How COVID-19 induces cytokine storm with high mortality

Hojyo, Shintaro; Uchida, M.; Tanaka, Kumiko; Hasebe, Rie; Tanaka, Yuki; Murakami, Masaaki; Hirano, Toshio

doi:10.1186/s41232-020-00146-3

Cited by 536 publications

(517 citation statements)

References 79 publications

(119 reference statements)

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“…This response further attracts more cells like natural killer cells, T-lymphocytes, bloodborne macrophages, and neutrophils which infiltrate from the blood into the alveoli and aggravate the inflammatory response as shown in Figure 2 . Interestingly, STAT3 also is known to contribute to the cytokine storm via co-activation of IL-6 amplifier that enhances cytokine production [ 9 ]. The COVID −19 patients have been reported to present with high levels of pro-inflammatory cytokines like IL-6 and these levels have been attributed to the severity of the disease [ 10 ].…”

Section: Stakeholders Of Sars-cov-2 Mediated Inflammation and Its Marmentioning

confidence: 99%

“…The JAK/STAT signaling components like JAK1-3 and STAT1-6 have been associated with various roles in immune responses like IL-2, IL-4, IL-6, IL-12 signaling, Th (T-helper)1, Th2, Treg cell and Th9, Th 17 cell differentiation, the proliferation of viral selective CD8+ T cells and B-cell lymphoma 2 (Bcl-2) [ 2 , 56 ]. It is evident that cytokines are necessary for combating viral infections but the hyperinflammatory conditions created by SARS-CoV-2 infection due to cytokine storm could lead to conditions like ARDS and even death [ 9 ]. To prevent this, the inhibition of the JAK/STAT pathway may look to be a promising strategy but having said that, prolonged inhibition of this pathway could lead to compromised immune responses in the body that could promote the proliferation of the SARS-CoV-2.…”

Section: Role Of Jak/stat Signaling Pathway In the Immune Systemmentioning

confidence: 99%

See 1 more Smart Citation

JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

Satarker

Tom²,

Shaji³

et al. 2020

Postgraduate Medicine

120

109

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As the incidence of COVID-19 increases with time, more and more efforts are made to pave a way out for the therapeutic strategies to deal with the disease progression. Inflammation being a significant influencer has implicated us to re-look into its signaling cascades drawing attention towards the JAK/STAT pathway. Considered as a major signaling mediator of cytokines and chemokines, the JAK/STAT pathway has significantly contributed to the worsening of COVID-19. JAK phosphorylation mediated by cytokine receptor activation leads to phosphorylation of STATs that translocate into the nucleus to translate for inflammatory mediators. The SARS-CoV-2 infection triggers the inflammation via the JAK/STAT pathway mainly through its structural and non-structural proteins leading towards the development of cytokine storms. This produces various inflammatory markers in the host that determine the disease severity. Therefore, inhibiting JAK/STAT signaling with JAK/STAT inhibitors like Ruxolitinib, Baricitinib, Tofacitinib could hamper the inflammatory cascade and reduce inflammation. Even though they are implicated with multiple adverse effects, the regulatory authorities have supported its use, and numerous clinical trials are in progress to prove their safety and efficacy. On the contrary, the exact mechanism of JAK/STAT inhibition at molecular levels remains to be speculative for which further investigations are required.

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Section: Stakeholders Of Sars-cov-2 Mediated Inflammation and Its Marmentioning

confidence: 99%

Section: Role Of Jak/stat Signaling Pathway In the Immune Systemmentioning

confidence: 99%

JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

Satarker

Tom²,

Shaji³

et al. 2020

Postgraduate Medicine

120

109

View full text Add to dashboard Cite

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“…Furthermore, the induction of the EETs by this particular fungus culminates in an ROS-independent process [174]. Altogether, this indicates that eosinophils likely play an important role in the immune responses to A. fumigatus and their dysregulation may lead to increased morbidity associated with the primary infection [92].…”

Section: Eosinophils and Their Traps In Infectious Diseasesmentioning

confidence: 95%

“…Rapidly, this novel virus known as SARS-CoV-2 emerged and it has spread worldwide causing a great pandemic during 2020. Since this pandemic started, many efforts have tried to characterize the pathology and immune responses to this novel coronavirus and a particular feature is the hyperreactive uncontrolled immune response that leads to the detriment of the patient's health [92][93][94].…”

Section: Nets and Covid-19mentioning

confidence: 99%

“NETs and EETs, a Whole Web of Mess”

et al. 2020

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Neutrophils and eosinophils are granulocytes that have very distinct functions. Neutrophils are first responders to external threats, and they use different mechanisms to control pathogens. Phagocytosis, reactive oxygen species, and neutrophil extracellular traps (NETs) are some of the mechanisms that neutrophils utilize to fight pathogens. Although there is some controversy as to whether NETs are in fact beneficial or detrimental to the host, it mainly depends on the biological context. NETs can contribute to disease pathogenesis in certain types of diseases, while they are also undeniably critical components of the innate immune response. On the contrary, the role of eosinophils during host immune responses remains to be better elucidated. Eosinophils play an important role during helminthic infections and allergic responses. Eosinophils can function as effector cells in viral respiratory infections, gut bacterial infections, and as modulators of immune responses by driving the balance between Th1 and Th2 responses. In particular, eosinophils have biological activities that appear to be quite similar to those of neutrophils. Both possess bactericidal activity, can activate proinflammatory responses, can modulate adaptive immune responses, can form extracellular traps, and can be beneficial or detrimental to the host according to the underlying pathology. In this review we compare these two cell types with a focus on highlighting their numerous similarities related to extracellular traps.

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“…These studies indicate that the effect of SARS-CoV-2 on the brain may be a critical part of the COVID-19 pathobiology, and neurological manifestations should be carefully monitored in COVID-19 patients. Activation of systemic inflammatory responses via an acute increase in proinflammatory cytokines, including interleukin-6 (IL-6) termed as Cytokine Storm, has been linked to disease severity and death in COVID-19 patients (Hashizume, 2020;Hojyo et al, 2020;Lukan, 2020). IL-6 like pro-inflammatory interleukins are also elevated in some neurodegenerative diseases such as Parkinson's disease (PD) (Kwiatek-Majkusiak et al, 2020), suggesting that patients with neurodegenerative diseases may be more susceptible to the severity of COVID-19.…”

Section: Neurological Manifestations In Coronavirus Disease 2019mentioning

confidence: 99%

Neuronal and Cerebrovascular Complications in Coronavirus Disease 2019

Andrabi

2020

Front. Pharmacol.

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Coronavirus disease 2019 (COVID-19) is a pandemic disease resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, primarily in the respiratory tract. This pandemic disease has affected the entire world, and the pathobiology of this disease is not yet completely known. The Interactions of SARS-CoV-2 proteins with different cellular components in the host cell may be necessary for understanding the disease mechanism and identifying crucial pharmacological targets in COVID-19. Studies have suggested that the effect of SARS-CoV-2 on other organs, including the brain, maybe critical for understanding the pathobiology of COVID-19. Symptoms in COVID-19 patients, including impaired consciousness dizziness, headache, loss of taste and smell, vision problems, and neuromuscular pain, suggest that neuronal complications comprise a crucial component of COVID-19 pathobiology. A growing body of literature indicates that SARS-CoV-2 can enter the brain, leading to neuronal defects in COVID-19 patients. Other studies suggest that SARS-CoV-2 may aggravate neuronal complications due to its effects on the cerebrovascular system. Emerging pieces of evidence show that stroke can be one of the leading neurological complications in COVID-19. In this review, we describe the observations about neuronal complications of COVID-19 and how SARS-CoV-2 may invade the brain. We will also discuss the cerebrovascular problems and occurrence of stroke in COVID-19 patients. We will also present the observations and our views about the potential pharmacological strategies and targets in COVID-19. We hope this review will help comprehend the current knowledge of neuronal and cerebrovascular complications from SARS-CoV-2 infections and highlight the possible long-term consequences of SARS-CoV-2 on the human brain.

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How COVID-19 induces cytokine storm with high mortality

Cited by 536 publications

References 79 publications

JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy

“NETs and EETs, a Whole Web of Mess”

Neuronal and Cerebrovascular Complications in Coronavirus Disease 2019

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