Cytokine storm and the prospects for immunotherapy with COVID-19

Calabrese, Leonard H.

doi:10.3949/ccjm.87a.ccc008

Cited by 45 publications

(53 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…54 In particular, IL-6, IL-17, and IL-8 are synergistically responsible for pulmonary fibrosis (promoting collagen deposition) secondary to aberrant fibroblast and epithelial cell function or pleural effusion of the lung, and viral persistence results in dyspnea and provokes SARS ( Figure 2). 55 I suggest that the presence of these cells may be a primary driver of the signature pathology observed in COVID-19 patients. Taken together, IL-17-induced dysregulated and exuberant immune responses have been shown to potentially cause stage 3 (characterized by a hyperinflammatory phase, cytokine storm) COVID-19 disease, likely through increased pulmonary pathology or lung damage and diminished survival.…”

Section: Il-17a Signaling and Pathological Effects During Covid-19mentioning

confidence: 98%

<p>Inflammatory Cytokine: IL-17A Signaling Pathway in Patients Present with COVID-19 and Current Treatment Strategy</p>

Shibabaw¹

2020

JIR

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) is a globally communicable public health disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Eradication of COVID-19 appears practically impossible but, therefore, more effective pharmacotherapy is needed. The deteriorated clinical presentation of patients with COVID-19 is mainly associated with hypercytokinemia due to notoriously elevated pro-inflammatory cytokines such as interleukin (IL)-1B, IL-6, IL-8, IL-17, granulocyte-macrophage colonystimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-γinducible protein (IP10), monocyte chemoattractant protein (MCP1), and tumor necrosis factor-α (TNFα), and is usually responsible for cytokine release syndrome. In the cytokine storm, up-regulation of T-helper 17 cell cytokine IL-17A, and maybe also IL-17F, is mostly responsible for the immunopathology of COVID-19 and acute respiratory distress syndrome. Herein, I meticulously review the exuberant polarization mechanism of naïve CD4 + T cells toward Th17 cells in response to SARS-CoV-2 infection and its associated immunopathological sequelae. I also, propose, for clinical benefit, targeting IL-17A signaling and the synergic inflammatory cytokine IL-6 to manage COVID-19 patients, particularly those presenting with cytokine storm syndrome.

show abstract

Section: Il-17a Signaling and Pathological Effects During Covid-19mentioning

confidence: 98%

<p>Inflammatory Cytokine: IL-17A Signaling Pathway in Patients Present with COVID-19 and Current Treatment Strategy</p>

Shibabaw¹

2020

JIR

View full text Add to dashboard Cite

show abstract

“…[28][29][30][31] This is relevant to COVID-19, which is similarly strongly associated with vascular thrombosis and inflammation. [32][33][34][35]…”

Section: Lectin Alternativementioning

confidence: 99%

“…Although many of these patients have elevated D-dimer and fibrinogen, they also commonly have increased C-reactive protein and IL-6, consistent with a vigorous inflammatory response. 35 The thrombopathy may be a response to direct virus-induced damage to vascular endothelial cells 64 and/or the virus acquiring TF from host cells, both triggering coagulation activation. 50,52,53,71…”

Section: Does Complement Activation Trigger Venous Thromboembolism mentioning

confidence: 99%

“…Notably, it is these pro-inflammatory cytokines that are characteristically elevated in severe COVID-19, eliciting the so-called "cytokine storm. "35 Themechanisms underlying the prominent COVID-19-associated hyper-inflammatory response are not well understood. However, excess complement activation by itself is not a plausible explanation, as this phenomenon is not observed in aHUS.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Is the COVID‐19 thrombotic catastrophe complement‐connected?

Conway

Pryzdial

2020

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

In December 2019, the world was introduced to a new betacoronavirus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for its propensity to cause rapidly progressive lung damage, resulting in high death rates. As fast as the virus spread, it became evident that the novel coronavirus causes a multisystem disease (COVID-19) that may involve multiple organs and has a high risk of thrombosis associated with striking elevations in pro-inflammatory cytokines, D-dimer, and fibrinogen, but without disseminated intravascular coagulation. Postmortem studies have confirmed the high incidence of venous thromboembolism, but also notably revealed diffuse microvascular thrombi with endothelial swelling, consistent with a thrombotic microangiopathy, and inter-alveolar endothelial deposits of complement activation fragments. The clinicopathologic presentation of COVID-19 thus parallels that of other thrombotic diseases, such as atypical hemolytic uremic syndrome (aHUS), that are caused by dysregulation of the complement system. This raises the specter that many of the thrombotic complications arising from SARS-CoV-2 infections may be triggered and/or exacerbated by excess complement activation. This is of major potential clinical relevance, as currently available anti-complement therapies that are highly effective in protecting against thrombosis in aHUS, could be efficacious in COVID-19. In this review, we provide mounting evidence for complement participating in the pathophysiology underlying the thrombotic diathesis associated with pathogenic coronaviruses, including SARS-CoV-2. Based on current knowledge of complement, coagulation and the virus, we suggest lines of study to identify novel therapeutic targets and the rationale for clinical trials with currently available anticomplement agents for COVID-19.

show abstract

“…In the first two parts of this series, we focused on the basic immunobiology of severe COVID-19 disease and the role of inflammatory cytokines in driving respiratory damage, coagulopathy, end-organ failure, and death, which is idealized in Figure 1. 1,2 We know that 90% of patients with COVID-19 recover, but we are also aware that in about 10% of patients the disease is progressive, and that this is heavily influenced by a growing number of risk factors, including attendant cardiovascular disease, obesity, hypertension, and age. This stage 3 of COVID-19, when the disease may rapidly progress to fatality, has been continuously elucidated and referred to as "cytokine storm," given the presence of elevated levels of inflammatory cytokines and chemokines including interleukin 1 (IL-1), IL-6, tumor necrosis factor (TNF), granulocytemacrophage colony-stimulating factor (GM-CSF), gamma interferon, and monocyte chemotactic protein-1 (MCP-1).…”

Section: ■ Introductionmentioning

confidence: 99%