A Promising Anti-Cytokine-Storm Targeted Therapy for COVID-19: The Artificial-Liver Blood-Purification System

Zhang, Yimin; Yu, Liang; Tang, Linlin; Zhu, Mengfei; Jin, Yinzhe; Wang, Zhouhan; Li, Lanjuan

doi:10.1016/j.eng.2020.03.006

Cited by 67 publications

(74 citation statements)

References 23 publications

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“…These risk factors might compromise and deteriorate the patients' clinical outcome. Based on our results, it seems that hemoperfusion can be bene cial in management of uid overload, metabolic disorder, and cardiovascular dysfunction, besides to reduction of in ammatory mediators; as was mentioned in previous studies (25).…”

Section: Discussionsupporting

confidence: 81%

Effectiveness of extracorporeal blood purification (hemoadsorption) in patients with severe coronavirus disease 2019 (COVID-19)

Asgharpour

Mehdinezhad

Bayani

et al. 2020

Preprint

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Background Extracorporeal blood purification has been proposed as one of the therapeutic approaches in patients with coronavirus infection, because of its beneficial impact on elimination of inflammatory cytokines. Methods This controlled trial has been conducted on critically ill COVID-19 patients admitted in the state hospital affiliated to Babol University of Medical Sciences, Iran who received different antiviral and antibacterial drugs, and different modalities of respiratory treatments and did not have positive clinical improvement. No randomization and blindness was considered. All of the participants underwent three sessions of resin-directed hemoperfusion using continuous renal replacement therapy with a mode of continuous venovenous hemofiltration (CVVH). Results Five men and five women with a mean age of 57.30±18.07 years have been enrolled in the study; and six of them have improved after the intervention. Peripheral capillary oxygen saturation (SpO2) changed after each session. Mean SpO2 before the three sessions of hemoperfusion was 89.60%±3.94% and increased to 92.13%±3.28% after them (p<0.001). Serum IL-6 showed a reduction from 139.70±105.62 to 72.06±65.87 pg/mL (p=0.073); and c-reactive protein increased from 136.25±84.39 to 78.25±38.67 mg/L (P=0.016). Conclusions Extracorporeal hemoadsorption could improve the general condition in most of recruited patients with severe coronavirus disease; however, large prospective multicenter trials in carefully selected patients are needed to definitely evaluate the efficacy of hemoperfusion in COVID-19 patients.

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Section: Discussionsupporting

confidence: 81%

Effectiveness of extracorporeal blood purification (hemoadsorption) in patients with severe coronavirus disease 2019 (COVID-19)

Asgharpour

Mehdinezhad

Bayani

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Kidney proximal tubule cells with ACE2-positive expression showed some relevant biological events for the mechanisms of injury, including virus regulation, autophagy regulation, and immune and kidney water homeostasis pathways by GSEA. Secondly, the elevated cytokines in infected patients could result in aberrant immune responses and local damage via binding with cytokine receptors in fenestrated and glomerular endothelial cells 38 . This damage would impair the function of the renal glomerular filtration barrier and could feasibly account for the observed abnormalities in serum creatinine and proteinuria.…”

Section: Discussionmentioning

confidence: 99%

Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19

Ren

Wei

et al. 2020

Preprint

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Background: Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. From previously published evidence, ACE2 and TMPRSS2, are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Meanwhile, increased expression of pro-inflammatory cytokines, or a "cytokine storm," is associated with multiple organ dysfunction syndrome that is often observed in critically ill patients. Methods: We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially under specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2 specific signature. Results: Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis, and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were remarkably concentrated in endothelial cells, macrophages, and spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging mechanisms via autoimmune attacks. Conclusions: This study provided new insights into the pathogenicity mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.

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“…In summary, most of the severe/critical patients presented the increase of neutrophil percentage, procalcitonin, and the decrease of lymphocyte percentage, which may potentially induce a cytokine storm in the body, and generate a series of immune responses to damage the corresponding organs 12,20 .…”

Section: Identification Of Laboratory Indicators Related To the Severmentioning

confidence: 99%

Laboratory Testing Implications of Risk-Stratification and Management for Improving Clinical Outcomes of COVID-19 Patients

Liu

Wang

et al. 2020

Preprint

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The high mortality rate of COVID-19 patients is mainly caused by the progression from mild to critical illness. To identify the key laboratory indicators and stratify high-risk COVID-19 patients with progression to severe/critical illness, we compared 474 moderate patients and 74 severe/critical patients. The laboratory indicators, including lactate dehydrogenase (LDH), monocytes percentage, etc. were significantly higher in the severe/critical patients (P <0.001) and showed a noticeable change at about a week before the diagnosis. Based on these indicators, we constructed a risk-stratification model, which can accurately grade the severity of patients with COVID-19 (accuracy = 0.96, 95% CI: 0.94 - 0.989, sensitivity = 0.98, specificity = 0.84). Also, compared with non-COVID-19 viral pneumonia, we found that COVID-19 had weaker dysfunction to the heart, liver, and kidney. The prognostic model based on laboratory indicators could help to diagnose, monitor, and predict severity at an early stage to those patients with COVID-19.

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A Promising Anti-Cytokine-Storm Targeted Therapy for COVID-19: The Artificial-Liver Blood-Purification System

Cited by 67 publications

References 23 publications

Effectiveness of extracorporeal blood purification (hemoadsorption) in patients with severe coronavirus disease 2019 (COVID-19)

Effectiveness of extracorporeal blood purification (hemoadsorption) in patients with severe coronavirus disease 2019 (COVID-19)

Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19

Laboratory Testing Implications of Risk-Stratification and Management for Improving Clinical Outcomes of COVID-19 Patients

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