The Role of Immunity in the Pathogenesis of SARS-CoV-2 Infection and in the Protection Generated by COVID-19 Vaccines in Different Age Groups
Abstract
:1. Introduction
2. Review of the Literature and Discussion
2.1. Development and Maturation of the Normal Immune System
2.1.1. The First Stage during Infancy
Innate Immunity
Adaptive Immunity
2.1.2. The Second Stage: From Childhood to Adolescence–Adulthood
3. Immune Response to the Different Types of Vaccines in Children
3.1. Immune Response to COVID-19 Vaccines
3.2. Safety of Anti-COVID-19 Vaccines from Infancy to Adolescence
3.2.1. Live-Attenuated Vaccines
3.2.2. Inactivated Vaccines
3.2.3. DNA Vaccines
3.2.4. RNA Vaccines
3.2.5. Subunit Vaccines
3.2.6. Vector Vaccines
3.3. Different Immunological Mechanisms after COVID-19 Vaccination
Vaccines | Manufacturers | Immune Response |
---|---|---|
mRNA - BNT162b2 - mRNA-1273 | - Pfizer/BioNTech + Fosun Pharma - Moderna + National Institute of Allergic and Infectious diseases | Expression of the viral S protein encoded in the mRNA and antigen presentation; induction of IFN I release, stimulating Th1 response, antibodies, and memory T and B cell generation |
Adenoviral Vectored - AZD122 (ChAdOx1-S) - Ad26.COV2 S - Sputnik V (rAd26-S + rAd5-S) | - AstraZeneca + University of Oxford - Janssen Pharmaceutical by Johnson & Johnson - Gamaleya Research Institute of Epidemiology and Microbiology | Emulation of viral infection; induces expression of IFN, antibodies, and memory T and B cells, along with T CD8 activity |
Inactivated - CoronaVac - Sinopharm - Covaxin - Valneva | Chinese Sinovac Biotech. BIBP B Bei**g BIBP and WIBP Indian Baharat Biotech French Biotechnology Com | Similar to adenoviral vectors; induction of IFN, memory T and B cells, antibody production, and T CD8 activity |
Protein Subunit - PREVENT-19 (NVX CoV-2373) | Novavax | Enhanced humoral responses and B and T memory cells |
Live-Attenuated - COVI-VAC | - Codagenix and Serum Institute of India | Induces antibody-based humoral and T lymphocyte-based cellular immune responses |
3.4. Vaccination of Children Aged 5–15 Years
3.5. Vaccination for Children Aged Less Than Five Years
3.6. Virology of SARS-CoV-2 and the Generated Immunity against Viral Components
3.6.1. Role of ACE Receptor Expression during COVID-19 Infection and Vaccination
3.6.2. Classes of Antibodies Produced in Response to COVID-19 Vaccines
3.6.3. Viral Mutations and Childhood Immunization
3.7. Safety of COVID-19 Vaccines for Infants and Children
3.7.1. Parental Hesitancy towards Vaccination of Their Children
3.7.2. Mechanisms of the Adverse Effects of Vaccination in Adults and Children
4. Immune Response to SARS-CoV-2 Infection
4.1. COVID-19-Generated Immunity in Neonates to Adolescents
Immunocompetent Cells | Immunological Elements | Functions |
---|---|---|
B cells | SARS-CoV-2 neutralizing antibodies | - Viral neutralization |
- Antibody-dependent cellular cytotoxicity (ADCC) | ||
- Antibody-dependent cellular phagocytosis (ADCP) | ||
- Complement activation (ADCA) [71,150,151,152,153,154,155,156] | ||
TFH cells | CD4-positive cells | - Interact with B cells to enhance survival and provide cellular help for antibody production [11,36,71,148,161] * |
CD4 Th1 T cells | IL-2, IFN-γ, and TNF-α | - CD8 T cell help, inflammation, and killing of virally infected cells |
CD4 Th2 T cells | IL-4, IL-5, and IL-13 | - B cell help and induction of antibody class-switching |
CD4 Th17 cells | IL-17A, IL-17F, IL-21, and IL-22 | - Inflammation via neutrophil recruitment and activation and innate cell activation |
CD4 Regulatory T cell (Treg) | IL-10 and TGF-β | - Suppression of inflammation and other T cells via cytokines or contact-dependent mechanisms |
CD8 cytotoxic T cells | Granzymes, perforin, IFN-γ, TNF-α, and FASL expression | - Killing of virally infected cells [29,44,45,46,47,48,63,71,74] |
4.2. Clinical Information Regarding COVID-19 in Children
4.3. Severe COVID-19 Immunopathology in Kids and Adults
4.3.1. Innate Immunity’s Function
4.3.2. The Role of Adaptive Immunity
The Cellular Components
The Humoral Response
4.3.3. Anamnestic Responses to SARS-CoV-2
4.3.4. Cytokine Storm
(A) [67,173,174,176,195] | ||||||
---|---|---|---|---|---|---|
Disease Severity | B Cells | Plasma Cells | IgG/IgA | B Cells | Plasma Cells | IgG/IgA |
(Adults) | (Children) | |||||
Severe/PIMS-Ts | ↓ | ↑ | ↑ ss | ↓ | ↓ | ↓ |
Mild | uc | ↑ | ↑ tr | uc | ↑ | ↑ |
Asymptomatic | uc | ↑ | ↑ tr | uc | ↑ | ↑ |
(B) [174,176,182,195] | ||||||
Disease Severity | CD3+ | CD8+ | CD4+ | CD8+ | CD8+ | CD4+ |
(Adults) | (Children) | |||||
Severe/PIMS-Ts | ↓ | ↓ | ↓ | ↓ | ↓ | ↓ |
Mild | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ |
Asymptomatic | uc | uc | uc | uc | un | un |
(C) [17,67,156,173,195] | ||||||
Disease Severity | Monocytes | Neutrophils | NK | Monocytes | Neutrophils | NK |
(Adults) | (Children) | |||||
Severe/PIMS-Ts | ↑ | ↑ | ↓ | ↓ | ↓ | ↓ |
Mild | ↑ | ↑ | ↓ | nr | nr | ↑ |
Asymptomatic | nr | nr | ↑ | nr | nr | ↑ |
4.3.5. PIMS-TS in Severe Pediatric COVID19
4.4. Energy Allocation Perspective on COVID-19 in Children
5. Concluding Immunological Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Neonates and Infants | Children to Young Adults | Information |
---|---|---|
Innate Immunity | Innate Immunity | References |
Poor neutrophil functions and muted innate immunity at birth | More mature immunity (fewer infections and effective vaccination) | [21,22,23] |
Reduced M/M functions | Waned maternal Ig | [24,25,26,27] |
Reduced bioactive molecules and tissue repair | Normal bioactive molecule production and tissue repair | [28] |
Fewer mDCs | Normal mDcs | [29] |
Reduced PcDcs (limited α/β interferon) | Normal PcDcs | [30] |
Low concentration of IL-12 | Normal IL-12 | [31] |
Normal TLR4, -7, and -9 | Normal LTR receptors | [30] |
Reduced NK activity (50% of adult level) | Increased NK activity | [32] |
Diminished concentration of alternative/lectin-binding complement pathways | Normal alternative/lectin-binding complementary pathways | [33] |
Adaptive Immunity | Adaptive Immunity | |
Maintained fetal Treg cells (self-tolerance) | Decreased Treg activity | [34,35,36,37] |
Predominant Th2 response | Strong CD4 and CD8 activity | [38] |
Enhanced γδ T cells (increased γ interferon production) | Increased CD45R naïve T cells | [39,40] |
B1 cell stimulation (increased interferon production) | B cell hypermutation and nonexposure cross-reactions | [41,42] |
B2 cell stimulation (IgM production) and short-lived plasma cells and Ig | Increased Ig production, increased plasma cells in the BM and retained antigens at the follicular DC | [41,43,44] |
Diminished Th1 and CD8 activity, enhanced T17 activity | Increased Th1, Th2, and Th17 numbers and activity | [45,46,47,48] |
Limited generation of B and T memory cells (limited hypermutation) | Generation of B and T memory cells, effective vaccination | [49,50,51,52,53,54,55,56,57,58] |
Limited involvement of the classical complement pathway (low CD21) | Increased classical complementary pathway activity | [59] |
Immunocompetent Cells | Immunological Elements | Functions |
---|---|---|
Dendritic cells (DCs) | Plasmacytoid (pDC) and myeloid (mDC) | - Antigen-presenting cells |
- mDC links innate immunity with adaptive immunity | ||
- pDC produces INF-α and INF-β upon viral exposure and expresses LTR7/9 [138,140] | ||
Neutrophils | Phagocytic cells | - Neutrophil activation is lower in pediatric COVID-19 [141] |
Monocyte–macrophages | Phagocytic cells | - Antigen-presenting cells to T cells |
- Recruitment of lymphocytes (elements of | ||
adaptive immunity) | ||
- Production of varieties of bioactive molecules | ||
- Activation of monocyte–macrophages enhanced via trained immunity [138,139,140] | ||
Natural killer (NK) cell | Granzymes, perforin, IFN-γ, TNF-α, and FASL expression | - Cytolytic granule-mediated cell apoptosis |
- Antibody-dependent cell-mediated cytotoxicity (ADCC) | ||
- Cytokine-induced NK and cytotoxic T lymphocyte (CTL) activation | ||
- Killing of virally infected cells (missing “self” hypothesis) | ||
- Brief decrease in NK cells after the onset of COVID-19 symptoms [138,140] | ||
Natural antibodies | Antibodies produced before viral infection or immunization | - Activation of the classical complement pathway |
- Antimicrobial activities [95,96] | ||
Alternative (properdin) complement pathway | C3 to C9 and other factors | - Part of the innate immunity |
- Does not require antibodies for activation [95,96] | ||
Epithelial and mucous membrane barriers | Mechanical barrier with protective armory | - Prevents microbial entrance |
- Virus must attach to it before entrance [95,138] |
Adults | Children | |||||
---|---|---|---|---|---|---|
Severe | Mild | Asymptomatic | PIMS-TS | Severe | Mild | Asymptomatic |
↑ IL-6 | ↑ IL-6 | ↔ IL-6 | ↑ IL-6 | ↔ IL-6 | ↔ IL-6 | ↔ IL-6 |
↑ IL-10 | ↑ IL-10 | ↑ IL-10 | ↑ IL-10 | ↑ IL-10 | ↑ IL-10 | ↑ IL-10 |
↑ IFN | ↑ IFN | ↔ IFN | ↑ IFN | ↑/↔ IFN | ↑/↔ IFN | ↔ IFN |
↑ TNF-α | ↑ TNF-α | ↔ TNF-α | ↑ TNF-α | ↔ TNF-α | ↔ TNF-α | ↔ TNF-α |
↑/↔ IL-1β | ↑/↔ IL-1β | ↔ IL-1β | n/a | ↔ IL-1β | ↔ IL-1β | ↔ IL-1β |
↑/↔ IL-8 | ↑/↔ IL-8 | ↔ IL-8 | ↑ IL-8 | ↑ IL-8 | ↔ IL-8 | ↔ IL-8 |
↑/↔ IL-17 | ↑/↔ IL-17 | ↔ IL-17 | ↑ IL-17 | ↑/↔ IL-17 | ↑/↔ IL-17 | ↔ IL-17 |
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Abdulla, Z.A.; Al-Bashir, S.M.; Alzoubi, H.; Al-Salih, N.S.; Aldamen, A.A.; Abdulazeez, A.Z. The Role of Immunity in the Pathogenesis of SARS-CoV-2 Infection and in the Protection Generated by COVID-19 Vaccines in Different Age Groups. Pathogens 2023, 12, 329. https://doi.org/10.3390/pathogens12020329
Abdulla ZA, Al-Bashir SM, Alzoubi H, Al-Salih NS, Aldamen AA, Abdulazeez AZ. The Role of Immunity in the Pathogenesis of SARS-CoV-2 Infection and in the Protection Generated by COVID-19 Vaccines in Different Age Groups. Pathogens. 2023; 12(2):329. https://doi.org/10.3390/pathogens12020329
Chicago/Turabian StyleAbdulla, Zainalabideen A., Sharaf M. Al-Bashir, Hiba Alzoubi, Noor S. Al-Salih, Ala A. Aldamen, and Ahmed Z. Abdulazeez. 2023. "The Role of Immunity in the Pathogenesis of SARS-CoV-2 Infection and in the Protection Generated by COVID-19 Vaccines in Different Age Groups" Pathogens 12, no. 2: 329. https://doi.org/10.3390/pathogens12020329