Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study

Gong, Jing; Dong, Hui; Qing, Xiao; Huang, Zhaoyi; Wang, Ding-kun; Zhao, Yan; Liu, Wenhua; Tu, Shenghao; Zhang, Mingmin; Wang, Qi; Lu, Fanghong

doi:10.1186/s12879-020-05681-5

Cited by 225 publications

(166 citation statements)

References 11 publications

Supporting

Mentioning

145

Contrasting

Unclassified

Order By: Relevance

“…Several clinical studies have reported that hyper-inflammation, accompanied by increased serum levels of pro-inflammatory cytokines and chemokines, is associated with disease severity and death in COVID-19 [ 14 , 20 – 22 ]. In fact, post-mortem analyses have revealed that high levels of pro-inflammatory cytokines are associated with cellular infiltration of organs such as the lungs, heart and kidney [ 14 , 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Induction of Exaggerated Cytokine Production in Human Peripheral Blood Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by Dexamethasone

et al. 2021

View full text Add to dashboard Cite

An understanding of the pathological inflammatory mechanisms involved in SARS-CoV-2 virus infection is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 cytokine storm. In this study, the effects of a recombinant SARS-CoV-2 spike glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation of PBMCs with spike glycoprotein S1 (100 ng/mL) resulted in significant elevation in the production of TNFα, IL-6, IL-1β and IL-8. However, pre-treatment with dexamethasone (100 nM) caused significant reduction in the release of these cytokines. Further experiments revealed that S1 stimulation of PBMCs increased phosphorylation of NF-κB p65 and IκBα, and IκBα degradation. DNA binding of NF-κB p65 was also significantly increased following stimulation with spike glycoprotein S1. Treatment of PBMCs with dexamethasone (100 nM) or BAY11-7082 (1 μM) resulted in inhibition of spike glycoprotein S1-induced NF-κB activation. Activation of p38 MAPK by S1 was blocked in the presence of dexamethasone and SKF 86002. CRID3, but not dexamethasone pre-treatment, produced significant inhibition of S1-induced activation of NLRP3/caspase-1. Further experiments revealed that S1-induced increase in the production of TNFα, IL-6, IL-1β and IL-8 was reduced in the presence of BAY11-7082 and SKF 86002, while CRID3 pre-treatment resulted in the reduction of IL-1β production. These results suggest that SARS-CoV-2 spike glycoprotein S1 stimulated PBMCs to release pro-inflammatory cytokines through mechanisms involving activation of NF-κB, p38 MAPK and NLRP3 inflammasome. It is proposed that the clinical benefits of dexamethasone in COVID-19 are possibly due to its anti-inflammatory activity in reducing SARS-CoV-2 cytokine storm.

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of Exaggerated Cytokine Production in Human Peripheral Blood Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by Dexamethasone

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The cytokine storm may eventually lead to severe illness or death, in both sepsis and as observed in the current COVID-19 pandemic ( 51 , 52 ). Furthermore, levels of IL-6 in severely ill patients were found to have increased significantly and were associated with a poor prognosis ( 53 , 54 ). Corticosteroids and non-steroidal anti-inflammatory drugs are commonly used to treat inflammation.…”

Section: Discussionmentioning

confidence: 99%

MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway

et al. 2021

View full text Add to dashboard Cite

Sepsis is a heterogeneous syndrome caused by a dysregulated host response during the process of infection. Neutrophils are involved in the development of sepsis due to their essential role in host defense. COVID-19 is a viral sepsis. Disfunction of neutrophils in sepsis has been described in previous studies, however, little is known about the role of microRNA-let-7b (miR-let-7b), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) activity in neutrophils and how they participate in the development of sepsis. In this study, we investigated the regulatory pathway of miR-let-7b/TLR4/NF-κB in neutrophils. We also explored the downstream cytokines released by neutrophils following miR-let-7b treatment and its therapeutic effects in cecal ligation and puncture (CLP)-induced septic mice. Six-to-eight-week-old male C57BL/6 mice underwent CLP following treatment with miR-let-7b agomir. Survival (n=10), changes in liver and lungs histopathology (n=4), circulating neutrophil counts (n=4), the liver-body weight ratio (n=4–7), and the lung wet-to-dry ratio (n=5–6) were recorded. We found that overexpression of miR-let-7b could significantly down-regulate the expression of human-derived neutrophilic TLR4 at a post-transcriptional level, a decreased level of proinflammatory factors including interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and an upregulation of anti-inflammatory factor IL-10 in vitro. After miR-let-7b agomir treatment in vivo, neutrophil recruitment was inhibited and thus the injuries of liver and lungs in CLP-induced septic mice were alleviated (p=0.01 and p=0.04, respectively), less weight loss was reduced, and survival in septic mice was also significantly improved (p=0.013). Our study suggested that miR-let-7b could be a potential target of sepsis.

show abstract

“…Furthermore, our results provide markers that could be potentially be valuable in monitoring the progression of SARS-CoV-2 infection and assessing therapeutic strategies to promote viral clearance and restore normal intestinal function. Among the protein functions described, some such as Galectin-9 and CRP are already under investigation as biomarkers of disease severity [38][39][40] . Interestingly, elevated serum levels of CRP, especially in association with a high concentration of D-dimers, are reported to be indicative of an increased risk of adverse outcomes in COVID-19 41 .…”

Section: Discussionmentioning

confidence: 99%

Taxonomical and functional changes in COVID-19 faecal microbiome are related to SARS-CoV-2 faecal load

Armengaud

Grenga

Pible³

et al. 2021

Preprint

View full text Add to dashboard Cite

Since the beginning of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the gastro-intestinal (GI) tract has emerged as an important organ influencing the propensity to and potentially severity of the related COVID-19 disease. However, the contribution of the SARS-CoV-2 intestinal infection on COVID-19 pathogenesis remains to be clarified. In this exploratory study, we evidenced that alterations in the composition of the gut microbiota depends on the levels of SARS-CoV-2 RNA in the gastrointestinal tract but not on the presence of SARS-CoV-2 in the respiratory tract, COVID-19 severity and GI symptoms. Altered molecular functions in the microbiota profiles of high SARS-CoV-2 RNA level faeces as established by metaproteomics highlight mechanisms that may contribute to vicious cycles. Uncovering the role of this gut microbiota dysbiosis could drive the investigation of alternative therapeutic strategies to favour the clearance of the virus and potentially mitigate the effect of SARS-CoV-2 infection.

show abstract

Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study

Cited by 225 publications

References 11 publications

Induction of Exaggerated Cytokine Production in Human Peripheral Blood Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by Dexamethasone

Induction of Exaggerated Cytokine Production in Human Peripheral Blood Mononuclear Cells by a Recombinant SARS-CoV-2 Spike Glycoprotein S1 and Its Inhibition by Dexamethasone

MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway

Taxonomical and functional changes in COVID-19 faecal microbiome are related to SARS-CoV-2 faecal load

Contact Info

Product

Resources

About