Role of Senescence and Aging in SARS-CoV-2 Infection and COVID-19 Disease

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic associated with substantial morbidity and mortality worldwide, with particular risk for severe disease and mortality in the elderly population. SARS-CoV-2 infection is driven by a pathological hyperinflammatory response which results in a dysregulated immune response. Current advancements in aging research indicates that aging pathways have fundamental roles in dictating healthspan in addition to lifespan. Our review discusses the aging immune system and highlights that senescence and aging together, play a central role in COVID-19 pathogenesis. In our review, we primarily focus on the immune system response to SARS-CoV-2 infection, the interconnection between severe COVID-19, immunosenescence, aging, vaccination, and the emerging problem of Long-COVID. We hope to highlight the importance of identifying specific senescent endotypes (or “sendotypes”), which can used as determinants of COVID-19 severity and mortality. Indeed, identified sendotypes could be therapeutically exploited for therapeutic intervention. We highlight that senolytics, which eliminate senescent cells, can target aging-associated pathways and therefore are proving attractive as potential therapeutic options to alleviate symptoms, prevent severe infection, and reduce mortality burden in COVID-19 and thus ultimately enhance healthspan.

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Lyapunov function and global asymptotic stability for a new multiscale viral dynamics model incorporating the immune system response: Implemented upon HCV

PLoS ONE ◽

10.1371/journal.pone.0257975 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0257975

Author(s):

Hesham A. Elkaranshawy ◽

Hossam M. Ezzat ◽

Nermeen N. Ibrahim

Keyword(s):

Immune System ◽

Equilibrium Point ◽

Reproduction Number ◽

Initial Conditions ◽

Equilibrium Points ◽

System Response ◽

Viral Dynamics ◽

Wide Range ◽

Immune System Response

In this paper, a new mathematical model is formulated that describes the interaction between uninfected cells, infected cells, viruses, intracellular viral RNA, Cytotoxic T-lymphocytes (CTLs), and antibodies. Hence, the model contains certain biological relations that are thought to be key factors driving this interaction which allow us to obtain precise logical conclusions. Therefore, it improves our perception, that would otherwise not be possible, to comprehend the pathogenesis, to interpret clinical data, to control treatment, and to suggest new relations. This model can be used to study viral dynamics in patients for a wide range of infectious diseases like HIV, HPV, HBV, HCV, and Covid-19. Though, analysis of a new multiscale HCV model incorporating the immune system response is considered in detail, the analysis and results can be applied for all other viruses. The model utilizes a transformed multiscale model in the form of ordinary differential equations (ODE) and incorporates into it the interaction of the immune system. The role of CTLs and the role of antibody responses are investigated. The positivity of the solutions is proven, the basic reproduction number is obtained, and the equilibrium points are specified. The stability at the equilibrium points is analyzed based on the Lyapunov invariance principle. By using appropriate Lyapunov functions, the uninfected equilibrium point is proven to be globally asymptotically stable when the reproduction number is less than one and unstable otherwise. Global stability of the infected equilibrium points is considered, and it has been found that each equilibrium point has a specific domain of stability. Stability regions could be overlapped and a bistable equilibria could be found, which means the coexistence of two stable equilibrium points. Hence, the solution converges to one of them depending on the initial conditions.

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Lung and Gut Microbiota as Potential Hidden Driver of Immunotherapy Efficacy in Lung Cancer

Mediators of Inflammation ◽

10.1155/2019/7652014 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Carmine Carbone ◽

Geny Piro ◽

Vincenzo Di Noia ◽

Ettore D’Argento ◽

Emanuele Vita ◽

...

Keyword(s):

Lung Cancer ◽

Immune System ◽

System Response ◽

Special Focus ◽

Treatment Schedule ◽

Advanced Malignancies ◽

Immune System Response ◽

Epithelial Barriers ◽

And Function

Lung cancer is one of the deadliest and most common malignancies in the world, representing one of the greatest challenges in cancer treatment. Immunotherapy is rapidly changing standard treatment schedule and outcomes for patients with advanced malignancies. However, several ongoing studies are still attempting to elucidate the biomarkers that could predict treatment response as well as the new strategies to improve antitumor immune system response ameliorating immunotherapy efficacy. The complex of bacteria, fungi, and other microorganisms, termed microbiota, that live on the epithelial barriers of the host, are involved in the initiation, progression, and dissemination of cancer. The functional role of microbiota has attracted an accumulating attention recently. Indeed, it has been demonstrated that commensal microorganisms are required for the maturation, education, and function of the immune system regulating the efficacy of immunotherapy in the anticancer response. In this review, we discuss some of the major findings depicting bacteria as crucial gatekeeper for the immune response against tumor and their role as driver of immunotherapy efficacy in lung cancer with a special focus on the distinctive role of gut and lung microbiota in the efficacy of immunotherapy treatment.

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NCMP-05. DECODING THE IMMUNE SYSTEM RESPONSE TO LEPTOMENINGEAL METASTASIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.517 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii124-ii124

Author(s):

Jan Remsik ◽

Xinran Tong ◽

Ugur Sener ◽

Danille Isakov ◽

Yudan Chi ◽

...

Keyword(s):

Immune System ◽

Immune Cells ◽

Leptomeningeal Metastasis ◽

System Response ◽

Idle State ◽

The Central Nervous System ◽

Health And Disease ◽

Immune System Response ◽

Therapeutic Protocols ◽

Brain And Spinal Cord

Abstract For decades, the central nervous system was considered to be an immune privileged organ with limited access to systemic immunity. However, the leptomeninges, the cerebrospinal fluid (CSF)-filled anatomical structure that protects the brain and spinal cord, represent a relatively immune-rich environment. Despite the presence of immune cells, complications in the CSF, such as infectious meningitis and a neurological development of cancer known as leptomeningeal metastasis, are difficult to treat and are frequently fatal. We show that immune cells entering the CSF are held in an ‘idle’ state that limits their cytotoxic arsenal and antigen presentation machinery. To understand this underappreciated neuroanatomic niche, we used unique mouse models and rare patient samples to characterize its cellular composition and critical signaling events in health and disease at a single-cell resolution. Revealing the mediators of CSF immune response will allow us to re-evaluate current therapeutic protocols and employ rational combinations with immunotherapies, therefore turning the patient’s own immune system into an active weapon against pathogens and cancer.

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Cytokine Patterns in Brain Tumour Progression

Mediators of Inflammation ◽

10.1155/2013/979748 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 63

Author(s):

Radu Albulescu ◽

Elena Codrici ◽

Ionela Daniela Popescu ◽

Simona Mihai ◽

Laura Georgiana Necula ◽

...

Keyword(s):

Immune System ◽

Inflammatory Cytokines ◽

Tumour Growth ◽

Tumour Progression ◽

Inflammatory Cells ◽

Serum Levels ◽

Angiogenic Factors ◽

System Response ◽

Gm Csf ◽

Immune System Response

Inflammation represents the immune system response to external or internal aggressors such as injury or infection in certain tissues. The body’s response to cancer has many parallels with inflammation and repair; the inflammatory cells and cytokines present in tumours are more likely to contribute to tumour growth, progression, and immunosuppression, rather than in building an effective antitumour defence. Using new proteomic technology, we have investigated serum profile of pro- (IL-1β, IL-6, IL-8, IL-12, GM-CSF, and TNF-α) and anti-inflammatory cytokines (IL-4, IL-10), along with angiogenic factors (VEGF, bFGF) in order to assess tumoural aggressiveness. Our results indicate significant dysregulation in serum levels of cytokines and angiogenic factors, with over threefold upregulation of IL-6, IL-1β, TNF-α, and IL-10 and up to twofold upregulation of VEGF, FGF-2, IL-8, IL-2, and GM-CSF. These molecules are involved in tumour progression and aggressiveness, and are also involved in a generation of disease associated pain.

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Scaling in the Immune System: PhD Thesis

10.31219/osf.io/b24kw ◽

2019 ◽

Author(s):

soumya banerjee

Keyword(s):

Immune Response ◽

Immune System ◽

Body Size ◽

Human Health ◽

Response Rates ◽

System Response ◽

Metabolic Rates ◽

Viral Dynamics ◽

Immune System Response ◽

Phd Thesis

How different is the immune system in a human from that of a mouse? Do pathogens replicate at the same rate in different species? Answers to these questions have impact on human health since multi-host pathogens that jump from animals to humans affect millions worldwide.It is not known how rates of immune response and viral dynamics vary from species to species and how they depend on species body size. Metabolic scalingtheory predicts that intracellular processes will be slower in larger animals since cellular metabolic rates are slower. We test how rates of pathogenesis and immune system response rates depend on species body size.

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An enhanced agent based model of the immune system response

Cellular Immunology ◽

10.1016/j.cellimm.2006.12.006 ◽

2006 ◽

Vol 244 (2) ◽

pp. 77-79 ◽

Cited By ~ 35

Author(s):

V. Baldazzi ◽

F. Castiglione ◽

M. Bernaschi

Keyword(s):

Immune System ◽

System Response ◽

Agent Based Model ◽

Agent Based ◽

Immune System Response

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A Cognitive Computational Model Inspired by the Immune System Response

BioMed Research International ◽

10.1155/2014/852181 ◽

2014 ◽

Vol 2014 ◽

pp. 1-15

Author(s):

Mohamed Abdo Abd Al-Hady ◽

Amr Ahmed Badr ◽

Mostafa Abd Al-Azim Mostafa

Keyword(s):

Immune System ◽

Computational Model ◽

Cognitive Architecture ◽

Intelligent Agent ◽

System Response ◽

Danger Theory ◽

Proposed Model ◽

Immune System Response ◽

Fuzzy State

The immune system has a cognitive ability to differentiate between healthy and unhealthy cells. The immune system response (ISR) is stimulated by a disorder in the temporary fuzzy state that is oscillating between the healthy and unhealthy states. However, modeling the immune system is an enormous challenge; the paper introduces an extensive summary of how the immune system response functions, as an overview of a complex topic, to present the immune system as a cognitive intelligent agent. The homogeneity and perfection of the natural immune system have been always standing out as the sought-after model we attempted to imitate while building our proposed model of cognitive architecture. The paper divides the ISR into four logical phases: setting a computational architectural diagram for each phase, proceeding from functional perspectives (input, process, and output), and their consequences. The proposed architecture components are defined by matching biological operations with computational functions and hence with the framework of the paper. On the other hand, the architecture focuses on the interoperability of main theoretical immunological perspectives (classic, cognitive, and danger theory), as related to computer science terminologies. The paper presents a descriptive model of immune system, to figure out the nature of response, deemed to be intrinsic for building a hybrid computational model based on a cognitive intelligent agent perspective and inspired by the natural biology. To that end, this paper highlights the ISR phases as applied to a case study on hepatitis C virus, meanwhile illustrating our proposed architecture perspective.

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