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Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics.

ABSTRACT: Emerging infectious diseases always pose a threat to humans along with plant and animal life. SARS-CoV2 is the recently emerged viral infection that originated from Wuhan city of the Republic of China in December 2019. Now, it has become a pandemic. Currently, SARS-CoV2 has infected more than 27.74 million people worldwide, and taken 901,928 human lives. It was named first 'WH 1 Human CoV' and later changed to 2019 novel CoV (2019-nCoV). Scientists have established it as a zoonotic viral disease emerged from Chinese horseshoe bats, which do not develop a severe infection. For example, Rhinolophus Chinese horseshoe bats harboring severe acute respiratory syndrome-related coronavirus (SARSr-CoV) or SARSr-Rh-BatCoV appear healthy and clear the virus within 2-4 months period. The article introduces first the concept of EIDs and some past EIDs, which have affected human life. Next section discusses mysteries regarding SARS-CoV2 origin, its evolution, and human transfer. Third section describes COVID-19 clinical symptoms and factors affecting susceptibility or resistance. The fourth section introduces the SARS-CoV2 entry in the host cell, its replication, and the establishment of productive infection. Section five describes the host's immune response associated with asymptomatic, symptomatic, mild to moderate, and severe COVID-19. The subsequent seventh and eighth sections mention the immune status in COVID-19 convalescent patients and re-emergence of COVID-19 in them. Thereafter, the eighth section describes viral strategies to hijack the host antiviral immune response and generate the "cytokine storm". The ninth section describes about transgenic humane ACE2 (hACE2) receptor expressing mice to study immunity, drugs, and vaccines. The article ends with the development of different immunomodulatory and immunotherapeutics strategies, including vaccines waiting for their approval in humans as prophylaxis or treatment measures.

SUBMITTER: Kumar V

PROVIDER: S-EPMC7843151 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics.

Kumar V V

International immunopharmacology 20200908

Emerging infectious diseases always pose a threat to humans along with plant and animal life. SARS-CoV2 is the recently emerged viral infection that originated from Wuhan city of the Republic of China in December 2019. Now, it has become a pandemic. Currently, SARS-CoV2 has infected more than 27.74 million people worldwide, and taken 901,928 human lives. It was named first 'WH 1 Human CoV' and later changed to 2019 novel CoV (2019-nCoV). Scientists have established it as a zoonotic viral disease ...[more]

PMID: 33182073

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Project description:BackgroundImmune system conditions of the patient is a key factor in COVID-19 infection survival. A growing number of studies have focused on immunological determinants to develop better biomarkers for therapies.AimStudies of the insurgence of immunity is at the core of both SARS-CoV-2 vaccine development and therapies. This paper attempts to describe the insurgence (and the span) of immunity in COVID-19 at the population level by developing an in-silico model. We simulate the immune response to SARS-CoV-2 and analyze the impact of infecting viral load, affinity to the ACE2 receptor, and age in an artificially infected population on the course of the disease.MethodsWe use a stochastic agent-based immune simulation platform to construct a virtual cohort of infected individuals with age-dependent varying degrees of immune competence. We use a parameter set to reproduce known inter-patient variability and general epidemiological statistics.ResultsBy assuming the viremia at day 30 of the infection to be the proxy for lethality, we reproduce in-silico several clinical observations and identify critical factors in the statistical evolution of the infection. In particular, we evidence the importance of the humoral response over the cytotoxic response and find that the antibody titers measured after day 25 from the infection are a prognostic factor for determining the clinical outcome of the infection. Our modeling framework uses COVID-19 infection to demonstrate the actionable effectiveness of modeling the immune response at individual and population levels. The model developed can explain and interpret observed patterns of infection and makes verifiable temporal predictions. Within the limitations imposed by the simulated environment, this work proposes quantitatively that the great variability observed in the patient outcomes in real life can be the mere result of subtle variability in the infecting viral load and immune competence in the population. In this work, we exemplify how computational modeling of immune response provides an important view to discuss hypothesis and design new experiments, in particular paving the way to further investigations about the duration of vaccine-elicited immunity especially in the view of the blundering effect of immunosenescence.

Project description:SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.

Project description:Cancer stem cell (CSC) biology and tumor immunology have shaped our understanding of tumorigenesis. However, we still do not fully understand why tumors can be contained but not eliminated by the immune system and whether rare CSCs are required for tumor propagation. Long latency or recurrence periods have been described for most tumors. Conceptually, this requires a subset of malignant cells which is capable of initiating tumors, but is neither eliminated by immune cells nor able to grow straight into overt tumors. These criteria would be fulfilled by CSCs. Stem cells are pluripotent, immune-privileged, and long-living, but depend on specialized niches. Thus, latent tumors may be maintained by a niche-constrained reservoir of long-living CSCs that are exempt from immunosurveillance while niche-independent and more immunogenic daughter cells are constantly eliminated. The small subpopulation of CSCs is often held responsible for tumor initiation, metastasis, and recurrence. Experimentally, this hypothesis was supported by the observation that only this subset can propagate tumors in non-obese diabetic/scid mice, which lack T and B cells. Yet, the concept was challenged when an unexpectedly large proportion of melanoma cells were found to be capable of seeding complex tumors in mice which further lack NK cells. Moreover, the link between stem cell-like properties and tumorigenicity was not sustained in these highly immunodeficient animals. In humans, however, tumor-propagating cells must also escape from immune-mediated destruction. The ability to persist and to initiate neoplastic growth in the presence of immunosurveillance - which would be lost in a maximally immunodeficient animal model - could hence be a decisive criterion for CSCs. Consequently, integrating scientific insight from stem cell biology and tumor immunology to build a new concept of "CSC immunology" may help to reconcile the outlined contradictions and to improve our understanding of tumorigenesis.

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Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics.

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Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics.

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