A Role of Variance in Interferon Genes to Disease Severity in COVID-19 Patients

Gozman, Leonid; Perry, Kellie; Nikogosov, Dimitri A.; Klabukov, Ilya; Shevlyakov, Artem; Baranova, Ancha

doi:10.3389/fgene.2021.709388

Cited by 10 publications

(11 citation statements)

References 111 publications

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“…Immune responses in COVID-19 patients of various disease severities have been studied (Lega, Naviglio et al 2020, Chiale, Greene et al 2022, Dadras, Afsahi et al 2022). In general, broad induction of IFN responses and antiviral genes are associated with milder/moderate COVID-19, whereas severe COVID-19 is often characterized by a blunt early IFN responses and elevated proinflammatory cytokine expression in nasopharyngeal mucosa (Kwon, Kim et al 2020, Liu, Li et al 2020, Gozman, Perry et al 2021, Janssen, Grondman et al 2021, Vanderbeke, Van Mol et al 2021). Investigation of how IFN responses are induced by SARS-CoV-2 infection, especially early IFN stimulation in some patients, requires further study.…”

Section: Introductionmentioning

confidence: 99%

Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection

Zhou

Gilliam

et al. 2022

Preprint

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Defective viral genomes (DVGs) have been identified in many RNA viruses as a major factor influencing antiviral immune response and viral pathogenesis. However, the generation and function of DVGs in SARS-CoV-2 infection are less known. In this study, we elucidated DVG generation in SARS-CoV-2 and its relationship with host antiviral immune response. We observed DVGs ubiquitously from RNA-seq datasets of in vitro infections and autopsy lung tissues of COVID-19 patients. Four genomic hotspots were identified for DVG recombination and RNA secondary structures were suggested to mediate DVG formation. Functionally, bulk and single cell RNA-seq analysis indicated the IFN stimulation of SARS-CoV-2 DVGs. We further applied our criteria to the NGS dataset from a published cohort study and observed significantly higher DVG amount and frequency in symptomatic patients than that in asymptomatic patients. Finally, we observed unusually high DVG frequency in one immunosuppressive patient up to 140 days after admitted to hospital due to COVID-19, first-time suggesting an association between DVGs and persistent viral infections in SARS-CoV-2. Together, our findings strongly suggest a critical role of DVGs in modulating host IFN responses and symptom development, calling for further inquiry into the mechanisms of DVG generation and how DVGs modulate host responses and infection outcome during SARS-CoV-2 infection.

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Section: Introductionmentioning

confidence: 99%

Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection

Zhou

Gilliam

et al. 2022

Preprint

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“…Several authors have demonstrated that common and rare genetic variants that influence the IFN signaling pathways affect the tendency to develop severe COVID-19. Although the prevalence of the impact is 1–5% in young people (≤60 years of age), this fact should be taken into consideration in elderly people [ 109 , 110 ].…”

Section: Immunosenescence and Inflammaging In The Older Adultsmentioning

confidence: 99%

COVID-19: A Comprehensive Review on Cardiovascular Alterations, Immunity, and Therapeutics in Older Adults

Rivera‐Torres

Girón

José

2023

JCM

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Here, we present a review focusing on three relevant issues related to COVID-19 and its impact in older adults (60 years and older). SARS-CoV-2 infection starts in the respiratory system, but the development of systemic diseases accompanied by severe clinical manifestations has also been reported, with cardiovascular and immune system dysfunction being the major ones. Additionally, the presence of comorbidities and aging represent major risk factors for the severity and poor prognosis of the disease. Since aging-associated decline has been largely related to immune and cardiovascular alterations, we sought to investigate the consequences and the underlying mechanisms of these pathologies to understand the severity of the illness in this population. Understanding the effects of COVID-19 on both systems should translate into comprehensive and improved medical care for elderly COVID-19 patients, preventing cardiovascular as well as immunological alterations in this population. Approved therapies that contribute to the improvement of symptoms and a reduction in mortality, as well as new therapies in development, constitute an approach to managing these disorders. Among them, we describe antivirals, cytokine antagonists, cytokine signaling pathway inhibitors, and vaccines.

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“…Ramensky et al (2021) discussed targeted sequencing of a set of clinically important genes associated with cardiovascular diseases. Gozman et al (2021) raised important actual problem of the role of genetic variance in disease severity in COVID-19 Patients. This problem is continuing to be actively discussed (Lu et al, 2021).…”

Section: Liu Et Al Consider How Cutaneous Melanoma Involves Erbb Tyrosine Kinase Family Members (Erbb Receptor Family) In Its Progressionmentioning

confidence: 99%

“… Gozman et al (2021) raised important actual problem of the role of genetic variance in disease severity in COVID-19 Patients. This problem is continuing to be actively discussed ( Lu et al, 2021 ).…”

mentioning

confidence: 99%