Immunocytometric analysis of COVID patients: A contribution to personalized therapy?

Abstract

Aims: This study aims to cast light on immunocytometric alterations in COVID-19, a potentially fatal viral infection with heterogeneous clinical expression and a not completely defined pathophysiology.

Methods: We studied 35 COVID patients at hospital admission testing by cytofluorimetry a large panel of lymphocyte subpopulations and serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-17A and the soluble receptor of IL-17A (IL-17RA).

Key findings: At hospital admission, total lymphocytes and most T and B subpopulations were reduced in 50-80% of patients, with close relationship to disease severity. While activated T helper 1 (TH1) and TH17 cells resulted normal or higher. Serum IL-6 was increased in all patients, while TNF-α and IL-17A were higher in advanced stages. A patient subset with low severity had very high IL-17RA levels. Tocilizumab treatment caused an increase of IL-17A in 3/6 patients and a reduction in 3 others, while the lymphocyte number increased in 3 patients and did not change in the others.

Significance: Cytofluorimetry revealed a functional exhaustion of most lymphocyte populations in COVID patients not involving activated TH1 and TH17. Consequently, there was a relevant cytokines production that contributes to impair the respiratory inflammation. The increase of TH17 and IL-17 in a subset of cases and the evidence of a significant increase of IL-17RA (that prevents the interaction of IL-17 with the cell receptor) in patients with low severity suggest that some patients could benefit from monoclonal antibodies treatment targeting IL-17 pathway. Immunocytofluorimetric markers may contribute to a personalized therapy in COVID patients.

Keywords: COVID-19; Lymphocyte subpopulations; SARS-CoV-2; Serum cytokines.

Fig. 1

Serum levels (pg/mL) of TNF-α, interleukin-6, interleukin-17A and interleukin-17 RA in 35 COVID patients at hospital admission. Gray areas indicate the reference ranges.

Fig. 2

Total, T, B and NK lymphocytes (N/mmc) in 35 COVID patients at hospital admission. Gray areas indicate the reference ranges.

Fig. 3

A) Naïve, activated and memory lymphocytes (N/mmc) in 35 COVID patients at hospital admission. B) Helper, suppressor and helper/suppressor ratio in 35 COVID patients at hospital admission. Gray areas indicate the reference ranges.

Fig. 4

Regulatory, activated, TH17, TH1, activated TH17 and activated TH1 lymphocytes (N/mmc) in 35 COVID patients at hospital admission. Gray areas indicate the reference ranges.