Could SARS-CoV-2-Induced Hyperinflammation Magnify the Severity of Coronavirus Disease (CoViD-19) Leading to Acute Respiratory Distress Syndrome?

Girija, A. S. Smiline; Shankar, Esaki Muthu; Larsson, Marie

doi:10.3389/fimmu.2020.01206

Cited by 310 publications

(104 citation statements)

References 33 publications

(36 reference statements)

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“…In addition, cytokine levels are also reported to be indicative of extrapulmonary multiple-organ failure (42,43). Reports suggest that upregulation of IL-6, IL-8, and TNF-α contributes to SARS-related ARDS (35,44). Interestingly, while we did observe the upregulation of TNF-α, IL-6 levels remained unchanged.…”

Section: Discussioncontrasting

confidence: 49%

K18-hACE2 mice develop respiratory disease resembling severe COVID-19

Yinda

Port

Bushmaker

et al. 2020

Preprint

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SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 [hACE2]) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 104 TCID50 or 105 TCID50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 105 TCID50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Taken together, this suggests that this mouse model can be useful for studies of pathogenesis and medical countermeasure development.

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Section: Discussioncontrasting

confidence: 49%

K18-hACE2 mice develop respiratory disease resembling severe COVID-19

Yinda

Port

Bushmaker

et al. 2020

Preprint

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“…This leads to the deposition of anaphylatoxins such as C5a that serve as chemo attractants for other inflammatory cells such as monocytes, neutrophils, and eosinophils through the secretion of diverse inflammatory cytokines and chemokines [123,124]. This partly contributes to the ongoing cytokine storm as the excessive unchecked production of cytokines such as IL-6, IL-10, GMCSF, IL-1β, and TNF-α ensues [125,126]. This uncontrolled release of inflammatory cytokines results in both local and systemic pathology.…”

Section: Immune Evasion and Subsequent Disease Pathogenesismentioning

confidence: 99%

Immuno-epidemiology and pathophysiology of coronavirus disease 2019 (COVID-19)

et al. 2020

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Occasional zoonotic viral attacks on immunologically naive populations result in massive death tolls that are capable of threatening human survival. Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent that causes coronavirus disease (COVID-19), has spread from its epicenter in Wuhan China to all parts of the globe. Real-time mapping of new infections across the globe has revealed that variable transmission patterns and pathogenicity are associated with differences in SARS-CoV-2 lineages, clades, and strains. Thus, we reviewed how changes in the SARS-CoV-2 genome and its structural architecture affect viral replication, immune evasion, and transmission within different human populations. We also looked at which immune dominant regions of SARS-CoV-2 and other coronaviruses are recognized by Major Histocompatibility Complex (MHC)/Human Leukocyte Antigens (HLA) genes and how this could impact on subsequent disease pathogenesis. Efforts were also placed on understanding immunological changes that occur when exposed individuals either remain asymptomatic or fail to control the virus and later develop systemic complications. Published autopsy studies that reveal alterations in the lung immune microenvironment, morphological, and pathological changes are also explored within the context of the review. Understanding the true correlates of protection and determining how constant virus evolution impacts on host-pathogen interactions could help identify which populations are at high risk and later inform future vaccine and therapeutic interventions.

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“…9 Taking this a step further, severely infected patients with ARDS have elevated serum levels of IL-1B, IL1RA, IL-6, IL-7, IL-8, IL-17, IL-9, IL-10, fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFNγ), granulocyte colony-stimulating factor (G-CSF), interferonγ-inducible protein (IP10), monocyte chemoattractant protein (MCP1), macrophage inflammatory protein-1α (MIP1α), platelet-derived growth factor (PDGF), tumor necrosis factor (TNFα), and vascular endothelial growth factor (VEGF) ( Table 1). 9,[14][15][16][17] Because there is no specific antiviral therapy for COVID-19, understanding of the cytokine storm mechanisms in this disease could help to reveal possible therapeutic interventions. Therefore, among several inflammatory cells and cytokines, T-helper (Th)-17 cells are a unique subset of a cluster of differentiation 4 (CD4 + ) T-helper cells characterized by the production of pro-inflammatory cytokines such as IL-17A, IL-17F, and IL-22.…”

Section: Introductionmentioning

confidence: 99%

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

Shibabaw¹

2020

JIR

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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.

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Could SARS-CoV-2-Induced Hyperinflammation Magnify the Severity of Coronavirus Disease (CoViD-19) Leading to Acute Respiratory Distress Syndrome?

Cited by 310 publications

References 33 publications

K18-hACE2 mice develop respiratory disease resembling severe COVID-19

K18-hACE2 mice develop respiratory disease resembling severe COVID-19

Immuno-epidemiology and pathophysiology of coronavirus disease 2019 (COVID-19)

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

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