COVID-19 Immunopathogenesis – PPT & pdf file

COVID-19 was the worst disaster which started spreading in 2019. The COVID-19 virus is a very invasive pathogen, and it was hard to break down its spreading in the world. In this presentation, we talk about the process of COVID-19 development involving an immune response or components thereof. If we have enough information about the Immunopathogenesis of COVID-19, it would be easier to control the morbidity rate of this disease. We try to clarify some common questions about COVID-19 Immunopathogenesis, such as:

What are the key immunological features associated with severe COVID-19 cases?
How does the SARS-CoV-2 virus impact lymphocyte populations?
What role do cytokine storms play in COVID-19 pathogenesis?
The document “COVID-19 Immunopathogenesis” discusses the intricate mechanisms through which the SARS-CoV-2 virus manipulates and dysregulates the human immune system, leading to severe clinical manifestations observed in COVID-19 patients. At the onset, the virus’s impact on various immune cell populations is profound, with notable reductions in T CD4+, T CD8+, NK, and B cells, a phenomenon known as lymphopenia. This depletion of immune cells is a hallmark of severe COVID-19 cases, indicating a potential biomarker for predicting disease severity.

In addition to depleting immune cells, the virus also alters their function. CD8+ T cells, critical for viral clearance, show increased activation but also signs of exhaustion, characterized by increased expression of inhibitory markers such as PD1 and TIM3. This exhaustion limits the effectiveness of the immune response against the virus.

Cytokine storms, where there is an uncontrolled release of inflammatory cytokines, are another critical aspect of COVID-19’s immunopathogenesis. The document highlights the extreme increase in pro-inflammatory cytokines in severe cases, contributing to multi-organ dysfunction and the often-lethal complications seen in severely ill patients. Antibody responses are also examined, with elevated levels of IgG being closely associated with disease severity. However, the balance between protective immunity and harmful immune responses remains a subject of intense study.

The document references several key studies, from the Lancet and JAMA to support its findings. For instance, the work by Chen et al. (2020) provides a descriptive study of the clinical characteristics of 99 cases of COVID-19 in Wuhan, China, while Wang et al. (2020) details the clinical characteristics of 138 hospitalized patients. Additionally, Li et al. (2004) discuss significant changes in peripheral T lymphocyte subsets during severe acute respiratory syndrome (SARS), providing a comparative perspective.

Reference:
https://sciencecodons.com/2926-covid-19-immunopathogenesis/

1. COVID-19 Immunopathogenesis 1

2. Table of contents The immunopathology of Covid-19 Potential mechanism of SARS Cov-2 induced immunopathology. Clinical implications of SARS Cov-2 induced immunopathology. 2

3. Introduction Corona virus disease 2019 (COVID-19) is a clinical syndromes caused by a mutational RNA virus named as severe acute respiratory syndrome corona virus (SARS Cov-2). After initially occurring in China in December 2019, it spread all over the world and accepted as a pandemic by the World Health Organization (WHO) in March 2020. SARS Cov-2 is a beta-corona virus, similar to two other corona virus is SARS Covid and MERS covid. 3

4. The Immunopathology of COVID 19 It has been shown that SARS cov-2 disrupts normal immune responses leading to an impaired immune system and uncontrolled inflammatory responses in severe and critical patients with COVID-19. These patients exhibit lymphopenia, lymphocyte activation and dysfunction, granulocyte and monocyte abnormalities, high cytokine levels and an increase in lgG and total antibodies. 4

5. Lymphopenia Lymphopenia is a key feature of patients with Covid 19, especially in severe cases. Patients with severe COVID 19 are more likely to exhibit lymphopenia on a dismission, indicating a significant predictor for severe patients. Patients also show a marked reduction in T CD4+, T CD8+ Nk , B cell. Lymphocyte percentage were found to be lower than 20% in severe cases. These data indicate that lymphopenia can be used an indicator of disease severity and prognosis of patients with COVID 19.   5

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7. Lymphocyte Activation It is one study with 123 convalescent samples, the CD T cell response occurred more frequently than the CD4+ T cell response. Furthermore, virus-specific T cells from severe cases presented with a central memory phenotype and high levels of IFN-y, TNF- α and il-2 compared with that of the mild group. Reported that CD69, CD38, OX40, 4-1BB and CD44 are highly expressed on CD4 and CD T cells of patients with COVID 19 compared with healthy contents.   7

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9. Lymphocyte Dysfunction In addition, T cells in patients with covid 19 show exhaustion phenotypes. PD1 and TIM3 levels in CD8+ T cells are increased in overtly symptomatic stages compared with the prodromal stage and peak levels are detected in severe conditions. More over, NKG2A expression on cytotoxic lymphocytes, including NK and CD8+ T cells is elevated. 9

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11. Increased Production of Cytokines Increased cytokine production is another key characteristic of severe COVID 19. Most severe COVID 19 cases exhibit an extreme increase inflammatory cytokines In particular, il1 β , il6 and il10. 11

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13. Increase Antibodies Interestingly found that an increase IgG response is closely associated with disease severity, indicating a simple marker to discriminate between severe and non severe. 13

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15. Potential Mechanisms of SARS-COV-2-Induced Immunopathology Depletion and Exhaustion of Lymphocytes: Thera are several potential mechanisms responsible for lymphocyte depletion and dysfunction: SARS-COVID 2 can directly infect T cells and macrophages. A concomitant increase in inflammatory cytokine levels promotes the depletion and exhaustion. SARS-COVID 2 directly damages lymphatic organs including the spleen and lymphnodes . Increased lactic acid levels inhibit the proliferation and dysfunction lymphocytes in blood. 15

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17. Increased Neutrophils Regarding neutrophil upregulation in patients with COVID 19, we can theorize a close association with lymphopenia. It is known that infection with microbe can directly induce neutrophil recruitment to tissue site. 17

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19. Cytokine Storm In patients with severe COVID 19, there is an abundance of cytokine production, inducing a cytokine storm in addition to a series of adverse reactions in the human body. CD4 T cells can be rapidly activated in to Th1 cells that secret GM-CSF further inducing CD monocytes with high il-6 levels. An increase in the CD il-1 β monocyte subpopulation promotes increased il-1 β production. Th 17 cells produce il-17 to further recruit monocytes, macrophages and neutrophils and stimulate other cytokine cascades, such as il-1 β and il-6 among other.   19

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21. Antibody Dependent Enhancement (ADE) The antibody dependent enhancement (ADE) of virus infection is a phenomenon in which pre-existing sub-neutralizing antibodies enhance virus entry and replication. 21

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23. Clinical Implications of SARS-COV-2-Induced Immunopathology The Effect of Lymphopenia On Microbial Infection: Lymphopenia is a common feature in patients with COVID-19. Patients with COVID-19 are more prone to infections with microbe, which leads to disease progression and increased severity. (1,3)-β-D-glucan in patients with severe COVID-19 and low lymphocyte are significantly higher than in patients with high lymphocyte levels. 23

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25. The Effect Of Elevated Cytokine Production Of Clinical Manifestations Cytokine storm can initiate inflammatory-induced multiple organ. Dysfunction, including lung injury that can lead to ARDS, respiratory failure, liver injury with alanine aminotransferase (Alt), aspartat aminotransferase (AST), and y-glutamine transferase (y-GT) upregulation, kidney injury with increased area and creatine levels, and heart injury with increased creatine kinase (ck) and lactate dehydrogenase (LDH) levels. 25

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27. References 1. Zhu, N. et al. A Novel Coronavirus from patients with Pneumonia in China, 2019. N. Engl. J. Med. 382, 727–733 (2020). 2. Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020). 3. Chen, N. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395, 507–513 (2020). 4. Wang, D. et al. Clinical characteristics of 138 hospitalized patients with 2019 Novel Coronavirus-infected Pneumonia in Wuhan, China. JAMA. 323, 1061–1069 (2020). 5. Li, T. et al. Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome. J. Infect. Dis. 189, 648–651 (2004). 6. Cui, W. et al. Expression of lymphocytes and lymphocyte subsets in patients with severe acute respiratory syndrome. Clin. Infect. Dis. 37, 857–859 (2003). 7. Cimini , E. et al. Different features of Vdelta2 T and NK cells in fatal and non-fatal human Ebola infections. PLoS Negl . Trop. Dis. 11, e0005645 (2017). 8. Reynard, S. et al. Immune parameters and outcomes during Ebola virus disease. JCI Insight. 4, e125106 (2019). 27

28. Thanks for your attention! 28