Dataset Information

Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity.

ABSTRACT:

Objectives

We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases.

Methods

We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry.

Results

The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4⁺ and CD8⁺ T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4⁺ or CD8⁺ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in the severe group.

Conclusions

Severe COVID-19 had a higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.

SUBMITTER: Kang CK

PROVIDER: S-EPMC7261468 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity.

Kang Chang Kyung CK Han Gi-Chan GC Kim Minji M Kim Gwanghun G Shin Hyun Mu HM Song Kyoung-Ho KH Choe Pyoeng Gyun PG Park Wan Beom WB Kim Eu Suk ES Kim Hong Bin HB Kim Nam-Joong NJ Kim Hang-Rae HR Oh Myoung-Don MD

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 20200531

<h4>Objectives</h4>We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases.<h4>Methods</h4>We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤93% at room air. Expressions of molecules r ...[more]

PMID: 32492530

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Project description:BackgroundGenetic predisposition to COVID-19 may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity.AimTo determine associations of common functional polymorphisms in MIF with symptomatic COVID-19 or its severity.MethodsThis retrospective case control study utilized 1171 patients with COVID-19 from three tertiary medical centers in the United States, Hungary, and Spain, together with a group of 637 pre-pandemic, healthy control subjects. Functional MIF promoter alleles (-794 CATT5-8, rs5844572), serum MIF and soluble MIF receptor levels, and available clinical characteristics were measured and correlated with COVID-19 diagnosis and hospitalization. Experimental mice genetically engineered to express human high- or low-expression MIF alleles were studied for response to coronavirus infection.ResultsIn patients with COVID-19, there was a lower frequency of the high-expression MIF CATT7 allele when compared to healthy controls (11% vs. 19%, OR: 0.54 [0.41, 0.72], p < 0.0001). Among inpatients with COVID-19 (n = 805), there was a higher frequency of the MIF CATT7 allele compared to outpatients (n = 187) (12% vs. 5%, OR: 2.87 [1.42, 5.78], p = 0.002). Inpatients presented with higher serum MIF levels when compared to outpatients or uninfected healthy controls (87 ng/ml vs. 35 ng/ml vs. 29 ng/ml, p < 0.001, respectively). Among inpatients, circulating MIF concentrations correlated with admission ferritin (r = 0.19, p = 0.01) and maximum CRP (r = 0.16, p = 0.03) levels. Mice with a human high-expression MIF allele showed more severe disease than those with a low-expression MIF allele.ConclusionsIn this multinational retrospective study of 1171 subjects with COVID-19, the commonly occurring -794 CATT7 MIF allele is associated with reduced susceptibility to symptomatic SARS-CoV-2 infection but increased disease progression as assessed by hospitalization. These findings affirm the importance of host genetics in different stages of COVID-19 infection.

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Dataset Information

Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity.

Objectives

Methods

Results

Conclusions

Publications

Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity.

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