“…63 Interestingly, the structural SARS-CoV-2 N protein has also been shown to antagonize IFN signaling by suppressing phosphorylation and translocation of STAT1 and STAT2, representing a potential viral mechanism to evade the innate immune response. 64 GATA2 deficiency, a pleiotropic syndromic disorder, is also associated with increased susceptibility to viral infections, at least partially due to the absence of pDCs in this disorder, a major cell type in producing type I IFN. 65 In agreement with the antiviral role of type I IFN, a case series identified rare missense and nonsense putative loss-of-function (LOF) variants involving TLR7 in D 1 2 0 X X4 young previously healthy males with critical COVID-19; these variants were associated with impaired type I and type II IFN response in these patients.…”
Section: Convergent Immunopathogenic Mechanisms Of Covid-19 and Slementioning
As the world navigates the Coronavirus disease 2019 (COVID-19) pandemic, there is a growing need to assess its impact in patients with autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE). Patients with SLE are a unique population when considering the risk of contracting COVID-19 and infection outcomes. The use of systemic glucocorticoids and immunosuppressants, and underlying organ damage from SLE are potential susceptibility factors. Most patients with SLE have evidence of high type I IFN activity, which may theoretically act as an antiviral line of defense or contribute to the development of a deleterious hyperinflammatory response in COVID-19. Other immunopathogenic mechanisms of SLE may overlap with those described in COVID-19, and thus studies in SLE could provide some insight into immune responses occurring in severe cases of the viral infection. We reviewed the literature to date on COVID-19 in patients with SLE and provide an in-depth review of current research in the area, including immune pathway activation, epidemiology, clinical features, outcomes, and the psychosocial impact of the pandemic in those with autoimmune disease.
“…63 Interestingly, the structural SARS-CoV-2 N protein has also been shown to antagonize IFN signaling by suppressing phosphorylation and translocation of STAT1 and STAT2, representing a potential viral mechanism to evade the innate immune response. 64 GATA2 deficiency, a pleiotropic syndromic disorder, is also associated with increased susceptibility to viral infections, at least partially due to the absence of pDCs in this disorder, a major cell type in producing type I IFN. 65 In agreement with the antiviral role of type I IFN, a case series identified rare missense and nonsense putative loss-of-function (LOF) variants involving TLR7 in D 1 2 0 X X4 young previously healthy males with critical COVID-19; these variants were associated with impaired type I and type II IFN response in these patients.…”
Section: Convergent Immunopathogenic Mechanisms Of Covid-19 and Slementioning
As the world navigates the Coronavirus disease 2019 (COVID-19) pandemic, there is a growing need to assess its impact in patients with autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE). Patients with SLE are a unique population when considering the risk of contracting COVID-19 and infection outcomes. The use of systemic glucocorticoids and immunosuppressants, and underlying organ damage from SLE are potential susceptibility factors. Most patients with SLE have evidence of high type I IFN activity, which may theoretically act as an antiviral line of defense or contribute to the development of a deleterious hyperinflammatory response in COVID-19. Other immunopathogenic mechanisms of SLE may overlap with those described in COVID-19, and thus studies in SLE could provide some insight into immune responses occurring in severe cases of the viral infection. We reviewed the literature to date on COVID-19 in patients with SLE and provide an in-depth review of current research in the area, including immune pathway activation, epidemiology, clinical features, outcomes, and the psychosocial impact of the pandemic in those with autoimmune disease.
“…Specifically, it is known to cleave STAT2 and affect the interferon signaling [ 31 , 75 ]. Among the structural proteins of SARS-CoV-2, the N protein has also been shown to inhibit the type 1 IFN pathway mediated inflammatory cascade by preventing the phosphorylation and nuclear passage of STAT 1 and STAT 2 as shown in Figure 3 [ 76 ]. Figure 3.…”
Section: Deciphering the Link Between Sars-cov-2 Proteins And Jak/stamentioning
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.
“…Compared with SARS-CoV, SARS-CoV-2 does not induce an obvious IFN response in infected human lung tissues [ 138 ]. The SARS-CoV-2 N protein may explain this phenomenon because it antagonizes type I IFN signaling by limiting STAT1 and STAT2 phosphorylation [ 139 ] (Fig. 2 ).…”
Section: Implications For Clinical Applicationsmentioning
The coronavirus disease 19 (COVID-19) pandemic poses a serious global threat to human health and the economy. Based on accumulating evidence, its continuous progression involves not only pulmonary injury but also damage to the cardiovascular system due to intertwined pathophysiological risks. As a point of convergence in the pathophysiologic process between COVID-19 and heart failure (HF), cytokine storm induces the progression of COVID-19 in patients presenting pre-existing or new onset myocardial damage and even HF. Cytokine storm, as a trigger of the progression of HF in patients with COVID-19, has become a novel focus to explore therapies for target populations. In this review, we briefly introduce the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and illuminate the mechanism and links among COVID-19, cytokine storm, and HF. Furthermore, we discuss drugs and therapeutic targets for patients with COVID-19 and HF.
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