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

ONOFRIO, LUISINA INES; MARIN, CONSTANZA; DUTTO, JEREMÍAS; BRUGO, MARÍA BELÉN; BAIGORRI, RUTH ELIANA; BOSSIO, SABRINA NOEMI; QUIRÓZ, JUAN NAHUEL; ALMADA, LAURA; RUIZ MORENO, FEDERICO; OLIVERA, CAROLINA; SILVERA-RUIZ, SILENE M.; PONCE, NICOLÁS ERIC; ICELY, PAULA ALEJANDRA; AMEZCUA VESELY, MARÍA CAROLINA; FOZZATTI, LAURA; RODRÍGUEZ-GALÁN, MARÍA CECILIA; STEMPIN, CINTHIA CAROLINA; CERVI, LAURA; MALETTO, BELKYS ANGÉLICA; ACOSTA RODRÍGUEZ, EVA VIRGINIA; BERTONE, MARIANA; ABIEGA, CLAUDIO DANIEL; ESCUDERO, DAIANA; KAHN, ADRIÁN; CAEIRO, JUAN PABLO; MACCIONI, MARIANA; MOTRÁN, CLAUDIA CRISTINA; GRUPPI, ADRIANA; SOTOMAYOR, CLAUDIA ELENA; CHIAPELLO, LAURA SILVINA; MONTES, CAROLINA LUCIA; CERBAN, FABIO; IRIBARREN, PABLO; MORON, GABRIEL; ARROYO, DANIELA

Frontiers in Immunology

Frontiers Media

Año: 2023 vol. 14

This work examines cellular immunity against SARS-CoV-2 in patients fromCórdoba, Argentina, during two major waves characterized by differentcirculating viral variants and different social behavior. Using flow cytometry, weevaluated the main lymphocyte populations of peripheral blood fromhospitalized patients with moderate and severe COVID-19 disease. Our resultsshow disturbances in the cellular immune compartment, as previously reportedin different cohorts worldwide. We observed an increased frequency of B cellsand a significant decrease in the frequency of CD3+ T cells in COVID-19 patientscompared to healthy donors (HD). We also found a reduction in Tregs, which wasmore pronounced in severe patients. During the first wave, the frequency ofGZMB, CD107a, CD39, and PD-1-expressing conventional CD4+ T (T conv) cellswas significantly higher in moderate and severe patients than in HD. During thesecond wave, only the GZMB+ T conv cells of moderate and severe patientsincreased significantly. In addition, these patients showed a decreased frequencyin IL-2-producing T conv cells. Interestingly, we identified two subsets ofcirculating CD8+ T cells with low and high CD8 surface expression in both HDand COVID-19 patients. While the percentages of CD8hi and CD8lo T cells withinthe CD8+ population in HD are similar, a significant increase was observed inCD8lo T cell frequency in COVID-19 patients. CD8lo T cell populations from HDas well as from SARS-CoV-2 infected patients exhibited lower frequencies of theeffector cytokine-producing cells, TNF, IL-2, and IFN-g, 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 diseaseprogression. Indeed, the CD8hi/CD8lo index helped to significantly improve thepatient’s clinical stratification and disease outcome prediction. Our data supportthe addition of, at least, a CD8hi/CD8lo index into the panel of biomarkerscommonly used in clinical labs, since its determination may be a useful toolwith impact on the therapeutic management of the patients.