COVID-19 Epidemiology, Immunity, and Vaccine Development in Children: A Review
Abstract
:1. Introduction
2. COVID-19 in Children and Adolescents
2.1. Epidemiology
2.2. Clinical Manifestations
2.3. Transmission
2.4. Immune Response
3. Pediatric COVID-19 Vaccine Development
3.1. Pediatric Clinical Trials
3.1.1. Clinical Trial Data on Immunogenicity and Vaccine Efficacy
3.1.2. Clinical Trial Safety Data
3.2. Real-World Evidence
3.2.1. Real-World Vaccine Effectiveness
3.2.2. Real-World Safety
3.2.3. Myocarditis and Pericarditis
3.3. Vaccination Recommendations
3.4. Parental Vaccine Hesitancy
CDC [83] | JCVI [84,85,86,87,95] | WHO [14] | |||||
---|---|---|---|---|---|---|---|
Children 6 Months–4 Years Old | Children 5–11 Years Old | Adolescents 12–17 Years Old | Children 5–11 Years Old | Adolescents 12–17 Years Old | Children 5–11 Years Old | Adolescents 12–17 Years Old | |
Primary vaccination | Recommended for all individuals Dosing: three 3 µg BNT162b2 doses (≥3 weeks between doses 1 and 2 and ≥8 weeks between doses 2 and 3); two 25 µg mRNA-1273 doses (≥4–8 weeks between doses) | Recommended for all individuals Dosing: two 10 µg BNT162b2 doses ≥3–8 weeks apart for those 5–11 years old; two 25 µg mRNA-1273 doses ≥4 weeks apart for those 5 years old; and two 50 µg mRNA-1273 doses ≥4–8 weeks apart for those 6–11 years old | Recommended for all individuals Dosing: two 30 µg BNT162b2 doses ≥3–8 weeks apart; two 100 µg mRNA-1273 doses ≥4–8 weeks apart | Should be offered to those in a clinical risk group or household contacts of immunosuppressed individuals Dosing: two 10 µg BNT162b2 doses 8 weeks apart | Should be offered to all individuals Dosing: two 30 µg BNT162b2 doses ≥8 (at-risk individuals) or ≥12 weeks (healthy individuals) apart | Countries should consider their specific epidemiologic and social context when considering vaccination of children and adolescents, with priority given to vaccination of adults and at-risk groups | |
Additional dose | No recommendations given | Recommended for moderately and severely immunocompromised individuals Timing: ≥28 days after second dose | Not recommended | Should be offered to those who were severely immunosuppressed at the time of their first or second dose Timing: generally ≥8 weeks after second dose | No recommendations given | No recommendations given | |
Booster dose | Not recommended | Recommended (for BNT162b2 only) Timing: ≥5 months after last primary dose | Recommended (for BNT162b2 only) Timing: ≥5 months after last primary dose | Not recommended | 12–15 years of age: should be offered to those in a clinical risk group, household contact of immunosuppressed individuals, or severely immunocompromised and received a third dose 16–17 years of age: should be offered to all individuals Timing: ≥3 months after last primary dose | No recommendations given | No recommendations given |
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Vaccine (Type) | Characteristic | Details |
---|---|---|
Infants, children, and adolescents | ||
CoronaVac (inactivated vaccine) [49] | ClinicalTrials.gov identifier | NCT04551547 |
Phase (design) | 1/2 (randomized, controlled) | |
Age group | 3–17 years | |
Dose (schedule) | 1.5 or 3.0 µg (2 doses 28 days apart) | |
Number of participants | 72 (phase 1) and 480 (phase 2) | |
Immunogenicity | Humoral responses were induced, with neutralizing antibody titers induced by the 3.0 µg dose higher than those of the 1.5 µg dose (the data support the 3.0 µg dose for further development in this age group) | |
Safety | The most common reactions were injection site pain and fever; most were mild or moderate and transient | |
CoronaVac (inactivated vaccine) | ClinicalTrials.gov identifier | NCT04992260 |
Phase (design) | 3 (randomized, placebo-controlled) | |
Age group | 6 months–17 years | |
Number of participants | ~14,000 | |
Endpoints | Efficacy of RT-PCR–confirmed symptomatic COVID-19 (primary), safety, immunogenicity | |
Primary completion date | May 2022 (estimated) | |
BBIBP-CorV (inactivated vaccine) [50] | Clinical trial identifier | ChiCTR2000032459 |
Phase (design) | 1/2 (randomized, controlled) | |
Age group | 3–17 years | |
Dose (schedule) | 2, 4, or 8 µg (3 doses on days 0, 28, and 56) | |
Number of participants | 288 (phase 1) and 720 (phase 2) | |
Immunogenicity | All doses elicited robust humoral responses; the 4 µg dose on a 2-dose regimen (21 days apart) will be further studied in this age group | |
Safety | The most common reactions were injection site pain and fever; most were mild or moderate | |
Adolescents | ||
BNT162b2 (mRNA vaccine) [46] | ClinicalTrials.gov identifier | NCT04368728 |
Phase (design) | 3 (randomized, placebo-controlled) | |
Age group | 12–15 years | |
Dose (schedule) | 30 µg (2 doses 21 days apart) | |
Number of participants | 2260 | |
Follow-up | At the time of the report, 58% of participants had ≥2 months of follow-up after dose 2 | |
Vaccine efficacy | Observed vaccine efficacy of 100% (95% CI: 75.3, 100) | |
Immunogenicity | Immune response was noninferior to that observed in 16–25-year-olds | |
Safety | Injection site pain was the most common local reaction, and headache and fatigue were the most common systemic events; these events were mostly mild to moderate in severity and transient | |
mRNA-1273 (mRNA vaccine) [48] | ClinicalTrials.gov identifier | NCT04649151 |
Phase (design) | 2/3 (randomized, placebo-controlled) | |
Age group | 12–17 years | |
Dose (schedule) | 100 µg (2 doses 28 days apart) | |
Number of participants | 3726 | |
Follow-up | 83 days | |
Vaccine efficacy | Using CDC definition of COVID-19 with onset of 14 days after dose 2: 93% (95% CI: 47.9, 99.9) In the per-protocol population with an onset of 14 days after dose 2: 56% (95% CI: 16.8, 76.4) | |
Immunogenicity | Immune response was noninferior to that observed in 18–25-year-olds | |
Safety | Injection site pain was the most common local reaction, and fatigue and headache were the most frequently reported systemic events; these were most commonly grade 1/2 and transient | |
Children | ||
BNT162b2 (mRNA vaccine) [47] | ClinicalTrials.gov identifier | NCT04816643 |
Phase (design) | 2/3 (randomized, placebo-controlled) | |
Age group | 5–11 years | |
Dose (schedule) | 10 µg (2 doses 21 days apart) | |
Number of participants | 2268 | |
Follow-up | Median of 2.3 months (range 0–2.5 months) | |
Vaccine efficacy | Observed vaccine efficacy of 90.7% (95% CI: 67.7, 98.3) | |
Immunogenicity | Immune response was noninferior to that observed in 16–25-year-olds | |
Safety | Injection-site pain was the most common local reaction, and fatigue and headache were the most frequently reported systemic events; these events were mostly mild to moderate in severity and transient | |
mRNA-1273 (mRNA vaccine) [64] | ClinicalTrials.gov identifier | NCT04796896 |
Phase (design) | 2/3 (randomized, placebo-controlled) | |
Age group | 6–11 years | |
Dose (schedule) | 50 µg (2 doses 28 days apart) | |
Number of participants | 4016 | |
Follow-up | Median 82 days after dose 2 | |
Vaccine efficacy | Using CDC definition of COVID-19 with onset of 14 days after dose 2: 88% (95% CI: 70.0, 95.8) | |
Immunogenicity | Immune response was noninferior to that observed in 18–25-year-olds who received 2 doses at the 100 µg dose level | |
Safety | The most common local adverse reaction was injection site pain, and the most common systemic adverse reactions were headache and fatigue | |
Infants | ||
BNT162b2 (mRNA vaccine) [57] | ClinicalTrials.gov identifier | NCT04816643 |
Phase (design) | 2/3 (randomized, placebo-controlled) | |
Age group | 6 months–4 years | |
Dose (schedule) | Dose 1 and 2 administered 3 weeks apart; dose 3 administered ≥8 weeks after dose 2 | |
Number of participants | 1776 (6–23 months of age); 2750 (2–4 years of age) | |
Follow-up | Median 1.3–1.4 months after dose 3 | |
Vaccine efficacy | N/A | |
Immunogenicity | Immune response after 3 doses was noninferior to that observed after 2 doses in 16–25-year-olds | |
Safety | In participants 6–23 months of age, adverse reactions after any dose included irritability (68%), decreased appetite (39%), injection site tenderness (26%), injection site redness (18%), fever (14%), injection site swelling (7%), and lymphadenopathy (0.2%). In participants 2–4 years of age, these included injection site pain (47%), fatigue (45%), injection site redness (19%), fever (11%), headache (9%), injection site swelling (8%), chills (6%), muscle pain (5%), joint pain (2%), and lymphadenopathy (0.1%). | |
mRNA-1273 (mRNA vaccine) [61] | ClinicalTrials.gov identifier | NCT04796896 |
Phase (design) | 2/3 (randomized, placebo-controlled) | |
Age group | 6 months–5 years | |
Dose (schedule) | 25 µg (2 doses 1 month apart) | |
Number of participants | 6388 | |
Follow-up | Median of 68–71 days after dose 2 | |
Immunogenicity | Immune response was noninferior to that observed in 18–25-year-olds who received 2 doses at the 100 µg dose level | |
Safety | The most common adverse reactions in those 6–23 months of age were irritability/crying (64–68%), pain (37–46%), sleepiness (35–37%), and loss of appetite (30–32%). In those 24–36 months of age, these were pain (53–68%), irritability/crying (54–55%), and sleepiness (24–31%). In those 37 months–5 years of age, these were pain (65–73%) and fatigue (40–48%). |
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Fergie, J.; Moran, M.M.; Cane, A.; Pather, S.; Türeci, Ӧ.; Srivastava, A. COVID-19 Epidemiology, Immunity, and Vaccine Development in Children: A Review. Vaccines 2022, 10, 2039. https://doi.org/10.3390/vaccines10122039
Fergie J, Moran MM, Cane A, Pather S, Türeci Ӧ, Srivastava A. COVID-19 Epidemiology, Immunity, and Vaccine Development in Children: A Review. Vaccines. 2022; 10(12):2039. https://doi.org/10.3390/vaccines10122039
Chicago/Turabian StyleFergie, Jaime, Mary M. Moran, Alejandro Cane, Shanti Pather, Ӧzlem Türeci, and Amit Srivastava. 2022. "COVID-19 Epidemiology, Immunity, and Vaccine Development in Children: A Review" Vaccines 10, no. 12: 2039. https://doi.org/10.3390/vaccines10122039
APA StyleFergie, J., Moran, M. M., Cane, A., Pather, S., Türeci, Ӧ., & Srivastava, A. (2022). COVID-19 Epidemiology, Immunity, and Vaccine Development in Children: A Review. Vaccines, 10(12), 2039. https://doi.org/10.3390/vaccines10122039