CD4+ and CD8+ T Cells in Viral Infections
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Questions and Answers

What specific T cell response is essential for controlling SARS-CoV effectively?

  • Th1 response (correct)
  • Th2 response
  • Th17 response
  • Treg response

    • Which viral protein is most associated with CD4 T cell specificity in SARS-CoV responses?

  • N protein
  • M protein
  • S protein (correct)
  • E protein

    • What cytokine levels are significantly elevated in severe COVID-19 cases compared to moderate cases?

  • Interferon gamma
  • IL-1 and IL-5
  • IL-4 and IL-13
  • IL-2R, IL-6, IL-10, TNF-α (correct)

    • In MERS-CoV infections, what is correlated with disease severity during the convalescent phase?

    <p>Dominance of Th1 type helper T cells</p> Signup and view all the answers

    Which of the following statements about T cell responses to SARS-CoV and MERS-CoV is accurate?

    <p>Virus-specific memory T cells are present in recovered individuals for over a decade post-infection.</p> Signup and view all the answers

    What is the primary function of CD4+ T cells?

    <p>To augment CD8+ cytotoxic T cells and recruit macrophages</p> Signup and view all the answers

    Which cytokine is responsible for the differentiation of T helper cells into Th1 cells?

    <p>IL-12</p> Signup and view all the answers

    What is the main role of CD8+ T cells in the immune response?

    <p>To secrete molecules like perforin and gamma interferon to eradicate viruses</p> Signup and view all the answers

    Which type of T helper cell is primarily involved in mediating allergic responses?

    <p>Th2</p> Signup and view all the answers

    Which antibody is primarily responsible for binding to infected cells and causing antibody-dependent cell cytotoxicity (ADCC)?

    <p>IgG</p> Signup and view all the answers

    What is the key characteristic of IgG antibodies in the immune system?

    <p>They are crucial for secondary immune responses and represent the majority of circulating antibodies.</p> Signup and view all the answers

    What is the primary function of IgM antibodies in the context of viral infections?

    <p>Agglutinate virus particles</p> Signup and view all the answers

    Which cytokines are involved in the differentiation of CD4+ T cells into Th17 cells?

    <p>IL-6 and IL-23</p> Signup and view all the answers

    In the initial immune response to respiratory viral infection, what role do lung-resident respiratory dendritic cells (rDCs) play?

    <p>Present processed antigens to naive T cells</p> Signup and view all the answers

    What is required for effective viral clearance after initial infection?

    <p>CD8+ effector T cell killing and CD4+ T cell enhancement</p> Signup and view all the answers

    What is the primary function of the Fab region of an antibody?

    <p>To bind the antigen</p> Signup and view all the answers

    What characterizes chronic viral infections in terms of T cell responses?

    <p>Persistent antigenic activation leading to T cell exhaustion</p> Signup and view all the answers

    What is the role of T-reg cells in the immune system?

    <p>To promote tolerance and immune suppression</p> Signup and view all the answers

    What occurs to the majority of virus-specific T cells following viral clearance?

    <p>They undergo apoptosis</p> Signup and view all the answers

    Which two types of T cells play crucial roles in the adaptive immune response against viral infections?

    <p>CD8+ and CD4+ T cells</p> Signup and view all the answers

    What is meant by 'opsonization' in the context of viral infections?

    <p>Coating of viral particles for clearance</p> Signup and view all the answers

    What characterizes the T cell profile in patients with moderate to severe COVID-19 during the acute phase?

    <p>Decreased CD4+ and CD8+ T cells</p> Signup and view all the answers

    What does the presence of exhausted phenotype in CD4 and CD8 T cells indicate in critically ill COVID-19 patients?

    <p>High levels of PD-1 and Tim-3 inhibitory markers</p> Signup and view all the answers

    Which cytokines are believed to inhibit T cell circulation in moderate to severe COVID-19?

    <p>IFN-α, IL-6, and TNF-α</p> Signup and view all the answers

    What is the proposed mechanism for the peripheral loss of T cells in patients with severe COVID-19?

    <p>T cell recruitment to sites of infection</p> Signup and view all the answers

    What type of T cell responses are specifically found in convalescent COVID-19 patients?

    <p>Responses specific for Spike, Matrix, and Nucleocapsid proteins</p> Signup and view all the answers

    What indicates a correlation between the development of neutralizing antibodies and T cell activation?

    <p>Higher titers of Nucleocapsid Protein-specific T cells</p> Signup and view all the answers

    Which group had a shift in the balance of antibodies compared to the others?

    <p>Convalescent versus deceased group</p> Signup and view all the answers

    How did the immune response in people who passed away from SARS-CoV-2 differ?

    <p>Increased levels of Nucleocapsid protein-specific antibodies</p> Signup and view all the answers

    What common feature was observed in children affected by past pandemics?

    <p>Significant morbidity and lymphopenia</p> Signup and view all the answers

    Which factor correlated with disease severity during recent pandemics?

    <p>Elevation of systemic innate inflammatory factors</p> Signup and view all the answers

    What is the primary role of IgG antibodies in viral infections?

    <p>Causing antibody-dependent cell cytotoxicity</p> Signup and view all the answers

    IgM antibodies alone are sufficient for clearing virus particles from the body.

    <p>False</p> Signup and view all the answers

    What is opsonization in the context of viral infections?

    <p>Coating of viral particles to enhance clearance.</p> Signup and view all the answers

    Infections characterized by persistent antigenic activation of T cells can lead to T cell ______________.

    <p>exhaustion</p> Signup and view all the answers

    Match the immune cell type with its function:

    <p>CD8+ T cells = Killing of virally infected cells CD4+ T cells = Enhancing B cell responses Lung-resident dendritic cells = Presenting antigen in lymph nodes Memory T cells = Retaining long-term immunity</p> Signup and view all the answers

    What happens to the majority of virus-specific T cells after viral clearance?

    <p>They undergo apoptosis</p> Signup and view all the answers

    What was observed in individuals who passed away from SARS-CoV-2 compared to convalescent individuals?

    <p>Increased Nucleocapsid protein-specific antibodies</p> Signup and view all the answers

    T cell-mediated adaptive immune response is not essential for clearing viral infections.

    <p>False</p> Signup and view all the answers

    Lymphopenia was a common feature observed in children during previous pandemics.

    <p>True</p> Signup and view all the answers

    What initiates the immune response during a respiratory viral infection?

    <p>Direct infection of airway epithelium.</p> Signup and view all the answers

    What type of immune response was associated with the resolution of disease in previous pandemics?

    <p>Virus-specific memory T cells</p> Signup and view all the answers

    A shift in the balance of spike to nucleocapsid antibodies was noted between the convalescent group and the ______ group.

    <p>deceased</p> Signup and view all the answers

    Match the following pandemics with their associated immune response characteristics:

    <p>SARS-CoV-2 = Increased Nucleocapsid protein-specific antibodies in deceased 2009 H1N1 influenza A = Lymphopenia commonly observed 2013 MERS-CoV = Lymphopenia less frequent but severe disease association 2003 SARS = Marked activation of TLR-mediated immune responses</p> Signup and view all the answers

    Which T cell population is decreased in moderate and severe COVID-19 patients?

    <p>CD8+ T cells</p> Signup and view all the answers

    Cytokines such as IFN-α and IL-6 may promote T cell circulation in the blood.

    <p>False</p> Signup and view all the answers

    What is the effect of CD8+ T cell infiltrate in patients with severe COVID-19?

    <p>Increased presence in bronchoalveolar lavage fluid.</p> Signup and view all the answers

    In critically ill patients, CD4 T cells produce inflammatory cytokines such as ______.

    <p>GM-CSF</p> Signup and view all the answers

    Match the T cell phenotypes with their characteristics:

    <p>Exhausted phenotype = Upregulated expression of inhibitory markers Activated CD4 T cells = Production of inflammatory cytokines Reduced T regulatory cells = Loss of immune modulation Increased CD8 T cell infiltrate = Presence in bronchoalveolar lavage fluid</p> Signup and view all the answers

    What correlates with COVID-19-associated disease severity and mortality?

    <p>Decrease in CD8+ T cells</p> Signup and view all the answers

    Direct viral infection of T cells has been reported in COVID-19 cases.

    <p>False</p> Signup and view all the answers

    What remains unclear regarding T cell loss in moderate to severe COVID-19?

    <p>The mechanisms contributing to peripheral T cell loss.</p> Signup and view all the answers

    Which cytokine does NOT play a role in inhibiting T cell circulation in COVID-19?

    <p>TNF-β</p> Signup and view all the answers

    The primary T cell responses specific for SARS-CoV proteins are found in ______ patients.

    <p>convalescent</p> Signup and view all the answers

    What is the primary cytokine secreted by activated CD4+ T cells in response to SARS-CoV-2?

    <p>Interferon gamma</p> Signup and view all the answers

    SARS-CoV-2 specific CD8+ T cells predominantly exhibit a central memory phenotype.

    <p>False</p> Signup and view all the answers

    What type of T cell response is associated with less severe COVID-19 disease?

    <p>CD4+ T cell response</p> Signup and view all the answers

    Healthy individuals who have previously been exposed to __________ responded better to SARS-CoV-2 infection.

    <p>common cold coronaviruses</p> Signup and view all the answers

    Which of the following T cell types is mainly responsible for cytotoxic activity against SARS-CoV-2?

    <p>CD8+ T cells</p> Signup and view all the answers

    What T cell subset appears to be more activated in response to infections?

    <p>CD8 T cells</p> Signup and view all the answers

    Match the T cell type with its characteristic:

    <p>CD4+ T cells = Secreting interferon gamma CD8+ T cells = Displaying effector memory phenotype CCR7+CD45- = Central memory T cells CCR7-CD45- = Effector memory T cells</p> Signup and view all the answers

    SARS-CoV-2 specific T cells are entirely absent in non-exposed individuals.

    <p>False</p> Signup and view all the answers

    CD4 T cells are the primary subset involved in the exhaustion observed in critically ill COVID-19 patients.

    <p>False</p> Signup and view all the answers

    The majority of SARS-CoV-2 CD4+ T cells exhibit a __________ phenotype.

    <p>CCR7+CD45-</p> Signup and view all the answers

    What is the time frame in days when neutralizing antibodies to the Spike protein typically peak after infection?

    <p>20-30 days</p> Signup and view all the answers

    Individuals who recovered from SARS-CoV have detectable Spike-specific IgG and neutralizing antibodies after _____ months.

    <p>12</p> Signup and view all the answers

    In patients with mild COVID-19 disease, what correlates with viral clearance?

    <p>Early induction of CD4+ T cells secreting interferon gamma</p> Signup and view all the answers

    What is a characteristic feature of severe COVID-19 cases concerning T cell function?

    <p>Poor polyfunctionality and proliferative capacity</p> Signup and view all the answers

    Match the following immune responses with their characteristics:

    <p>IgG antibodies = Appear early and correlate with neutralizing antibody titers Memory T cell responses = Detected in a majority of SARS patients even six years post infection Neutralizing antibodies = Peak at 20-30 days after infection Inhibitory markers = Common in severely ill COVID-19 patients</p> Signup and view all the answers

    Which of the following markers indicates an exhausted T cell state in severely ill patients?

    <p>PD-1</p> Signup and view all the answers

    Antibody responses to SARS-CoV are typically lower in patients with severe outcomes compared to those with milder illnesses.

    <p>True</p> Signup and view all the answers

    What percentage of patients had memory T cell responses detected six years after SARS infection?

    <p>60%</p> Signup and view all the answers

    In recovering patients, there is an increase in follicular helper T cells and effector molecules such as Gzm A, Gzm B, and ________.

    <p>perforin</p> Signup and view all the answers

    Which T cell subset is associated with higher expression of co-stimulatory and inhibitory molecules?

    <p>Effector T cells</p> Signup and view all the answers

    Study Notes

    CD4+ and CD8+ T Cell Roles in Viral Infection

    • CD4+ T cells produce cytokines that augment CD8+ cytotoxic T cells and macrophage recruitment.
    • CD8+ cytotoxic T cells (CTLs) secrete perforin, granzymes, and gamma interferon to eradicate viruses from the host.
    • CD4+ and CD8+ T cells collaborate with other cells to resolve acute viral infections and provide protection against reinfection.
    • Delineating the frequency, specificity, functionality, and durability of T cells during COVID-19 is vital for understanding their use as biomarkers and targets for immunotherapies and vaccines.

    T Helper Cell Differentiation

    • CD4+ T helper cells differentiate into four subtypes: Th1, Th2, Th17, and T-reg.
    • Th1: Cellular immunity, inflammation clearance of intracellular pathogens (stimulated by IL-12).
    • Th2: Humoral immunity, allergic responses (stimulated by IL-4).
    • Th17: Tissue inflammation, autoimmunity, clearance of extracellular pathogens (stimulated by IL-6 and IL-23).
    • T-reg: Tolerance, immune suppression.

    Antibody Function and Types

    • Antibodies bind antigens, neutralize or block antigen activities.
    • Antibodies trigger immune responses by engaging Fc receptors on immune cells.
    • Complement binding to the antibody-antigen complex results in pathogen lysis.
    • IgM is the first antibody produced in a primary immune response, comprising 10% of the total antibody pool.
    • IgG is the major human serum immunoglobulin (60-70% of total circulating antibodies), playing a key role in the secondary immune response.

    Antibodies in Viral Infection

    • IgG, IgM, and IgA antibodies can neutralize extracellular viruses before infection.
    • Only IgG antibodies can bind to infected cells and cause antibody-dependent cell cytotoxicity (ADCC).
    • ADCC utilizes antibody-mediated complement lysis to kill infected cells.
    • IgG, IgM, and IgA antibodies block virus/cell interactions.
    • IgM antibodies can agglutinate viral particles.
    • IgM and IgG can opsonize viral particles for clearance.

    T Cell Responses to Respiratory Virus Infection

    • The immune response begins with direct airway epithelium infection.
    • Lung-resident respiratory dendritic cells (rDCs) acquire the virus or antigens from infected epithelial cells, become activated, process antigen, and migrate to the draining lymph nodes (DLN).
    • In the DLNs, rDCs present the processed antigen as an MHC/peptide complex to naive circulating T cells.
    • Engagement of the T cell receptor (TCR) with the peptide–MHC complex and additional co-stimulatory signals activates T cell proliferation and migration to the site of infection (the lung) to perform their effector function.

    Immune Dysregulation During Chronic Viral Infection

    • T cell–mediated adaptive immunity is crucial for clearing and maintaining long-term suppression of viral infections.
    • Effective viral clearance requires both CD8+ effector T cell–mediated killing of virally infected cells and CD4+ T cell–dependent enhancement of CD8+ and B cell responses.
    • Following viral clearance, most virus-specific T cells undergo apoptosis, but retaining a virus-specific memory T cell population is necessary for long-term antiviral immunity.
    • Chronic viral infections evade or suppress adaptive immunity.
    • Persistent antigenic activation of T cells drives a nonresponsive cell state or T cell “exhaustion.”

    T Cell Immune Responses to SARS-CoV-2

    • Marked leukopenia (dramatic loss of CD4+ and CD8+ T cells).
    • Severe infection delays the development of the adaptive immune response and prolongs virus clearance.
    • T cell epitopes are found in the S, N, and M viral proteins. Most CD4+ T cells are specific for the S protein.
    • Th1 response is key for successful control of SARS-CoV-2.
    • The magnitude and frequency of CD8+ memory T cells exceed those of CD4+ memory T cells.
    • Virus-specific memory CD4+ and CD8+ T cells are found in individuals who recovered from the infection at least 10 years after acute infection.

    T Cell Immune Response to MERS-CoV

    • High frequencies of MERS-CoV-reactive CD8+ T cells are observed in patients with severe/moderate illness before detection of Abs and CD4+ T cell responses.
    • A strong specific T-cell response against the MERS-CoV S protein is observed on day 24 after disease onset.
    • All deceased patients displayed rapid drops in their lymphocyte counts.
    • IL-12 and interferon gamma levels are lower in a fatal case than in a patient who survived the infection.
    • An early rise of CD8+ T cells correlates with disease severity, and at the convalescent phase, dominant Th1 type helper T cells are observed.

    Plasma Cytokine Levels in Patients with COVID-19: The Cytokine Storm

    • Levels of interleukin 2R (IL-2R), IL-6, IL-10, and tumor necrosis factor α (TNF-α) are markedly higher in severe cases than in moderate cases.

    Lymphopenia in COVID-19

    • Marked lymphopenia (drop in lymphocytes) is observed in T cells in patients with the acute phase of infection.

    Changes in the Phenotype of T Cells in the Peripheral Blood

    • Reduced CD4+ and CD8+ T cells in moderate and severe COVID-19 in the acute phase.
    • Decreases in CD8+ T cells in patients admitted to the ICU correlate to COVID-associated disease severity and mortality.
    • Increases in activated CD4+ and CD8+ T cells displaying an exhausted phenotype (upregulated expression of inhibitory markers like PD-1 and Tim-3) in persistent COVID-19.
    • Production of inflammatory cytokines such as GM-CSF by CD4+ T cells in critically ill patients.
    • Reduced frequencies of T regulatory cells in severe COVID-19.

    Mechanisms Contributing to Reduced T Cells in the Blood

    • The cause of peripheral T cell loss in moderate to severe COVID-19 remains elusive.
    • A similar phenomenon is observed in other viral infections.
    • Cytokines like IFN-α, IL-6, and TNF-α may inhibit T cell circulation in blood by promoting retention in lymphoid organs and attachment to endothelium.
    • T-cell recruitment to sites of infection can reduce their presence in the peripheral blood (increased CD8+ T cell infiltrate in bronchoalveolar lavage fluid).
    • Direct viral infection has not been reported.

    CD4+ and CD8+ T Cell Responses in Convalescent COVID-19 Patients

    • T cell responses specific for Spike, Matrix, and Nucleocapsid proteins are found in convalescent COVID-19 patients.
    • A correlation exists between the neutralizing antibody titers and the number of Nucleocapsid Protein-specific T cells, suggesting a link between neutralizing antibody development and antiviral T cell activation.

    Serological Signatures Track with SARS-CoV-2 Survival

    • Limited early differences exist in titer and neutralization.
    • A shift occurs in the balance of spike to nucleocapsid antibodies in convalescent versus deceased groups.
    • Spike-specific phagocytic and complement-fixing activity is increased in convalescent individuals.
    • Individuals who passed away from SARS-CoV-2 had increased Nucleocapsid protein-specific antibodies.

    Immunological Similarities between COVID-19 and Recent Pandemics

    • 2003 SARS-CoV pandemic:
      • SARS-CoV viral particles significantly activated TLR-mediated innate immune responses.
      • Lymphopenia occurred in most patients and was associated with severe disease.
      • SARS also significantly affected children, in whom lymphopenia was a common feature.
      • Development of virus-specific memory T cells was associated with disease resolution and protection from subsequent infection.
    • 2009 H1N1 influenza A pandemic:
      • Lymphopenia occurred in the majority of patients.
      • Occurred frequently and caused lymphopenia and significant morbidity in children.
      • Marked elevation of systemic innate inflammatory factors, including MCP-1 and IL-6, with elevated IL-6 correlating with disease severity.
    • 2013 MERS-CoV pandemic:
      • Lymphopenia occurred less frequently but was associated with disease severity, and recovery was associated with improved outcomes.
      • Neutralizing antibodies to MERS and MERS-CoV–specific CD4+ T cells correlated with disease severity.

    Involvement in Viral Infection

    • Only IgG antibodies directly attack infected cells, using antibody-dependent cell cytotoxicity (ADCC) and complement lysis
    • All three types of antibodies (IgG, IgM, and IgA) prevent virus/cell interactions.
    • IgM antibodies agglutinate (clump) viral particles
    • IgM and IgG antibodies opsonize viral particles, tagging them for immune system clearance.

    Immune Responses to Respiratory Virus Infection

    • Lung-resident respiratory dendritic cells (rDCs) are the first to encounter the virus or antigens from infected epithelial cells
    • rDCs become activated, process antigens, and migrate to draining lymph nodes (DLNs)
    • In DLNs, rDCs present processed antigens via MHC/peptide complexes to naive circulating T cells
    • Engagement of the T cell receptor (TCR) with the MHC/peptide complex and co-stimulatory signals activate T cell proliferation and migration to the lungs, where they perform their effector functions.

    Immune Dysregulation During Chronic Viral Infection

    • CD8+ effector T cells kill virally infected cells, and CD4+ T cells enhance CD8+ and B cell responses, crucial for viral clearance
    • Most virus-specific T cells undergo apoptosis following viral clearance, but memory T cells are vital for long-term antiviral immunity
    • Chronic viral infections evade or suppress adaptive immunity
    • Persistent antigenic activation of T cells leads to T cell exhaustion, a dysfunctional state

    Changes in the Phenotype of T Cells in the Peripheral Blood

    • Marked lymphopenia in patients with acute phase of infection
    • Reduced CD4+ and CD8+ T cells in Moderate and severe COVID-19 in acute phase
    • Decrease in CD8+ T cells in patients admitted to Intensive Care Unit (ICU) correlates with COVID-associated disease severity and mortality
    • Increased activated CD4 and CD8 T cells with an exhausted phenotype, characterized by upregulated expression of inhibitory markers like PD-1 and Tim-3 in persistent COVID
    • Production of inflammatory cytokines such as GM-CSF (Granulocyte-Macrophage Colony-Stimulating factor) by CD4 T cells in critically ill patients.
    • Reduced frequencies of T regulatory cells in severe COVID-19

    Mechanisms Contributing to Reduced T Cells in the Blood

    • The cause of peripheral T cell loss in moderate to severe COVID-19 remains unclear.
    • This phenomenon is observed in other viral infections as well.
    • Cytokines like IFN-α, IL-6, and TNF-α may inhibit T cell circulation by promoting retention in lymphoid organs and attachment to endothelium
    • T cell recruitment to infection sites may reduce their presence in the peripheral blood, as seen by increased CD8 T cell infiltration in bronchoalveolar lavage fluid
    • Direct viral infection has not been reported.

    CD4 and CD8 T Cell Responses

    • T cell responses specific to Spike, Matrix, and Nucleocapsid proteins are found in convalescent COVID patients.
    • T cell reactivity to SARS-CoV-2 is detectable in individuals with no prior exposure.

    Anti-viral T Cell Responses

    • SARS-CoV-2 specific T cells are observed in most individuals
    • CD4 and CD8 T cell responses target different antigens, mostly Spike and Nucleocapsid proteins
    • The majority of SARS-CoV-2 CD4+ T cells exhibit a CCR7+CD45- phenotype (central memory - 50-60%) and some exhibit a CCR7-CD45- phenotype (effector memory - 25-40%)
    • SARS-CoV-2 CD8+ T cells predominantly express the effector memory phenotype
    • SARS-CoV-2 specific CD4 and CD8 T cells display a Th1 profile with increased cytotoxic activity and elevated expression of immune activation markers.

    Pro-inflammatory Cytokine Secretion Profile

    • Activated CD4+ T cells produce high amounts of cytokines, whether activated by Spike or non-Spike proteins

    SARS-CoV-2-Specific T Cells and Associations with Disease Severity

    • Detection of an early SARS-Cov2 CD4+ T cell response is associated with less severe disease than antibody response or CD8+ T cell response.
    • Early induction of CD4+ T cells secreting interferon gamma occurs much earlier in patients with mild disease and correlates with viral clearance
    • Preliminary evidence suggests very rapid induction of CD8+ T cells might lead to asymptomatic disease
    • Severe COVID-19 is associated with poor polyfunctionality and proliferative capacity and enhanced immune activation.

    Cytokine Profile of CD4 and CD8-Specific T Cells to SARS-CoV2 Proteins

    • SARS-CoV-2 reactive CD4+ T cells have been detected in unexposed individuals
    • There's a spectrum of pre-existing memory CD4+ T cells that are cross-reactive with SARS-CoV-2 and common cold coronaviruses (HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1)
    • Healthy individuals previously exposed to common cold coronaviruses respond better to SARS-CoV-2 infection.

    Phenotype and Function of T Cell Subsets

    • Increase in activated T cells, characterized by expression of HLA-DR, CD38, CD69, CD25, CD44, and Ki-67
    • CD8 T cells seem to be more activated than CD4 T cells
    • Higher expression of various co-stimulatory and inhibitory molecules like OX-40, CD137, CTLA-4, NKG2a, and TIGIT
    • Levels of most markers tend to increase in severe versus non-severe cases
    • Impaired functionality in CD4 and CD8 T cells in critically ill patients
    • T cells in severe COVID-19 appear to be more activated and exhausted, based on continuous expression of inhibitory markers like PD-1 and Tim-3
    • Increase in Follicular Helper T cells (Tfh) and effector molecules like Gzm A, Gzm B, and perforin, but a decrease in levels of inhibitory molecules in recovering patients.

    B cell Immunity to SARS-CoV

    • IgG antibodies appear early on (day 4-45) after symptom onset
    • IgG antibody and neutralizing antibody (Nab) titers are highly correlated, peaking at month 4 after disease onset, with marked decrease at 2 years post-infection
    • Nabs to Spike protein peak at 20–30 days after infection and are sustained for over 150 days. NAb titers decrease markedly after month 16.
    • IgG level of mild patients is significantly higher than that of severe patients
    • SARS-CoV-infected patients with fatal outcomes display deficient antibody production against the S protein compared to non-severe patients.

    Antibody Responses to SARS-CoV

    • One year after infection, Spike-specific IgG and neutralizing antibodies are detected in recovered individuals compared to high-risk healthy controls.
    • Healthy individuals do not have any Spike-specific antibodies

    Specific Memory T and B Cell Responses to SARS-CoV

    • Memory T cell responses were detected in 60% of SARS patients six years after infection
    • T cell response is much stronger than B cell or antibody response.
    • No SARS-specific memory B cell responses were detected.

    Correlation Between Neutralizing Antibody Titers and Anti-viral T Cell Activity

    • There's a correlation between neutralizing antibody titers and the number of Nucleocapsid Protein-specific T cells, suggesting that the development of neutralizing antibodies may be correlated with the activation of anti-viral T cells

    Serological Signatures Track with SARS-CoV-2 Survival

    • Limited early differences were seen in titers and neutralization
    • A shift in the balance of Spike to Nucleocapsid antibodies is observed in convalescent versus deceased groups
    • Spike-specific phagocytic and complement-fixing activity was increased in convalescent individuals
    • Individuals that passed away from SARS-CoV-2 had increased Nucleocapsid protein-specific antibodies.

    2003 CoV Pandemic

    • SARS-CoV viral particles markedly activated TLR-mediated innate immune responses
    • Lymphopenia occurred in the majority of patients and was associated with severe disease
    • Lymphopenia was a common feature in children, significantly impacting them
    • Development of virus-specific memory T cells was associated with disease resolution and protection from subsequent infection.

    Immunological Similarities Between COVID-19 and Recent Pandemics?

    • Lymphopenia occurred in the majority of patients during the 2009 H1N1 influenza A pandemic and was also a frequent occurrence with significant morbidity in children.
    • Marked elevation of systemic innate inflammatory factors like MCP-1 and IL-6, and elevated IL-6 correlated with disease severity.
    • In the 2013 MERS-CoV pandemic, lymphopenia occurred less frequently, but was associated with disease severity, and recovery was associated with improved outcomes.
    • Neutralizing antibodies to MERS and MERS-CoV–specific CD4+ T cells correlated with disease severity.

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