Levels of Soluble CD14 and Tumor Necrosis Factor Receptors 1 and 2 May Be Predictive of Death in Severe Coronavirus Disease 2019

Bowman, Emily; Cameron, Cheryl M.; Avery, Ann; Gabriel, Janelle; Kettelhut, Aaren; Hecker, Michelle; Sontich, Claudia Ute; Tamilselvan, Banumathi; Nichols, Carmen N.; Richardson, Brian; Cartwright, Michael; Funderburg, Nicholas T.; Cameron, Mark J.

doi:10.1093/infdis/jiaa744

Cited by 33 publications

(29 citation statements)

References 13 publications

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“…These data highlight disruption in gut barrier integrity as a potential force that may contribute to COVID-19 severity. Our data are compatible with previous reports showed that severe COVID-19 is associated with bacterial translocation to the blood and increased levels of microbial-associated immune activation markers ( 31 , 32 ). Our results do not imply that microbial dysbiosis and translocation are the primary triggers of severe COVID-19, as the complex clinical syndrome of severe COVID-19 likely embodies multiple pathophysiological pathways.…”

Section: Discussionsupporting

confidence: 93%

Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

et al. 2021

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A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.

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Section: Discussionsupporting

confidence: 93%

Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

et al. 2021

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“…Blood-derived prognostic biomarkers for COVID-19 infection have been heavily investigated. Inflammatory and immune factors were among the most widely studied, including serum IL-6 and TNF-α 1 , IFN-α 2 , d-dimer 3 , S100A8/A9 and HMGB1 4 , TNFR1 and TNFR2 5 , acetylated K676 TGFBIp 6 , progranulin (GRN) 7 , and sphingosine-1-phosphate 8 . Other factors include serum GDF-15 9 , calcium 10 , and fasting blood glucose 11 .…”

Section: Introductionmentioning

confidence: 99%

A single transcript for the prognosis of disease severity in COVID-19 patients

Lei

2021

Sci Rep

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With many countries strapped for medical resources due to the COVID-19 pandemic, it is highly desirable to allocate the precious resources to those who need them the most. Several markers have been found to be associated with the disease severity in COVID-19 patients. However, the established markers only display modest prognostic power individually and better markers are urgently needed. The aim of this study is to investigate the potential of S100A12, a prominent marker gene for bacterial infection, in the prognosis of disease severity in COVID-19 patients. To ensure the robustness of the association, a total of 1695 samples from 14 independent transcriptome datasets on sepsis, influenza infection and COVID-19 infection were examined. First, it was demonstrated that S100A12 was a marker for sepsis and severity of sepsis. Then, S100A12 was found to be a marker for severe influenza infection, and there was an upward trend of S100A12 expression as the severity level of influenza infection increased. As for COVID-19 infection, it was found that S100A12 expression was elevated in patients with severe and critical COVID-19 infection. More importantly, S100A12 expression at hospital admission was robustly correlated with future quantitative indexes of disease severity and outcome in COVID-19 patients, superior to established prognostic markers including CRP, PCT, d-dimer, ferritin, LDH and fibrinogen. Thus, S100A12 is a valuable novel prognostic marker for COVID-19 severity and deserves more attention.

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“…Indeed, we observed higher sCD14 in survivors and non-survivors COVID-19 patients. In line with this, Bowman and coworkers (27) found increased . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”

Section: Discussionmentioning

confidence: 60%

“…The copyright holder for this preprint this version posted June 27, 2021. ; https://doi.org/10.1101/2021.06.24.21259468 doi: medRxiv preprint sCD14 levels in COVID-19 patients independent of the disease severity degree. Furthermore, the authors revealed that COVID-19 critical ill patients who recovered or deceased had the highest sCD14 and lipopolysaccharide-binding protein (LBP, another marker of endotoxemia) values compared to the other groups (27). These data underlined the presence of strong activation of the monocytic lineage on hospital admission due to SARS-CoV-2 infection in conjunct with LPS translocation and inflammatory exacerbation in ICU patients (28).…”

Section: Discussionmentioning

confidence: 95%

Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients

Teixeira

Dorneles

Filho

et al. 2021

Preprint

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This study aimed to evaluate the link between microbial translocation markers and systemic inflammation at the earliest time-point after hospitalization and at the last 72 h of hospitalization in survivors and non-survivors COVID-19 patients. Sixty-six SARS-CoV-2 RT-PCR+ infected patients and nine non-COVID-19 pneumonia controls were admitted in this study. Blood samples were collected at hospital admission (T1) (Controls and COVID-19+ patients) and 0-72 h before hospital discharge (T2, alive or dead) to analyze systemic cytokines and chemokines, LPS concentrations, and soluble CD14 (sCD14) levels. THP-1 human monocytic cell line was incubated with plasma from survivors and non-survivors COVID-19 patients and their phenotype, activation status, TLR4, and chemokine receptors were analyzed by flow cytometry. COVID-19 patients presented higher IL-6, IFN-γ, TNF-α, TGF-β1, CCL2/MCP-1, CCL4/MIP-1β, and CCL5/RANTES levels than controls. Moreover, LPS and sCD14 were higher at hospital admission in SARS-CoV-2-infected patients. Non-survivors COVID-19 patients had increased LPS levels concomitant with higher IL-6, TNF-α, CCL2/MCP-1, and CCL5/RANTES levels at T2. Increased expression of CD16 and CCR5 were identified in THP-1 cells incubated with the plasma of survivor patients obtained at T2. The incubation of THP-1 with T2 plasma of non-survivors COVID-19 leads to higher TLR4, CCR2, CCR5, CCR7, and CD69 expression. In conclusion, increased microbial translocation during hospitalization coexist with the inflammatory condition of SARS-CoV-2 infection and could lead to higher monocyte activation in non-survivors COVID-19 patients.

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Levels of Soluble CD14 and Tumor Necrosis Factor Receptors 1 and 2 May Be Predictive of Death in Severe Coronavirus Disease 2019

Cited by 33 publications

References 13 publications

Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

A single transcript for the prognosis of disease severity in COVID-19 patients

Increased LPS levels coexist with systemic inflammation and result in monocyte activation in severe COVID-19 patients

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