Effects of IFN‐γ on immune cell kinetics during the resolution of acute lung injury

Mock, Jason R.; Tune, Miriya K; Dial, Catherine F.; Torres-Castillo, J.L.; Hagan, Robert S.; Doerschuk, Claire M.

doi:10.14814/phy2.14368

Cited by 29 publications

(27 citation statements)

References 48 publications

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“…38 In particular, INF-γ enhances the immune-mediated damage contributing to the pathogenesis of acute lung injury (ALI). 39,40 Studies carried out in patients with ARDS identified different phenotypes depending on the biomarkers found in the serum: ARDS patients with high expression of angiopoietin, plasminogen activator inhibitor 1, INF-γ and IL-6 had a poorer outcome and a higher mortality compared to ARDS subjects without inflammatory markers. 41 Among pro-inflammatory cytokines, IL-6 seems to be a pivotal mediator of CRS as it is able to activate directly T cells and enhancing the cytokine storm.…”

Section: Introductionmentioning

confidence: 99%

The amount of cytokine-release defines different shades of Sars-Cov2 infection

Bindoli

Felicetti

Sfriso

et al. 2020

Exp Biol Med (Maywood)

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The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: “mild”,symbolized as a “drizzle” of cytokines, severe as a “storm”, and critical as a “hurricane”. In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a “cytokine-release syndrome”, SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.

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Section: Introductionmentioning

confidence: 99%

The amount of cytokine-release defines different shades of Sars-Cov2 infection

Bindoli

Felicetti

Sfriso

et al. 2020

Exp Biol Med (Maywood)

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“…Regarding the immunopathological effects of LH immune profile, using murine models it has been shown that high IFN-γ levels could affect the kinetics of the resolution of inflammation-induced lung injury as well as thrombus resolution (23, 24), which could be related to long-lasting symptoms of LH associated to pulmonary coagulopathy and immune-mediated tissue damage.…”

Section: Discussionmentioning

confidence: 99%

“…Using a combined heuristic to first classify the Long Haulers (S1>0.4) and second the severe COVID-19 patients (S2>0), we obtained a sensitivity of 97% for Long Haulers with a 100% specificity and a sensitivity of 88% for severe patients with a specificity of 96% ( Figure 4B). Regarding the immunopathological effects of LH immune profile, using murine models it has been shown that high IFN-γ levels could affect the kinetics of the resolution of inflammation-induced lung injury as well as thrombus resolution (23,24), which could be related to long-lasting symptoms of LH associated to pulmonary coagulopathy and immune-mediated tissue damage.…”

Section: Reduced Feature Multi-class Deep Neural Network Classifiersmentioning

confidence: 99%

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

Patterson

Guevara-Coto

Yogendra³

et al. 2020

Preprint

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Individuals with systemic symptoms long after COVID-19 has cleared represent approximately ~10% of all COVID-19 infected individuals. Here we present a bioinformatics approach to predict and model the phases of COVID so that effective treatment strategies can be devised and monitored. We investigated 144 individuals including normal individuals and patients spanning the COVID-19 disease continuum. We collected plasma and isolated PBMCs from 29 normal individuals, 26 individuals with mild-moderate COVID-19, 25 individuals with severe COVID-19, and 64 individuals with Chronic COVID-19 symptoms. Immune subset profiling and a 14-plex cytokine panel were run on all patients. Data was analyzed using machine learning methods to predict and distinguish the groups from each other.Using a multi-class deep neural network classifier to better fit our prediction model, we recapitulated a 100% precision, 100% recall and F1 score of 1 on the test set. Moreover, a first score specific for the chronic COVID-19 patients was defined as S1 = (IFN-γ + IL-2)/ CCL4-MIP-1β. Second, a score specific for the severe COVID-19 patients was defined as S2 = (10*IL-10 + IL-6) - (IL-2 + IL-8). Severe cases are characterized by excessive inflammation and dysregulated T cell activation, recruitment, and counteracting activities. While chronic patients are characterized by a profile able to induce the activation of effector T cells with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells.SummaryImmunologic Modeling of Severity and Chronicity of COVID-19

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“…When inflammatory cytokine-producing cells are activated, a virus-induced damage involving predominantly the alveolar epithelium of the lungs occurs [44]. In particular, interferon gamma enhances the immune-mediated damage contributing to the pathogenesis of acute lung injury [45,46]. Studies carried out in patients with ARDS identified different phenotypes depending on the biomarkers found in the serum: ARDS patients with high expression of angiopoietin, plasminogen activator inhibitor 1, interferon gamma and IL-6 had a poorer outcome and a higher mortality compared to ARDS subjects without inflammatory markers [47].…”

Section: The Cytokine Stormmentioning

confidence: 99%

Understanding the dynamics of COVID-19; implications for therapeutic intervention, vaccine development and movement control

Salvamani

Tan

Thang

et al. 2020

British Journal of Biomedical Science

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The COVID-19 disease is caused by the SARS-CoV-2 virus, which is highly infective within the human population. The virus is widely disseminated to almost every continent with over twenty-seven million infections and over ninety-thousand reported deaths attributed to COVID-19 disease. SARS-CoV-2 is a single stranded RNA virus, comprising three main viral proteins; membrane, spike and envelope. The clinical features of COVID-19 disease can be classified according to different degrees of severity, with some patients progressing to acute respiratory distress syndrome, which can be fatal. In addition, many infections are asymptomatic or only cause mild symptoms. As there is no specific treatment for COVID-19 there is considerable endeavour to raise a vaccine against SARS-CoV-2, in addition to engineering neutralizing antibody interventions. In the absence of an effective vaccine, movement controls of varying stringencies have been imposed. Whilst enforced lockdown measures have been effective, they may be less effective against the current strain of SARS-CoV-2, the G614 clade. Conversely, other mutations of the virus, such as the Δ382 variant could reduce the clinical relevance of infection. The front runners in the race to develop an effective vaccine focus on the SARS-Co-V-2 Spike protein. However, vaccines that produce a T-cell response to a wider range of SARS-Co-V-2 viral proteins, may be more effective. Population based studies that determine the level of innate immunity to SARS-CoV-2, from prior exposure to the virus or to other coronaviruses, will have important implications for government imposed movement control and the strategic delivery of vaccination programmes.

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Effects of IFN‐γ on immune cell kinetics during the resolution of acute lung injury

Cited by 29 publications

References 48 publications

The amount of cytokine-release defines different shades of Sars-Cov2 infection

The amount of cytokine-release defines different shades of Sars-Cov2 infection

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

Understanding the dynamics of COVID-19; implications for therapeutic intervention, vaccine development and movement control

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