In a recent study published in the Journal of Interferon & Cytokine Research, researchers compared the cytokine storms of pandemic flu and coronavirus 2 (SARS-CoV-2) infections of severe acute respiratory syndrome.
Study: Comparison of COVID-19 cytokine storms and pandemic influenza. Image Credit: NIAID
Fund
Emerging respiratory viruses pose a serious health risk because they have the potential to create large-scale outbreaks. The SARS-CoV-2 pandemic has caused millions of cases of serious infection and fatalities worldwide in the last two years. Vaccination against coronavirus disease 2019 (COVID-19) and natural infection has been shown to provide protective immune responses against SARS-CoV-2, but the parameters that affect morbidity are not well understood.
Matching the immune fingerprints of SARS-CoV-2 infections with those of other serious respiratory infections, such as pandemic flu, could help resolve current debates about the reasons for their serious manifestations. As a result, finding similarities in the immunopathology of two diseases could lead to immunotherapy goals addressing shared pathogenic processes. Meanwhile, identifying different traits that distinguish each infection can lead to the discovery of specific immune modifications that aid in the development of diagnostic and personalized therapies for each case.
About the study
In the current study, researchers summarize the immunopathological elements of pandemic influenza and COVID-19, considering cytokine storms as the underlying cause of morbidity. The team looked at differences and similarities in the cytokine signatures of both infections to identify more attractive compounds for the development of translational drugs and medications.
This review examines the cytokine storm syndromes (CSS) observed during influenza and COVID-19 to identify the conserved immunopathogenic processes that underlie the serious disease. In addition, the researchers provide the theoretical basis for future studies on particular cytokine systems involved in the pathogenesis of COVID-19 by emphasizing different immune features in severe SARS-CoV-2 infection, presenting potential immunotherapy goals.
Mechanisms behind the sepsis cytokine storm. Sepsis is an exaggerated immune reaction caused by a local or systemic infection. People with this condition show high levels of cytokines in the circulation (hypercytokinemia), a phenomenon called “cytokine storm”. The mechanisms that drive the progression of a normal immune response against a pathogen to sepsis are being investigated. The clinical and demographic characteristics of affected individuals, together with genetic factors that promote excessive immune activation or that affect the regulatory mechanisms of the immune system, may contribute to the pathobiology of sepsis. Lush cytokine production causes harmful effects on local cells, activation and increased endothelial permeability and microthrombosis. Hyperkytokinemia is also accompanied by many anti-inflammatory mechanisms that inhibit the functions of immune cells (immunoparalysis). Taken together, these alterations (cytokine storm + immunoparalysis) lead to the development of an organic insufficiency without eliminating the infection. Understanding the pathogenesis of sepsis is crucial to addressing other serious infections such as COVID-19 and pandemic influenza. The artwork used in this figure was modified from Biorender (Creative Commons Attribution 3.0 Unported License. COVID-19, coronavirus disease 2019.
Results and conclusions
Overall, the data reported in this article illustrate significant differences and similarities in the COVID-19 immune signature and severe influenza. In addition, both diseases increase cytokine levels 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 characteristics. in severe SARS. -CoV-2 and influenza infections. In addition, IL-10 has regulatory functions and fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) have angiogenic properties. In addition, cytokines such as chemokine ligand 8 (motif CXC) (CXCL8), CXCL10, CXCL9, chemokine ligand 2 (motif CC) (CCL2), CCL5, and CCL4 contain chemoattractant traits. In addition, granulocyte colony stimulating factor (G-CSF), PDGF, and FGF exhibit growth factor characteristics.
Therefore, the authors noted that pathogenic processes such as increased innate immune stimulation, microvascular dysfunction, and monocyte or neutrophil chemotaxis may be relevant during COVID-19 and influenza diseases. Using the information presented in this review, it is possible to conclude that the CSS of severe COVID-19 and influenza was similar, implying comparable pathogenic pathways that could be exploited for therapeutic applications.
Undoubtedly, both viruses were recognized by identical pattern recognition receptors (PRRs), activate similar signaling pathways, and need comparable adaptive and innate immune elements for their protection. Elevated inflammatory cytokines and PRRs, including IL-1, TNF, and IL-6, were observed in COVID-19 CS and severe influenza, suggesting a chronic innate inflammatory cascade that was detrimental to the host. Hypothetically, addressing these compounds could reduce their important immune and vascular impacts on the pathophysiology of sepsis, relaxing inflammation, and allowing extrapulmonary organs and lungs to restore balance.
The cytokine storm profiles of pandemic influenza and COVID-19. (A) Frequently or differentiated high cytokines, chemokines, and growth factors during severe influenza and COVID-19 were identified by retrospective analysis of independent studies. (B) Immune profiles distinguishing influenza from COVID-19 identified by parallel comparisons. The artwork used in this figure was modified from Biorender (Creative Commons Attribution 3.0 Unported License).
In contrast, there was a disparity in the immune footprint of COVID-19 and influenza. Increased levels of auxiliary cytokines type 1 T (Th1) plus IL-2, a proliferation-inducing ligand (APRIL), soluble tumor necrosis factor 2 receptor (sTNF-R2), sTNF-R1, CXCL17, and surfactant protein D (SP-). D) in patients with severe influenza. In addition, severe patients with SARS-CoV-2 show a Th2 / Th1 / Th17 polyfunctional immune activation pattern. According to the findings, SARS-CoV-2, not the flu virus, caused a multifunctional and abundant CS profile.
As a result, the restoration of a balanced immune response could be a viable goal for host-directed therapy targeted at some subsets of patients with SARS-CoV-2. The team proposes that optimal immune therapy for COVID-19 should inhibit particular immune signaling pathways linked to hyperinflammation and restore useful immune homeostasis that enhances protective immunity in the subset of patients producing multifunctional cytokines.
The authors stated that further study was needed to confirm these immune characteristics and determine the ideal time to provide specific immunotherapies based on the cytokine dynamics of these diseases (SARS-CoV-2 and influenza infections). They mentioned that future research should assess whether tezepelumab, which improves lung function and reduces exacerbations and eosinophilia in people with uncontrolled asthma, could improve the results of COVID-19.