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.

Prognostic Role of Neutrophil to Lymphocyte Ratio in COVID-19 Patients: Still Valid in Patients That Had Started Therapy?

“…We found an increase of NLR values in 49 patients with COVID-19 of the I st wave, with a significant increase of the index in parallel with the WHO disease severity, that depends on the gradual increase of neutrophils and on the gradual decrease of lymphocytes in WHO 5-7 patients (11). These evidences fully agree with previous studies (3), among which that of Qin et al (15) which included more than 400 COVID patients.…”

“…These evidences fully agree with previous studies (3), among which that of Qin et al (15) which included more than 400 COVID patients. On the other hand, the cytokine storm that occurs in patients with severe COVID-19, confirmed by the high serum levels of IL-6 in our patients of the I st wave, contributes to the lymphocyte exhaustion (11). Surprisingly, when we analyzed the NLR in 242 patients with COVID-19 of the II nd wave, we did not observe any difference of the ratio between patients of different WHO stage.…”

“…The diagnosis of COVID-19 was confirmed by molecular analysis (RT-PCR) of the nasopharyngeal swab (11) (13,14). We divided our population study in three subgroups: WHO 3, WHO 4, and WHO 5-7 (including COVID-19 patients with WHO stage from 5 to 7).…”

Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset

“…The Th1 deficiency would lead to a decrease in the number of active CTLs and therefore a poor immune response to the viral infection. Other studies, some published during the evaluation of our work, show similar findings (29)(30)(31). However, these studies are based on fewer cases and focus on IFN-g-producing cells, or naïve/effectormemory cells.…”

The Role of Immunogenetics in COVID-19

“…Thus, immunosenescence represents a further potential contributor to the insurgence of fatal complications in COVID-19 [ 8 , 62 , 63 ]. Lymphopenia and accumulation of immune cells showing immunophenotypic and functional signs of exhaustion were commonly documented in COVID-19 patients, correlating with age and severity [ 43 , 68 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. This strong resemblance to immunosenescence makes COVID-19 a possible scenario to deepen the knowledge about the molecular basis affecting normal immune cell metabolism/lifespan/turnover and to determine the importance of genetic variants and epigenetic modifications behind the appearance of inflammaging and immunosenescence [ 66 , 85 , 86 , 87 , 88 ].…”