High Levels of Circulating IL-8 and Soluble IL-2R Are Associated With Prolonged Illness in Patients With Severe COVID-19

Ma, Anqi; Zhang, Liang; Ye, Xiaokai; Chen, Jing; Yu, Jie; Zhuang, Liangjin; Weng, Chaohang; Petersen, Frank; Wang, Zhanxiang; Yu, Xinhua

doi:10.3389/fimmu.2021.626235

Cited by 66 publications

(45 citation statements)

References 30 publications

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“…However, the CRP levels were gently reduced from day 0 to day 6 in both groups of patients. Our finding confirms previous investigations demonstrating that the IL-6 [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , IL-8 [51] , [52] , [53] , [54] , and CRP [55] , [56] were significantly elevated in patients with COVID-19. Besides, our results revealed that the concentrations of IL-4 and IL-10 were significantly elevated in cases with COVID-19 than in HS.…”

Section: Discussionsupporting

confidence: 92%

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19)

Karampoor

Hesamizadeh

Maleki

et al. 2021

International Immunopharmacology

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A growing body of evidence indicates that neutrophil elastase (NE) is involved in the pathogenesis of respiratory infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to analyze the dynamic changes in serum levels of NE associated with inflammation, disease activity, and mortality rate in patients with COVID-19. We measured the serum concentrations of NE, C-Reactive protein (CRP), interleukin (IL)- 4, IL-6, IL-8, IL-10, and vitamin D levels in 83 ICU and 69 non-ICU patients compared with 82 healthy subjects (HS) in three-time points (T1-T3). Serum levels of NE, IL-6, IL-8, and CRP in ICU and non-ICU patients were significantly higher than HS ( P <0.001) in three-time points. Also, serum levels of NE, IL-6, IL-8, and CRP in ICU patients were significantly higher than in non-ICU patients ( P <0.05). On the day of admission (T1), the levels of NE, CRP, IL-6, IL-8 were gradually decreased from T1 to T3. At the same time, IL-4 and IL-10 were gradually increased from T1 to T2 and then reduced to T3. Further analyses demonstrated that the levels of NE, IL-6, and IL-8 in deceased patients were significantly higher than in recovered patients ( P <0.05). The ROC curve analysis demonstrated that markers, including NE, IL-6, and IL-8, were valuable indicators in evaluating the activity of COVID-19. Overall, our results signify the critical role of NE in the pathogenesis of COVID-19, and also, further support that NE has a potential therapeutic target for the attenuation of COVID-19 severity.

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Section: Discussionsupporting

confidence: 92%

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19)

Karampoor

Hesamizadeh

Maleki

et al. 2021

International Immunopharmacology

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“…IL-8 is a neutrophil chemotactic factor. High levels of serum IL-8 and an increased neutrophil-to-lymphocyte ratio are associated with the illness severity of COVID-19 [ 45 ]. In this study, we observed that low levels of IL-8 are induced by MERS S1-Fc, SARS CoV-1 S1-Fc, SARS CoV-2 S1-Fc (Vendor #1, lot 24529-2003) and SARS CoV-2 RBD-Fc (Vendor #2 and Vendor #1, lot 25130-2004) ( Figure 2 and Figure S2 ), which do not induce expression of other inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Variable Induction of Pro-Inflammatory Cytokines by Commercial SARS CoV-2 Spike Protein Reagents: Potential Impacts of LPS on In Vitro Modeling and Pathogenic Mechanisms In Vivo

Ouyang

Xie

Fang

et al. 2021

IJMS

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Proinflammatory cytokine production following infection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is associated with poor clinical outcomes. Like SARS CoV-1, SARS CoV-2 enters host cells via its spike protein, which attaches to angiotensin-converting enzyme 2 (ACE2). As SARS CoV-1 spike protein is reported to induce cytokine production, we hypothesized that this pathway could be a shared mechanism underlying pathogenic immune responses. We herein compared the capabilities of Middle East Respiratory Syndrome (MERS), SARS CoV-1 and SARS CoV-2 spike proteins to induce cytokine expression in human peripheral blood mononuclear cells (PBMC). We observed that only specific commercial lots of SARS CoV-2 induce cytokine production. Surprisingly, recombinant SARS CoV-2 spike proteins from different vendors and batches exhibited different patterns of cytokine induction, and these activities were not inhibited by blockade of spike protein-ACE2 binding using either soluble ACE2 or neutralizing anti-S1 antibody. Moreover, commercial spike protein reagents contained varying levels of lipopolysaccharide (LPS), which correlated directly with their abilities to induce cytokine production. The LPS inhibitor, polymyxin B, blocked this cytokine induction activity. In addition, SARS CoV-2 spike protein avidly bound soluble LPS in vitro, rendering it a cytokine inducer. These results not only suggest caution in monitoring the purity of SARS CoV-2 spike protein reagents, but they indicate the possibility that interactions of SARS CoV-2 spike protein with LPS from commensal bacteria in virally infected mucosal tissues could promote pathogenic inflammatory cytokine production.

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“…6,7 Individual markers like IL-6, IL-8 or patterns from multi-omics analysis have been associated with disease severity and lethality. [8][9][10][11][12] Pathological findings implicated that the plasminogenplasmin system is involved in the progression of the disease. 13,14 Diffuse alveolar lesions, microthrombi and frequent hemorrhage in the alveolar region were observed in autopsied patients.…”

Section: Introductionmentioning

confidence: 99%

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19

Herr¹,

Mang²,

Mozafari³

et al. 2021

JIR

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Background: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements.Patients and Methods: Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. Results: The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). Discussion: Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

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High Levels of Circulating IL-8 and Soluble IL-2R Are Associated With Prolonged Illness in Patients With Severe COVID-19

Cited by 66 publications

References 30 publications

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19)

A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19)

Variable Induction of Pro-Inflammatory Cytokines by Commercial SARS CoV-2 Spike Protein Reagents: Potential Impacts of LPS on In Vitro Modeling and Pathogenic Mechanisms In Vivo

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19

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