantly improve the patient’s clinical stratification and disease outcome prediction. Our data support the addition of, at least, a CD8hi/CD8lo index into the panel of biomarkers commonly used in clinical labs, since its determination may be a useful tool with impact on the therapeutic management of the patients.

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