Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study

Esmaeil Mortaz, Hamidreza Jamaati, Neda K Dezfuli, Hakime Sheikhzade, Seyed MohammadReza Hashemian, Neda Dalil Roofchayee, Frazaneh Dastan, Payam Tabarsi, Gert Folkerts, Johan Garssen, Sharon Mumby, Ian M Adcock

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Original languageEnglish
Pages (from-to)99-109
Number of pages11
JournalIranian Journal of Allergy, Asthma and Immunology
Volume22
Issue number1
DOIs
Publication statusPublished - 1 Feb 2023

Bibliographical note

Funding Information:
The authors wish to thank all the study participants.

Publisher Copyright:
Copyright © 2023 Mortaz et al. Published by Tehran University of Medical Sciences.

Keywords

  • Antiviral therapy
  • COVID-19
  • Cytokine storm
  • Cytotoxic T-lymphocyte–associated protein 4
  • Program cell death 1
  • T cells

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