Phenotypic Timeline Kinetics, Integrative Networks, and Performance of T- and B-Cell Subsets Associated with Distinct Clinical Outcome of Severe COVID-19 Patients

The present study aimed to evaluate the kinetics of the phenotypic profile and integrative networks of T/B-cells in severe COVID-19 patients, categorized according to disease outcome, during the circulation of the B.1.1.28 and B.1.1.33 SARS-CoV-2 strains in Brazil. Peripheral blood obtained at distinct time points (baseline/D0; D7; D14-28) was used for ex vivo flow cytometry immunophenotyping. The data demonstrated a decrease at D0 in the frequency of CD3⁺ T-cells and CD4⁺ T-cells and an increase in B-cells with mixed activation/exhaustion profiles. Higher changes in B-cell and CD4⁺ T-cells at D7 were associated with discharge/death outcomes, respectively. Regardless of the lower T/B-cell connectivity at D0, distinct profiles from D7/D14-28 revealed that, while discharge was associated with increasing connectivity for B-cells, CD4⁺ and CD8⁺ T-cells death was related to increased connectivity involving B-cells, but with lower connections mediated by CD4⁺ T-cells. The CD4⁺CD38⁺ and CD8⁺CD69⁺ subsets accurately classified COVID-19 vs. healthy controls throughout the kinetic analysis. Binary logistic regression identified CD4⁺CD107a⁺, CD4⁺T-bet⁺, CD8⁺CD69⁺, and CD8⁺T-bet⁺ at D0 and CD4⁺CD45RO⁺CD27⁺ at D7 as subsets associated with disease outcomes. Results showed that distinct phenotypic timeline kinetics and integrative networks of T/B-cells are associated with COVID-19 outcomes that may subsidize the establishment of applicable biomarkers for clinical/therapeutic monitoring.