An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019

Bordoni, Veronica; Sacchi, Alessandra; Cimini, Eleonora; Notari, Stefania; Grassi, Germana; Tartaglia, Eleonora; Casetti, Rita; Giancola, Maria Letizia; Bevilacqua, Nazario; Maeurer, Markus; Zumla, Alimuddin; Locatelli, Franco; Benedetti, Fabrizio; Palmieri, Fabrizio; Marchioni, Luisa; Capobianchi, Maria Rosaria; D’Offizi, Gianpiero; Petrosillo, Nicola; Antinori, Andrea; Nicastri, Emanuele; Ippolito, Giuseppe; Agrati, Chiara

doi:10.1093/cid/ciaa577

Cited by 99 publications

(105 citation statements)

References 13 publications

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Section: Pathogen Eliminationmentioning

confidence: 99%

“…Relative to HC's, significantly elevated frequencies of MDSC's ( 235 ) and granulocytic-MDSC's (G-MDSCs) ( 236 ) have been detected in peripheral blood samples obtained from mild and severe COVID-19 patients. Suggestive of driving reduced anti-viral immune responses, significant negative associations were reported between MDSC frequency and the percentage of perforin + CD3 + T cells and perforin + NK cells ( 235 ), whilst in ex vivo cultures, depletion of G-MDSC's from PBMC samples of severe COVID-19 patients restored the proliferative capacity and cytokine production of T cells ( 236 ). In terms of disease severity, MDSC frequency has been reported to be significantly higher in patients with severe COVID-19 when compared to subjects with mild disease ( 236 ), whilst single cell transcriptomics has revealed the presence of immature CD14 + MPO + Ki67 + HLA-DR lo suppressive monocytes and immature ARG1 + CD101 + S100A8/A9 + neutrophils only in patients with severe disease ( 237 ).…”

Section: Pathogen Eliminationmentioning

confidence: 99%

“…Furthermore, there is evidence to suggest that MDSC's persist in severe patients, with one study reporting G-MDSC's comprised >30% of total PBMC's in samples acquired from 3 severe COVID-19 patients at day 18 post-hospital admission ( 236 ). Thus, it has been hypothesized that a SARS-CoV-2-induced expansion of MDSC's may promote immune paralysis and that current therapeutic approaches targeting the cytokine storm may have the additional benefit of augmenting anti-viral immune responses by reducing MDSC proliferation and activation ( 235 ).…”

Section: Pathogen Eliminationmentioning

confidence: 99%

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Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

Hazeldine

Lord

2020

Front. Immunol.

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Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile, could immunesenescence be a generic contributory factor in the development of severe COVID-19? Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.

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Section: Pathogen Eliminationmentioning

confidence: 99%

Section: Pathogen Eliminationmentioning

confidence: 99%

Section: Pathogen Eliminationmentioning

confidence: 99%

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Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

Hazeldine

Lord

2020

Front. Immunol.

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“…There are commonalities between immune responses involved in the acquisition of skin sensitization and those that are induced by pathogenic microorganisms. [8][9][10] This begs the question of whether immune responses to microbial antigens and those induced by contact allergens could display co-operative effects, and if so, whether this could be exploited as a mechanism for enhancing the immunogenicity of viral vaccines. This could be through different pathways that augment each other, or directly shared common pathways.…”

Section: The Immunological Responses To Contact Allergens and Virusmentioning

confidence: 99%

“…Directly shared pathways include natural killer (NK) cell activity and perforin expression, which appear to be crucial for both the response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in the innate and memory response in contact sensitization. [9][10][11][12] Another example of a "common" pathway between responses to a respiratory virus and contact allergens is NLRP3 activation. 13,14 Danger signals can take a variety of forms, but it is convenient to…”

Section: The Immunological Responses To Contact Allergens and Virusmentioning

confidence: 99%

Harnessing co‐operative immune augmentation by contact allergens to enhance the efficacy of viral vaccines

et al. 2020

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Although the development of successful vaccines against coronaviruses may be achieved, for some individuals the immune response that they stimulate may prove to be insufficient for effective host defence. The principle that a relatively strong contact allergen will have an enhancing effect on sensitization compared with a less potent contact allergen if they are co-administered, may not, at first, appear relevant to this issue. However, this augmentation effect is thought to be due to the sharing of common or complementary pathways. Here, we briefly consider aspects of the shared and complementary pathways between skin sensitization induced by exposure to a contact allergen and the immune response to viruses, with particular reference to COVID-19. The relationship leads us to explore whether this principle, which we name here as "co-operative immune augmentation" may be extended to include viral vaccination. We consider evidence that even relatively weak contact allergens, used in vaccines for other purposes, can show enhanced sensitization, which is in keeping with a cooperative augmentation principle. Finally, we consider how the potent contact allergen diphenylcyclopropenone could be employed safely as an enhancer of vaccine responses.

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Computational framework to understand the clinical stages of COVID‐19 and visualization of time course for various treatment strategies

Sharma

Sarkar

Mitra

et al. 2023

Biotech & Bioengineering

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Coronavirus disease 2019 is known to be regulated by multiple factors such as delayed immune response, impaired T cell activation, and elevated levels of proinflammatory cytokines. Clinical management of the disease remains challenging due to interplay of various factors as drug candidates may elicit different responses depending on the staging of the disease. In this context, we propose a computational framework which provides insights into the interaction between viral infection and immune response in lung epithelial cells, with an aim of predicting optimal treatment strategies based on infection severity. First, we formulate the model for visualizing the nonlinear dynamics during the disease progression considering the role of T cells, macrophages and proinflammatory cytokines. Here, we show that the model is capable of emulating the dynamic and static data trends of viral load, T cell, macrophage levels, interleukin (IL)-6 and TNF-α levels. Second, we demonstrate the ability of the framework to capture the dynamics corresponding to mild, moderate, severe, and critical condition. Our result shows that, at late phase (>15 days), severity of disease is directly proportional to pro-inflammatory cytokine IL6 and tumor necrosis factor (TNF)-α levels and inversely proportional to the number of T cells. Finally, the simulation framework was used to assess the effect of drug administration time as well as efficacy of single or multiple drugs on patients. The major contribution of the proposed framework is to utilize the infection progression model for clinical management and administration of drugs inhibiting virus replication and cytokine levels as well as immunosuppressant drugs at various stages of the disease.

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An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019

Cited by 99 publications

References 13 publications

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

Harnessing co‐operative immune augmentation by contact allergens to enhance the efficacy of viral vaccines

Computational framework to understand the clinical stages of COVID‐19 and visualization of time course for various treatment strategies

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