T-Helper Cell Subset Response Is a Determining Factor in COVID-19 Progression

Abstract

The immune response type organized against viral infection is determinant in the prognosis of some infections. This work has aimed to study Th polarization in acute COVID-19 and its possible association with the outcome through an observational prospective study. Fifty-eight COVID-19 patients were recruited in the Medicine Department of the hospital "12 de Octubre," 55 patients remaining after losses to follow-up. Four groups were established according to maximum degree of disease progression. T-helper cell percentages and phenotypes, analyzed by flow cytometer, and serum cytokines levels, analyzed by Luminex, were evaluated when the microbiological diagnosis (acute phase) of the disease was obtained. Our study found a significant reduction of %Th1 and %Th17 cells with higher activated %Th2 cells in the COVID-19 patients compared with reference population. A higher percent of senescent Th2 cells was found in the patients who died than in those who survived. Senescent Th2 cell percentage was an independent risk factor for death (OR: 13.88) accompanied by the numbers of total lymphocytes (OR: 0.15) with an AUC of 0.879. COVID-19 patients showed a profile of pro-inflammatory serum cytokines compared to controls, with higher levels of IL-2, IL-6, IL-15, and IP-10. IL-10 and IL-13 were also elevated in patients compared to controls. Patients who did not survive presented significantly higher levels of IL-15 than those who recovered. No significant differences were observed according to disease progression groups. The study has shown that increased levels of IL-15 and a high Th2 response are associated with a fatal outcome of the disease.

Keywords: COVID-19; SARS-Cov2; T-helper; cytokines; immunity.

Figure 1

Patient classification according to the most critical event during hospitalization. (A) G1-Hospitalized patients who died. (B) G2-Alive patients who ended up in ICU. (C) G3-Hospitalized patients with poor prognosis characteristics who needed immunomodulatory treatment. (D) G4-Hospitalized patients with mild symptoms who did not need immunomodulatory treatment.

Figure 2

Th distribution in COVID-19 patients according to the most critical event during disease. A–C) Total proportion of Th 1 (A). Th17 (B) and Th2 (C). (D, F) Proportion of quiescent Th1 (D), Th17 (E) and Th2 (F). (G–I) Proportion of early activated Th1 (G). Th17 (H) and Th2 (I). (J–L) Proportion of late activated Th1 (J), Th17 (K), and Th2 (L). (M–O) Proportion of senescent Th1 (M), Th17 (N), and Th2 (O). G1: Death; G2: Intensive Care Unit; G3: Immunomodulators; G4: Benign-Course. *. <0.05 **. <0.01 ns, not significant.