Study: Comparison of COVID-19 cytokine storms and pandemic influenza. Image credit: NIAID
Record
Emerging respiratory viruses pose a serious health risk because they have the potential to cause large-scale outbreaks. The SARS-CoV-2 pandemic has led to millions of serious cases of infection and death worldwide in the last two years. Vaccination against Coronavirus 2019 (COVID-19) and natural infection have been shown to provide protective immune responses to SARS-CoV-2, but the parameters affecting morbidity are not well understood. Matching the fingerprints of the immune system of SARS-CoV-2 infections with those of other serious respiratory infections, such as pandemic influenza, could help settle the current debate about the reasons behind their serious manifestations. As a result, finding similarities in the immunopathology of two diseases could lead to immunotherapy goals that address common pathogenic processes. Meanwhile, identifying distinct features that distinguish each infection can lead to the discovery of specific immune modifications that help develop diagnostic and individualized treatments for each case.
About the study
In the current study, researchers summarized the immunopathological features of pandemic influenza and COVID-19, looking at cytokine storms as the underlying cause of morbidity. The team analyzed differences and similarities in the cytokine signatures of both infections to identify compounds more attractive for the development of translational drugs and drugs. This review examines the Cytokine Storm Syndromes (CSS) observed during influenza and COVID-19 to identify persistent immunopathogenic processes that support serious disease. In addition, the researchers provide the theoretical basis for a future study of specific cytokine systems involved in the pathogenesis of COVID-19, highlighting distinct immune features in severe SARS-CoV-2 infection, presenting potential immunotherapy targets. Mechanisms behind the cytokine storm of sepsis. Sepsis is an excessive immune response caused by a local or systemic infection. People with this condition have elevated levels of circulating cytokines (hypercellular anemia), a phenomenon called the “cytokine storm.” The mechanisms that drive the progression from a normal immune response to a sepsis pathogen are under investigation. The clinical and demographic characteristics of the affected individuals, together with genetic factors that promote overactive immune system or influence the regulatory mechanisms of the immune system, may contribute to the pathobiology of sepsis. Excessive cytokine production leads to detrimental effects on local cells, activation and increased endothelial permeability and microthrombosis. Hypercytocytemia is also accompanied by many anti-inflammatory mechanisms that disrupt the functions of immune cells (immunoprolysis). Together, these lesions (cytokine storm + immunosuppression) result in the development of organ failure without clearing the infection. Understanding the pathogenesis of sepsis is vital in approaching other serious infections such as COVID-19 and pandemic influenza. The artwork used in this image has been modified by Biorender (Creative Commons Attribution 3.0 Unported License. COVID-19, coronavirus 2019.
Results and conclusions
Overall, the data presented in this article show significant differences and similarities in the immune signature of severe COVID-19 and influenza. In addition, both diseases increase cytokine levels with a variety of 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-2 and influenza infections. In addition, IL-10 has regulatory functions and both fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) have angiogenic properties. In addition, cytokines such as the chemokine linker (pattern CXC) 8 (CXCL8), CXCL10, CXCL9, the chemokine linker (pattern CC) 2 (CCL2), CCL5, and CCL4 have chemotactive properties. In addition, granulocyte colony stimulating factor (G-CSF), PDGF and FGF exhibit growth factor characteristics. Therefore, the authors note that pathogenic processes such as increased innate immune stimulation, microvascular dysfunction, and monocyte or neutrophil chemotaxis may be relevant during COVID-19 disease and influenza. Using the information presented in this review, it is possible to conclude that the CSS of severe COVID-19 and influenza was similar, suggesting comparable pathogens that could be utilized for therapeutic applications. Of course, both viruses have been identified by the same pattern recognition receptors (PRRs), activate similar signaling pathways, and require comparable adaptive and innate immune components for protection. Elevated cytokines induced by inflammation and PRR, including IL-1, TNF, and IL-6, were observed in the CS of severe COVID-19 and influenza, suggesting a chronic congenital inflammatory cataract that was harmful to the host. Hypothetically, treatment of these compounds can reduce their immune and vascular effects, important in the pathophysiology of sepsis, relieving inflammation and allowing the extrapulmonary organs and lungs to regain balance. The cytokine storm profiles of pandemic influenza and COVID-19. (ONE) Cytokines, chemokines, and growth factors usually or differentially elevated during severe influenza and COVID-19 were identified by retrospective analysis of independent studies. (SI) The immune profiles that distinguish influenza from COVID-19 are determined by parallel comparisons. The artwork used in this format has been modified by Biorender (under a Creative Commons Attribution 3.0 Unported License. In contrast, there was a difference in the immune footprint of COVID-19 and influenza. Elevated levels of helper cytokines of type 1 T (Th1) plus IL-2, proliferative ligand (APRIL), soluble tumor necrosis factor 2 receptor (sTNF-R2), sTNF-R1, CXCL17 and surfactant protein D (SP-D) patients with severe influenza. In addition, patients with severe SARS-CoV-2 exhibit a multifunctional Th2 / Th1 / Th17 immunoactivation pattern. According to the findings, SARS-CoV-2, not the flu virus, caused a multifunctional and abundant CS profile. As a result, restoring a balanced immune response could be a viable target for host-directed therapy targeting certain subsets of SARS-CoV-2 patients. The team suggests that optimal immunotherapies for COVID-19 should inhibit specific immune signaling pathways associated with hyperinflammation and restore beneficial immune homeostasis that enhances protective immunity in the subset of multifunctional patients. The authors stated that more study was needed to confirm these immune characteristics and to determine the ideal time to provide specific immunotherapies based on the cytokine dynamics of these diseases (SARS-CoV-2 and influenza infections). They said future research should evaluate whether tezepelumab, which improves lung function and reduces exacerbations and eosinophilia in people with uncontrolled asthma, could improve COVID-19 results.
