IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection

Gadotti, Ana Carolina; Deus, Marina de Castro; Telles, João Paulo; Wind, Rafael; Goes, Marina; Ossoski, Roberta Garcia Charello; Padua, Alessandra Michalski de; Noronha, Lúcia de; Moreno-Amaral, Andréa Novais; Baena, Cristina Pellegrino; Tuon, Felipe Francisco

doi:10.1016/j.virusres.2020.198171

Cited by 170 publications

(176 citation statements)

References 28 publications

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“…Patients presented higher serum leukocyte cell count (p < 0.001), CRP level (p = 0.01), and length of stay (p < 0.001). Our group also demonstrated previously that these patients exhibit elevated levels of tumor necrosis factor-alpha, interleukin-4, interleukin-6, and interferon-gamma [ 36 ]. The inflammatory pattern response is still under investigation; however, it seems that the innate immune response contributes to the disease severity [ 35 ].…”

Section: Discussionsupporting

confidence: 71%

Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease

Gadotti

Lipiński

Vasconcellos

et al. 2021

Free Radical Biology and Medicine

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Section: Discussionsupporting

confidence: 71%

Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease

Gadotti

Lipiński

Vasconcellos

et al. 2021

Free Radical Biology and Medicine

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“…These include SARS-CoV-2 mediated apoptosis; IFN-γ signaling pathway and proteasomal degradation of CD4 pathway playing an important role in viral pathogenesis. Various clinical reports show elevated blood levels of IFN-γ, associated with higher degree of SARS-CoV-2 pathogenesis (Gadotti et al., 2020 ). The degree centrality analysis of IFN-γ signaling suggests that IRF1/9 and IRF7 are the key players of this pathway.…”

Section: Discussionmentioning

confidence: 99%

Structural similarity-based prediction of host factors associated with SARS-CoV-2 infection and pathogenesis

Tiwari

Mishra

Gupta

et al. 2021

Journal of Biomolecular Structure and Dynamics

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The current pandemic resulted from SARS-CoV-2 still remains as the major public health concern globally. The precise mechanism of viral pathogenesis is not fully understood, which remains a major hurdle for medical intervention. Here we generated an interactome profile of protein-protein interactions based on host and viral protein structural similarities information. Further computational biological study combined with Gene enrichment analysis predicted key enriched pathways associated with viral pathogenesis. The results show that axon guidance, membrane trafficking, vesicle-mediated transport, apoptosis, clathrin-mediated endocytosis, Vpu mediated degradation of CD4 T cell, and interferon-gamma signaling are key events associated in SARS-CoV-2 life cycle. Further, degree centrality analysis reveals that IRF1/9/7, TP53, and CASP3, UBA52, and UBC are vital proteins for IFN-γ-mediated signaling, apoptosis, and proteasomal degradation of CD4, respectively. We crafted chronological events of the virus life cycle. The SARS-CoV-2 enters through clathrin-mediated endocytosis, and the genome is trafficked to the early endosomes in a RAB5-dependent manner. It is predicted to replicate in a double-membrane vesicle (DMV) composed of the endoplasmic reticulum, autophagosome, and ERAD machinery. The SARS-CoV-2 down-regulates host translational machinery by interacting with protein kinase R, PKR-like endoplasmic reticulum kinase, and heme-regulated inhibitor and can phosphorylate eIF2a. The virion assembly occurs in the ER-Golgi intermediate compartment (ERGIC) organized by the spike and matrix protein. Collectively, we have established a spatial link between viral entry, RNA synthesis, assembly, pathogenesis, and their associated diverse host factors, those could pave the way for therapeutic intervention.

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“…Collapsing focal segmental glomerulosclerosis (FSGS) has been associated to therapeutic use of IFN-α, -β, and -γ [ 72 ]. Considering the robust interferon response in patients with COVID-19 at certain stages of the disease [ 73 , 74 ], it is then possible that IFN may be inducing podocyte injury in these patients.…”

Section: Clinical Characteristics Of Cov-akimentioning

confidence: 99%

COVID-19 and the Kidney: A Worrisome Scenario of Acute and Chronic Consequences

Sanchez-Russo

Billah

Chancay

et al. 2021

JCM

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Acute kidney injury (AKI) is a common finding in patients with coronavirus disease 2019 (COVID-19) and has been associated with higher rates of death when compared to COVID-19 patients without kidney injury. Whereas the definitive pathogenesis of COVID-19-related AKI (CoV-AKI) is not clear, histopathologic evidence seems to point at multiple etiologies for the disease, including indirect and direct viral kidney injury. The high incidence of CoV-AKI, along with the aggressive clinical presentation of this entity, have increased the demands for kidney replacement therapies, rapidly overwhelming the supplies of healthcare systems even in major tertiary care centers. As a result, nephrologists have come up with alternatives to maximize the efficiency of treatments and have developed non-conventional therapeutic alternatives such as the implementation of acute peritoneal dialysis for critically ill patients. The long-term implications of CoV-AKI are yet unknown, though early studies suggest that around one third of the patients who survive will remain dependent on kidney replacement therapy. Nephrologists and healthcare workers need to be familiar with the clinical presentation and therapeutic challenges of CoV-AKI in order to develop strategies to mitigate the burden of the disease for patients, and for services providing kidney replacement therapies.

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IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection

Cited by 170 publications

References 28 publications

Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease

Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease

Structural similarity-based prediction of host factors associated with SARS-CoV-2 infection and pathogenesis

COVID-19 and the Kidney: A Worrisome Scenario of Acute and Chronic Consequences

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