SARS-CoV-2-reactive IFN-γ CD4 + and CD8 + T cells, clinical severity biomarkers and mortality in unvaccinated critically ill COVID-19 patients

Abstract Objectives: We examined the relationship between peripheral blood levels of SARS-CoV-2 S1/M-reactive IFN-γ-producing CD4+ and CD8+ T cells, serum levels of biomarkers of clinical severity and mortality in critically ill COVID-19 patients. Methods: Immune responses were monitored in 71 non-consecutive patients (49 male and 22 female; median age, 65 years) by whole-blood flow cytometry (326 specimens). SARS-CoV-2 RNA loads in paired tracheal aspirates [TA] (n=147) were available from 54 patients. Serum levels of interleukin-6, ferritin, D-Dimer, lactose dehydrogenase and C-reactive protein in paired sera were known. Results: SARS-CoV-2 T cells (either CD4+, CD8+ or both) were detectable in 70 patients. SARS-CoV-2 IFN-γ CD4+ T-cell responses were documented more frequently than their CD8+ counterparts (62 vs. 56 patients) and were of greater magnitude overall. Detectable SARS-CoV-2 S1/M-reactive CD8+ and CD4+ T-cell responses were associated with higher SARS-CoV-2 RNA loads in TA. SARS-CoV-2 RNA load in TA decreased over time, irrespective of the dynamics of SARS-CoV-2-reactive CD8+ and CD4+ T cells. Conclusion: Enumeration of peripheral blood levels of SARS-CoV-2-S1/M-reactive IFN-γ CD4+ and CD8+ T cells does not predict viral clearance from the lower respiratory tract or poor clinical outcomes in critically ill COVID-19 patients.