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

Covid-19, caused by sars-cov-2, requires new approaches to control the disease. programmed cell death protein (pd-1) and cytotoxic t-lymphocyte2013;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,a0;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.