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Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia.

ABSTRACT: The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients' T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1+CD57+ exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4+ T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-?, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.

SUBMITTER: De Biasi S

PROVIDER: S-EPMC7338513 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia.

De Biasi Sara S Meschiari Marianna M Gibellini Lara L Bellinazzi Caterina C Borella Rebecca R Fidanza Lucia L Gozzi Licia L Iannone Anna A Lo Tartaro Domenico D Mattioli Marco M Paolini Annamaria A Menozzi Marianna M Milić Jovana J Franceschi Giacomo G Fantini Riccardo R Tonelli Roberto R Sita Marco M Sarti Mario M Trenti Tommaso T Brugioni Lucio L Cicchetti Luca L Facchinetti Fabio F Pietrangelo Antonello A Clini Enrico E Girardis Massimo M Guaraldi Giovanni G Mussini Cristina C Cossarizza Andrea A

Nature communications 20200706 1

The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients' T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1<sup>+</sup>CD57<sup>+</sup> exhausted T cells. Significant ...[more]

PMID: 32632085

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Project description:BackgroundThe COVID-19 pandemic has caused the relocation of huge financial resources to departments dedicated to infected patients, at the expense of those suffering from other pathologies.AimTo compare clinical features and outcomes in COVID-19 pneumonia and non-COVID-19 pneumonia patients.Patients and methods53 patients (35 males, mean age 61.5 years) with COVID-19 pneumonia and 50 patients (32 males, mean age 72.7 years) with non-COVID-19 pneumonia, consecutively admitted between March and May 2020 were included. Clinical, laboratory and radiological data at admission were analyzed. Duration of hospitalization and mortality rates were evaluated.ResultsAmong the non-COVID patients, mean age, presence of comorbidities (neurological diseases, chronic kidney disease and chronic obstructive pulmonary disease), Charlson Comorbidity Index and risk factors (tobacco use and protracted length of stay in geriatric healthcare facilities) were higher than in COVID patients. The non-COVID-19 pneumonia group showed a higher (24% vs. 17%), although not statistically significant in-hospital mortality rate; the average duration of hospitalization was longer for COVID patients (30 vs. 9 days, p = .0001).ConclusionsIn the early stages of the COVID pandemic, our centre noted no statistical difference in unadjusted in-hospital mortality between COVID and non-COVID patients. Non-COVID patients had higher Charlson Comorbidity Scores, reflecting a greater disease burden in this population.Key MessagesIn March 2020, the COVID-19 disease was declared a pandemic, with enormous consequences for the organization of health systems and in terms of human lives; this has caused the relocation of huge financial resources to departments dedicated to infected patients, at the expense of those suffering from other pathologies.Few published reports have compared COVID-19 and non-COVID-19 pneumonia. In our study, performed in a geographic area with a low prevalence of SARS-CoV-2 infection, we found few statistically significant differences in terms of clinical characteristics between the two groups analyzed.In the early stages of the COVID pandemic, our centre noted no statistical difference in unadjusted in-hospital mortality between COVID and non-COVID patients. Non-COVID patients had higher Charlson Comorbidity Scores, reflecting a greater disease burden in this population.

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Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia.

Publications

Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia.

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