Dataset Information

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.

SUBMITTER: Cacciapuoti S

PROVIDER: S-EPMC7456265 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Cacciapuoti Sara S De Rosa Annunziata A Gelzo Monica M Megna Matteo M Raia Maddalena M Pinchera Biagio B Pontarelli Agostina A Scotto Riccardo R Scala Emanuele E Scarano Francesco F Scalia Giulia G Castaldo Giuseppe G Fabbrocini Gabriella G Gentile Ivan I Parrella Roberto R

Life sciences 20200829

<h4>Aims</h4>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.<h4>Methods</h4>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).<h4>Key findings</h4>At hospital admission ...[more]

PMID: 32871183

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Project description:AimsCoronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Drug therapy is one of the major treatments, but contradictory results of clinical trials have been reported among different individuals. Furthermore, comprehensive analysis of personalized pharmacotherapy is still lacking. In this study, analyses were performed on 47 well-characterized COVID-19 drugs used in the personalized treatment of COVID-19.MethodsClinical trials with published results of drugs use for COVID-19 treatment were collected to evaluate drug efficacy. Drug-to-Drug Interactions (DDIs) were summarized and classified. Functional variations in actionable pharmacogenes were collected and systematically analysed. "Gene Score" and "Drug Score" were defined and calculated to systematically analyse ethnicity-based genetic differences, which are important for the safer use of COVID-19 drugs.ResultsOur results indicated that four antiviral agents (ritonavir, darunavir, daclatasvir and sofosbuvir) and three immune regulators (budesonide, colchicine and prednisone) as well as heparin and enalapril could generate the highest number of DDIs with common concomitantly utilized drugs. Eight drugs (ritonavir, daclatasvir, sofosbuvir, ribavirin, interferon alpha-2b, chloroquine, hydroxychloroquine (HCQ) and ceftriaxone had actionable pharmacogenomics (PGx) biomarkers among all ethnic groups. Fourteen drugs (ritonavir, daclatasvir, prednisone, dexamethasone, ribavirin, HCQ, ceftriaxone, zinc, interferon beta-1a, remdesivir, levofloxacin, lopinavir, human immunoglobulin G and losartan) showed significantly different pharmacogenomic characteristics in relation to the ethnic origin of the patient.ConclusionWe recommend that particularly for patients with comorbidities to avoid serious DDIs, the predictive, preventive, and personalized medicine (PPPM, 3 PM) strategies have to be applied for COVID-19 treatment, and genetic tests should be performed for drugs with actionable pharmacogenes, especially in some ethnic groups with a higher frequency of functional variations, as our analysis showed. We also suggest that drugs associated with higher ethnic genetic differences should be given priority in future pharmacogenetic studies for COVID-19 management. To facilitate translation of our results into clinical practice, an approach conform with PPPM/3 PM principles was suggested. In summary, the proposed PPPM/3 PM attitude should be obligatory considered for the overall COVID-19 management.Supplementary informationThe online version contains supplementary material available at 10.1007/s13167-021-00247-0.

Dataset Information

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

Aims

Methods

Key findings

Significance

Publications

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

Similar Datasets

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