Comparison of SARS-CoV-2 and influenza cellular storms

In a recent study published in Journal of Interferon and Cytokine ResearchResearchers have compared the cytokine storms of pandemic influenza, SARS-CoV-2 infection, and severe acute respiratory syndrome.

Study: Comparing cellular storms of COVID-19 and pandemic influenza. Image Credit: NIAID

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Emerging respiratory viruses pose serious health risks because they have the potential to spread disease on a large scale. The SARS-CoV-2 pandemic has resulted in millions of severe infections and deaths globally in the past two years. Vaccination against coronavirus disease 2019 (COVID-19) and natural infection have been shown to provide protective immune responses against SARS-CoV-2, but the parameters that influence morbidity are not well understood.

Matching the immune signatures of SARS-CoV-2 infection with that of other acute respiratory infections, such as pandemic influenza, could help settle current debates about the underlying causes of its severe manifestations. As a result, finding similarities in the immunopathology of the two diseases could lead to immunotherapy targets that address co-disease-causing processes. Meanwhile, identifying the hallmarks of each infection may lead to the discovery of specific immune alterations that aid in the development of diagnostic and personalized treatments for each case.

about studying

In the current study, the researchers summarized the immunopathological elements of pandemic influenza and COVID-19, considering cytokine storms to be the primary cause of the disease. The team analyzed differences and similarities in cytokine signatures for both infections to identify the most attractive compounds for translational drugs and drug development.

This review examines the syndromes of cytokine storm (CSS) seen during influenza and COVID-19 to identify the pathogenic processes of conserved immune systems that support severe disease. Furthermore, the researchers provided the theoretical underpinnings for future study on specific cellular systems implicated in the pathogenesis of COVID-19 by emphasizing distinct immune properties in severe SARS-CoV-2 infection, and presenting potential immunotherapy targets.

The mechanisms underlying the cytokine storm of sepsis.  Sepsis is an exaggerated immune reaction caused by a local or systemic infection.  Individuals with this condition show elevated levels of cytokines in the circulatory system (hypercytosis), a phenomenon called The mechanisms underlying the cytokine storm of sepsis. Sepsis is an exaggerated immune reaction caused by a local or systemic infection. Individuals with this condition show elevated levels of cytokines in the circulation (hypercytosis), a phenomenon called a ‘cytokine storm’. The mechanisms driving the evolution from a normal immune response against a pathogen to sepsis are under investigation. Clinical and demographic features of affected individuals, along with genetic factors that promote excessive immune activation or influence the regulatory mechanisms of the immune system, may contribute to the pathobiology of sepsis. Excessive production of cytokines leads to adverse effects on local cells, their activation, increased endothelial permeability, and microcoagulation. Hyperglycemia is also accompanied by several anti-inflammatory mechanisms that suppress the functions of immune cells (immunoassay). Together, these changes (cytokine storm + immunodegradation) lead to the development of organ failure without clearing the infection. Understanding the pathogenesis of sepsis is critical in dealing with other severe infections such as COVID-19 and pandemic influenza. Artifacts used in this format have been modified from Biorender (https://biorender.com/), licensed under a Creative Commons Attribution 3.0 Unported License. COVID-19, coronavirus disease 2019

RESULTS AND CONCLUSIONS

Overall, the data in this article illustrate significant differences and similarities in the immune signature of severe COVID-19 and influenza. In addition, both diseases increase levels of cytokines with different roles.

Elevated cytokines such as interferon-β (IFN-β) and IFN-α have antiviral properties, and tumor necrosis factor-α (TNFα), interleukin 22 (IL-22, and IL-12) have inflammatory properties in severe SARS-CoV. Novel-2 and influenza infection. Furthermore, IL-10 has regulatory functions, and fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) have angiogenesis properties. In addition, cytokines, such as chemokine (CXC motif) ligand 8 (CXCL8), CXCL10, CXCL9, chemokine (CC motif) ligand 2 (CCL2), CCL5 and CCL4 harbor chemoattractive traits. Moreover, granulocyte colony-stimulating factor (G-CSF), PDGF and FGF exhibit growth factor properties.

Hence, the authors note that pathogenic processes such as increased innate immune stimulation, microvascular dysfunction, and chemotactic concentration of monocytes or neutrophils could be relevant during COVID-19 and influenza diseases. Using the information presented in this review, it is possible to conclude that the CSS for acute COVID-19 and influenza were similar, implying comparable pathogenic pathways that can be leveraged for therapeutic applications.

Certainly, both viruses have been recognized by identical pattern recognition receptors (PRRs), activate similar signaling pathways, and require comparable adaptive and innate immune elements for protection. Elevated proinflammatory and PRR-induced cytokines, including IL-1, TNF and IL-6, were seen in the CS of severe COVID-19 and influenza, suggesting a chronic innate inflammatory cascade that was harmful to the host. Theoretically, treating these compounds may reduce their immunological and vascular effects, which are important in the pathophysiology of sepsis, attenuating inflammation and enabling extrapulmonary organs and lungs to rebalance.

Features of the cytokine storm for pandemic influenza and COVID-19.  (a) Cytokines, chemokines, and growth factors that are commonly or differentially elevated during acute influenza and COVID-19 were identified by retrospective analysis of independent studies.  (B) Immunological profiles distinguishing influenza from COVID-19 identified through parallel comparisons.  Artifacts used in this format have been modified from Biorender (https://biorender.com/), licensed under a Creative Commons Attribution 3.0 Unported License.Features of the cytokine storm for pandemic influenza and COVID-19. (a) Cytokines, chemokines, and growth factors that are commonly or differentially elevated during severe influenza and COVID-19 were identified by retrospective analysis of independent studies. (B) Immunological profiles distinguishing influenza from COVID-19 identified by parallel comparisons. Artifacts used in this format have been modified from Biorender (https://biorender.com/), licensed under a Creative Commons Attribution 3.0 Unported License.

Conversely, there was disparity in the immune signature of COVID-19 and influenza. Elevated levels of T helper type 1 (Th1) cytokines in addition to IL-2, a proliferation-inducible ligand (APRIL), soluble tumor necrosis factor receptor 2 (sTNF-R2), sTNF-R1, CXCL17, and surfactant protein D (SP-d) in patients with severe influenza. Besides, severe SARS-CoV-2 patients show a multifunctional Th2/Th1/Th17 immune activation pattern. According to the results, SARS-CoV-2, not influenza virus, elicited an abundant multifunctional CS profile.

As a result, restoring a balanced immune response could be a viable target for host-directed therapy targeting some subgroups of SARS-CoV-2 patients. The team proposes that optimal immunotherapies for COVID-19 should block specific immune signaling pathways associated with excessive inflammation and restore beneficial immune balance that promotes protective immunity in a subset of patients that produce multifunctional cytokines.

The authors stated that further study is needed to confirm these immunological properties and determine the ideal time to introduce specific immunotherapies based on the cytokine dynamics of these diseases (SARS-CoV-2 and influenza infection). They state that future research should evaluate whether tezepelumab, which improves lung function and reduces exacerbations and eosinophilia in people with uncontrolled asthma, can improve COVID-19 outcomes.

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