1. 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.
- Author
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Mortaz, Esmaeil, Jamaati, Hamidreza, Dezfuli, Neda K., Sheikhzade, Hakime, Hashemian, Seyed MohammadReza, Roofchayee, Neda Dalil, Dastan, Frazaneh, Tabarsi, Payam, Folkerts, Gert, Garssen, Johan, Mumby, Sharon, and Adcock, Ian M.
- Subjects
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COVID-19 , *LOPINAVIR-ritonavir , *LYMPHOCYTES , *T-cell exhaustion , *REMDESIVIR - 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 (CTLA4) 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 CTLA4 + 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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