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. 2021 Apr 22:12:592727.
doi: 10.3389/fimmu.2021.592727. eCollection 2021.

Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients

Esmaeil Mortaz  1   2 , Payam Tabarsi  1 , Hamidreza Jamaati  3 , Neda Dalil Roofchayee  2 , Neda K Dezfuli  2   4 , Seyed MohammadReza Hashemian  3 , Afshin Moniri  1 , Majid Marjani  1 , Majid Malekmohammad  3 , Davood Mansouri  1 , Mohammad Varahram  5 , Gert Folkerts  6 , Ian M Adcock  7   8
Affiliations

Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients

Esmaeil Mortaz et al. Front Immunol. .

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm.

Objectives: To elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity.

Methods: We determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran.

Results: Serum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR.

Conclusions: The study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.

Keywords: ARDS; COVID-19; TNF-α; cytokine storm; soluble TNF-α.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Soluble TNF-α receptor I (sTNF-RI) concentrations in the serum of severe COVID-19 patients and healthy subjects. (B) Serum sTNF-RI concentrations in mild COVID-19 patients and healthy subjects. (C) sTNFRI concentrations in the serum of severe COVID-19 patients and mild COVID-19 patients. (D) Serum TNF-α concentrations in mild COVID-19 patients, severe COVID-19 patients and healthy subjects (E) Serum IL-6 concentrations in ICU patients, non-ICU patients and healthy subjects. *P<0.05, **p<0.01, ****P<0.0001 and ns, not significant.
Figure 2
Figure 2
Correlations between serum soluble TNF-α receptor I (sTNFRI) levels in ICU patients with (A) ESR levels and (B) age and (C) between sTNFR1 levels and age in ICU patients and in non-ICU patients and between (D) sTNFRI levels and age in healthy subjects.
See this image and copyright information in PMC

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