Preexisting and inducible endotoxemia as crucial contributors to the severity of COVID-19 outcomes

Kruglikov, Ilja L.; Scherer, Philipp E.

doi:10.1371/journal.ppat.1009306

Cited by 37 publications

(44 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, the exposure of pigs to both porcine respiratory coronavirus and LPS enhanced respiratory disease by increasing the proinflammatory response ( Van Reeth et al, 2000 ). Therefore, it is plausible to think that the LPS pathway might be involved in the development of the severe COVID-19 ( Kruglikov & Scherer, 2021 ) and that IVIG treatment might modulate this pathway. Nevertheless, no major effect on soluble CD14 was observed ( Fig S1 ), which remained at normal levels in IVIG-treated individuals.…”

Section: Resultsmentioning

confidence: 99%

High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients

et al. 2021

View full text Add to dashboard Cite

The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19–affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid–binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status.

show abstract

Section: Resultsmentioning

confidence: 99%

High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In the synthesis domain analysis of lipopolysaccharide, we found that ORF7a had the BPI1 domain (CELYHYQECVR, [15][16][17][18][19][20][21][22][23][24][25]. BPI1 domain (Interpro entry: IPR017942, SMART: SM00328) represents the N-terminal domain found in several lipid-binding serum glycoproteins.…”

Section: Extracellular Orf7a Could Bind To the Cd14 Antigen Moleculementioning

confidence: 99%

“…It shows that SARS-CoV-2 infection causes an increase in endotoxemia of infected individuals. SARS-CoV-2 infection also induces a "leaky gut" state 19 . SARS-CoV-2 RNA is found in stool samples of hospitalized COVID-19 patients, and it reported diarrhea symptoms 20 .…”

Section: Introductionmentioning

confidence: 99%

COVID-19: ABC System and LBP-like Function of ORF7a Activate Monocytes to Induce Diabetes

Liu

2021

Preprint

View full text Add to dashboard Cite

Diabetes and obesity are important factors that make COVID-19 worse. Lipopolysaccharide activates the natural immune system response in obese and diabetic patients' adipose tissue and increases the risk of susceptibility and severity of COVID-19. In this study, bioinformatics techniques such as domain search and molecular docking were used to study the relationship between the ORF7a protein of the SARS-COV-2 virus and lipopolysaccharide. The results show that the transmembrane protein ORF7a has ABC transporter domains: ATP binding and ABC transmembrane domains. The ABC transport domain of ORF7a transported molecules such as metal ions, heme, nucleosides, amino acids, oligopeptides, sugars, vitamins, salts, alkalis etc.. Moreover, it had a multi-drug efflux function. ORF7a also has lipopolysaccharide synthesized domains. It bound the lipopolysaccharide synthesized by ORF7a to CD14 molecule through lipopolysaccharide-binding protein (LBP) to activate CD14 + monocytes. The extracellular ORF7a with the N-terminus and C-terminus cut off still has the BPI11/LBP domain ("CELYHYQECVR") and two ATP-binding motifs ("HYQEC" and "TYEGNS"). The extracellular ORF7a had a similar function of LBP, binding and activating CD14 + monocytes with the help of two ATP-binding structures. We speculated that cells infected by the SARS-COV-2 virus often used its surface lipopolysaccharides to build expanded barriers to resist T cells, NK cells, and drugs. More lipopolysaccharides also activated CD14 + monocytes to release various inflammatory factors, damaging adipose and vascular endothelial tissue to induce diabetes and hypertension.

show abstract

“…The infection is known to induce endotoxemia measured activity in critically ill patients, nearly all of which had evidence of 16S RNA amplification in serum, with proteobacteria the most frequent phylum ( 1 ). Moreover, lipopolysaccharide (LPS) is elevated in patients with obesity and diabetes, known risk factors for COVID-19 infection, and LPS levels are high also in infected patients with cardiac toxicity, and in other viral illnesses, such as human immunodeficiency virus ( 2 ). COVID-19 infection is also associated with thrombotic complications through activation of platelets, endothelial injury from the virus, and abnormal blood flow dynamics ( 3 ).…”

mentioning

confidence: 99%

“…There are also 2 other possible explanations for increased LPS in COVID-19 infection, other than that of altered gut permeability. First, LPS might be induced in susceptible individuals already harboring low levels of endotoxemia ( 2 ). Second, organisms superimposed on SARS-CoV-2 infection, in the lung or elsewhere in the body, could produce LPS ( 1 ).…”

mentioning

confidence: 99%

Is the Intestine a Portal of Entry for the Serious COVID-19 Complications of Endotoxemia and Thrombosis?

Alpers

2021

Clin Transl Gastroenterol

View full text Add to dashboard Cite

: Severe acute respiratory syndrome coronavirus 2 infection has been associated with both endotoxemia and thrombosis of small and large vessels, but the relationship between these 2 phenomena has not been pursued. Oliva et al. in this issue of Clinical and Translational Gastroenterology demonstrate an association between the 2 findings and suggest that increased intestinal permeability is a possible mechanism to explain the endotoxemia. Although the evidence to support this hypothesis is only suggestive, the role of the small intestine in the illness produced by the virus needs to be further explored.

show abstract

Preexisting and inducible endotoxemia as crucial contributors to the severity of COVID-19 outcomes

Cited by 37 publications

References 28 publications

High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients

High-dose intravenous immunoglobulins might modulate inflammation in COVID-19 patients

COVID-19: ABC System and LBP-like Function of ORF7a Activate Monocytes to Induce Diabetes

Is the Intestine a Portal of Entry for the Serious COVID-19 Complications of Endotoxemia and Thrombosis?

Contact Info

Product

Resources

About