Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection
Coronavirus disease 2019 (COVID-19) has been a pandemic for the past two years. Predicting patient prognosis is critical. Although immune checkpoints (ICs) were shown to be involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, quantitative studies of ICs in clinical pra...
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Frontiers Media S.A.
2022-08-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.903419/full |
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author | Nuri Lee Seri Jeong Kibum Jeon Min-Jeong Park Wonkeun Song |
author_facet | Nuri Lee Seri Jeong Kibum Jeon Min-Jeong Park Wonkeun Song |
author_sort | Nuri Lee |
collection | DOAJ |
description | Coronavirus disease 2019 (COVID-19) has been a pandemic for the past two years. Predicting patient prognosis is critical. Although immune checkpoints (ICs) were shown to be involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, quantitative studies of ICs in clinical practice are limited. In this study, various soluble ICs (sICs) and cytokine levels in patients with SARS-CoV-2 infection at different time points were compared between survivors and deaths; we also examined whether sICs are useful for predicting prognosis. sICs and cytokines were measured in serum samples from 38 patients diagnosed with COVID-19 in the first and second week post-diagnosis. All assays were performed by bead-based multiplexed immunoassay system using Luminex Bio-Plex 200 system. The correlation of sICs and cytokines with laboratory markers was evaluated, and the levels of sICs in survivors were compared with those in deaths. Among the sICs, the second-week levels of soluble cluster of differentiation (sCD27, p = 0.012), sCD40 (p< 0.001), cytotoxic T-lymphocyte-associated protein 4 (sCTLA-4, p< 0.001), herpes virus entry mediator (sHVEM, p = 0.026), and T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3, p = 0.002) were significantly higher in deaths than in survivors. The levels of nine cytokines assessed in the second week of deaths were significantly higher than those in survivors. The sICs sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines chemokine CC motif ligand 2 (CCL2), GM-CSF, IL-10, and IL-8 showed significant positive correlations with the levels of C-reactive protein (CRP) and procalcitonin and were negatively correlated with the absolute lymphocyte count and platelet values. Increased levels of sICs including sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines were significant factors for poor prognosis. sICs, together with cytokines and inflammatory markers, may be useful as prognostic stratification markers in SARS-CoV-2-infected patients. |
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issn | 1664-3224 |
language | English |
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publishDate | 2022-08-01 |
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spelling | doaj.art-af0604fde63b4fdd9518656f0a1c5caa2022-12-22T03:44:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.903419903419Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infectionNuri Lee0Seri Jeong1Kibum Jeon2Min-Jeong Park3Wonkeun Song4Department of Laboratory Medicine, Hallym University College of Medicine, Seoul, South KoreaDepartment of Laboratory Medicine, Hallym University College of Medicine, Seoul, South KoreaDepartment of Laboratory Medicine, Hallym University College of Medicine, Hangang Sacred Heart Hospital, Seoul, South KoreaDepartment of Laboratory Medicine, Hallym University College of Medicine, Seoul, South KoreaDepartment of Laboratory Medicine, Hallym University College of Medicine, Seoul, South KoreaCoronavirus disease 2019 (COVID-19) has been a pandemic for the past two years. Predicting patient prognosis is critical. Although immune checkpoints (ICs) were shown to be involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, quantitative studies of ICs in clinical practice are limited. In this study, various soluble ICs (sICs) and cytokine levels in patients with SARS-CoV-2 infection at different time points were compared between survivors and deaths; we also examined whether sICs are useful for predicting prognosis. sICs and cytokines were measured in serum samples from 38 patients diagnosed with COVID-19 in the first and second week post-diagnosis. All assays were performed by bead-based multiplexed immunoassay system using Luminex Bio-Plex 200 system. The correlation of sICs and cytokines with laboratory markers was evaluated, and the levels of sICs in survivors were compared with those in deaths. Among the sICs, the second-week levels of soluble cluster of differentiation (sCD27, p = 0.012), sCD40 (p< 0.001), cytotoxic T-lymphocyte-associated protein 4 (sCTLA-4, p< 0.001), herpes virus entry mediator (sHVEM, p = 0.026), and T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3, p = 0.002) were significantly higher in deaths than in survivors. The levels of nine cytokines assessed in the second week of deaths were significantly higher than those in survivors. The sICs sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines chemokine CC motif ligand 2 (CCL2), GM-CSF, IL-10, and IL-8 showed significant positive correlations with the levels of C-reactive protein (CRP) and procalcitonin and were negatively correlated with the absolute lymphocyte count and platelet values. Increased levels of sICs including sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines were significant factors for poor prognosis. sICs, together with cytokines and inflammatory markers, may be useful as prognostic stratification markers in SARS-CoV-2-infected patients.https://www.frontiersin.org/articles/10.3389/fimmu.2022.903419/fullimmune checkpointCOVID-19cytokine release syndromeSARS-CoV-2prognosis |
spellingShingle | Nuri Lee Seri Jeong Kibum Jeon Min-Jeong Park Wonkeun Song Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection Frontiers in Immunology immune checkpoint COVID-19 cytokine release syndrome SARS-CoV-2 prognosis |
title | Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection |
title_full | Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection |
title_fullStr | Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection |
title_full_unstemmed | Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection |
title_short | Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection |
title_sort | prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with sars cov 2 infection |
topic | immune checkpoint COVID-19 cytokine release syndrome SARS-CoV-2 prognosis |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.903419/full |
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