Neutralizing Anti-interferon-γ Autoantibodies: an Ameliorating Factor in COVID-19 Infection?

Kačar, Mark; Cortes-Acevedo, Paulina; Patel, Vinesh; Carter, Clive; Hughes, Pamela J.; McGann, Hugh; Gkrania‐Klotsas, Effrossyni; Baxendale, Helen; Barcenas-Morales, Gabriela; Döffinger, Rainer; Savic, Sinisa

doi:10.1007/s10875-021-01102-7

Cited by 5 publications

(9 citation statements)

References 21 publications

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“…The importance of type ], indicating a dominant role for IFNa and IFNv for innate immune-mediated protection against SARS-CoV2 infection. Notably, one individual with established neutralizing autoAbs against IFNg, resulting in acquired IFNg deficiency and mycobacterial infection, did not develop pneumonia or other features of severe COVID-19 following SARS-CoV2 infection [44]. This suggests that IFNg, unlike IFNa/v, does not play a significant role in anti-SARS-CoV2 immunity.…”

Section: Andandmentioning

confidence: 96%

“…However, the age of affected IEI patients was lower (median 24 yrs vs 48 yrs; Fig. 1A), and the proportion admitted to ICU was higher (14.0% vs 2–5%) than the general population [12,27–63,67,69–75,76 ▪▪ ]. Within the different classifications of IEIs, SARS-CoV2-infected CVID patients were significantly older (mean: 40.4 years) than SARS-CoV2 + patients with agammaglobulinemia (mean: 23.1 years), chronic granulomatous disease (CGD) (mean: 15.4 years), or APECED (mean: 24.4 years) (Fig.…”

Section: Introductionmentioning

confidence: 97%

“…Examples of this include not only susceptibility to infection by HSV-1 [4], respiratory infections [5,6,8], EBV [7], or attenuated viral vaccines [5,6] in some IEIs, but also the occurrence of enteroviral meningioencephalitis (∼5%) and vaccine-associated poliomyelitis (∼1.5%) in X-linked agammaglobulinemia (XLA) patients [26]. Over the past 12 months, reports of individual cases [27–53] and of individuals with the same type of IEI [54 ▪ ,55–66], as well as local [58,67,68], national [69–75] and international [76 ▪▪ ] cohort studies have assessed the outcomes of SARS-CoV2 infection on such individuals. These studies have provided key findings regarding host defense against SARS-CoV2 infection, and mechanisms of disease pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms underlying host defense and disease pathology in response to severe acute respiratory syndrome (SARS)-CoV2 infection: insights from inborn errors of immunity

Tangye

Bucciol

Meyts

2021

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewThe severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV2)/COVID-19 pandemic has reminded us of the fundamental and nonredundant role played by the innate and adaptive immune systems in host defense against emerging pathogens. The study of rare ‘experiments of nature’ in the setting of inborn errors of immunity (IEI) caused by monogenic germline variants has revealed key insights into the molecular and cellular requirements for immune-mediated protection against infectious diseases. This review will provide an overview of the discoveries obtained from investigating severe COVID-19 in patients with defined IEI or otherwise healthy individuals.Recent findingsGenetic, serological and cohort studies have provided key findings regarding host defense against SARS-CoV2 infection, and mechanisms of disease pathogenesis. Remarkably, the risk factors, severity of disease, and case fatality rate following SARS-CoV2 infection in patients with IEI were not too dissimilar to that observed for the general population. However, the type I interferon (IFN) signaling pathway – activated in innate immune cells in response to viral sensing – is critical for anti-SARS-CoV2 immunity. Indeed, genetic variants or autoAbs affecting type I IFN function account for up to 20% of all cases of life-threatening COVID-19.SummaryThe analysis of rare cases of severe COVID-19, coupled with assessing the impact of SARS-CoV2 infection in individuals with previously diagnosed IEI, has revealed fundamental aspects of human immunology, disease pathogenesis and immunopathology in the context of exposure to and infection with a novel pathogen. These findings can be leveraged to improve therapies for treating for emerging and established infectious diseases.

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Section: Andandmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Mechanisms underlying host defense and disease pathology in response to severe acute respiratory syndrome (SARS)-CoV2 infection: insights from inborn errors of immunity

Tangye

Bucciol

Meyts

2021

Current Opinion in Allergy &Amp; Clinical Immunology

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“…A patient with endogenous anti-IFNγ antibodies was treated for COVID-19 with plasma exchange and exogenous IFNγ, but interestingly he did not have severe COVID-19 symptoms. 10 HLA-DR expression may be useful as a biomarker to define an endotype that benefits from IFNγ, as IFNγ restored monocyte activation and improved ventilator-associated pneumonia in otherwise immunocompetent COVID-19 patients with decreased monocyte HLA-DR 11 . However, as one would predict from the U-shaped biology of IFNγ ( Figure 1 A), studies are conflicting in terms of whether greater IFNγ production is associated with worsened outcomes in severe COVID-19.…”

Section: Main Textmentioning

confidence: 99%

Interferon gamma runs interference on persistent COVID-19

Elliott

Wang

2021

Med

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“…Some publications point to IFN-'s protective role in antiviral protection as well as the efficacy of IFN-preparations in the treatment of this condition [264]. Other studies link elevated IFN levels in the blood with the severity of COVID-19 patients' symptoms [265], as well as the ineffectiveness of IFN in antiviral protection of airway epithelial cells and its potential to induce ACE2 expression on intestinal epithelial cells [266]. The i1 factors promote the utilization of already infected epithelial cells but only weakly prevent their infection with SARS-CoV-2, which appears to be limiting the antiviral benefits of the i1 response in COVID-19.…”

mentioning

confidence: 99%

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

Gusev

Sarapultsev

Соломатина

et al. 2022

IJMS

164

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The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus’s protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2’s ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection.

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Neutralizing Anti-interferon-γ Autoantibodies: an Ameliorating Factor in COVID-19 Infection?

Cited by 5 publications

References 21 publications

Mechanisms underlying host defense and disease pathology in response to severe acute respiratory syndrome (SARS)-CoV2 infection: insights from inborn errors of immunity

Mechanisms underlying host defense and disease pathology in response to severe acute respiratory syndrome (SARS)-CoV2 infection: insights from inborn errors of immunity

Interferon gamma runs interference on persistent COVID-19

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

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