Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.

<h4>Background</h4>Although hyperinflammatory response influences the severity of coronavirus disease 2019 (COVID-19), little has been reported about the utility of tumor necrosis factor (TNF)-related biomarkers in reflecting the prognosis. We examined whether TNF receptors (TNFRs: TNFR1...

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Main Authors: Tomohito Gohda, Maki Murakoshi, Yusuke Suzuki, Makoto Hiki, Toshio Naito, Kazuhisa Takahashi, Yoko Tabe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0275745
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author Tomohito Gohda
Maki Murakoshi
Yusuke Suzuki
Makoto Hiki
Toshio Naito
Kazuhisa Takahashi
Yoko Tabe
author_facet Tomohito Gohda
Maki Murakoshi
Yusuke Suzuki
Makoto Hiki
Toshio Naito
Kazuhisa Takahashi
Yoko Tabe
author_sort Tomohito Gohda
collection DOAJ
description <h4>Background</h4>Although hyperinflammatory response influences the severity of coronavirus disease 2019 (COVID-19), little has been reported about the utility of tumor necrosis factor (TNF)-related biomarkers in reflecting the prognosis. We examined whether TNF receptors (TNFRs: TNFR1, TNFR2) and progranulin (PGRN) levels, in addition to interleukin 6 (IL-6) and C-reactive protein (CRP), are associated with mortality or disease severity in COVID-19 patients.<h4>Methods</h4>This retrospective study was conducted at Juntendo University Hospital. Eighty hospitalized patients with various severities of COVID-19 were enrolled. Furthermore, serum levels of TNF-related biomarkers were measured using enzyme-linked immunosorbent assay.<h4>Results</h4>Twenty-five patients died during hospitalization, and 55 were discharged. The median (25th and 75th percentiles) age of the study patients was 70 (61-76) years, 44 (55.0%) patients were males, and 26 (32.5%) patients had chronic kidney disease (CKD). When comparing with patients who received and did not receive treatment at the intensive care unit (ICU), the former had a higher tendency of being male and have diabetes, hypertension, and CKD; had higher levels of white blood cells, D-dimer, and lactate dehydrogenase; and had lower body mass index, estimated glomerular filtration rate, and lymphocyte counts. Significant differences were observed in TNFR, PGRN, IL-6, and CRP levels between each severity (mild-severe) group. Furthermore, the serum levels of TNFR, IL-6, and CRP, but not PGRN, in ICU patients were significantly higher than in the patients who were not admitted to the ICU. Multivariate logistic regression analysis demonstrated that high levels of TNFR2 were only associated with mortality in patients with COVID-19 even after adjustment for relevant clinical parameters.<h4>Conclusions</h4>High TNFR2 level might be helpful for predicting mortality or disease severity in patients with COVID-19.
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spelling doaj.art-33ceffc8e9434a37b8a7700543f2a9dd2022-12-22T02:32:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011710e027574510.1371/journal.pone.0275745Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.Tomohito GohdaMaki MurakoshiYusuke SuzukiMakoto HikiToshio NaitoKazuhisa TakahashiYoko Tabe<h4>Background</h4>Although hyperinflammatory response influences the severity of coronavirus disease 2019 (COVID-19), little has been reported about the utility of tumor necrosis factor (TNF)-related biomarkers in reflecting the prognosis. We examined whether TNF receptors (TNFRs: TNFR1, TNFR2) and progranulin (PGRN) levels, in addition to interleukin 6 (IL-6) and C-reactive protein (CRP), are associated with mortality or disease severity in COVID-19 patients.<h4>Methods</h4>This retrospective study was conducted at Juntendo University Hospital. Eighty hospitalized patients with various severities of COVID-19 were enrolled. Furthermore, serum levels of TNF-related biomarkers were measured using enzyme-linked immunosorbent assay.<h4>Results</h4>Twenty-five patients died during hospitalization, and 55 were discharged. The median (25th and 75th percentiles) age of the study patients was 70 (61-76) years, 44 (55.0%) patients were males, and 26 (32.5%) patients had chronic kidney disease (CKD). When comparing with patients who received and did not receive treatment at the intensive care unit (ICU), the former had a higher tendency of being male and have diabetes, hypertension, and CKD; had higher levels of white blood cells, D-dimer, and lactate dehydrogenase; and had lower body mass index, estimated glomerular filtration rate, and lymphocyte counts. Significant differences were observed in TNFR, PGRN, IL-6, and CRP levels between each severity (mild-severe) group. Furthermore, the serum levels of TNFR, IL-6, and CRP, but not PGRN, in ICU patients were significantly higher than in the patients who were not admitted to the ICU. Multivariate logistic regression analysis demonstrated that high levels of TNFR2 were only associated with mortality in patients with COVID-19 even after adjustment for relevant clinical parameters.<h4>Conclusions</h4>High TNFR2 level might be helpful for predicting mortality or disease severity in patients with COVID-19.https://doi.org/10.1371/journal.pone.0275745
spellingShingle Tomohito Gohda
Maki Murakoshi
Yusuke Suzuki
Makoto Hiki
Toshio Naito
Kazuhisa Takahashi
Yoko Tabe
Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.
PLoS ONE
title Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.
title_full Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.
title_fullStr Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.
title_full_unstemmed Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.
title_short Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.
title_sort circulating tumor necrosis factor receptors are associated with mortality and disease severity in covid 19 patients
url https://doi.org/10.1371/journal.pone.0275745
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