Next Article in Journal
Vaccine Coverage and Effectiveness in a School-Based Varicella Outbreak in Jinan Prefecture, Shandong Province
Next Article in Special Issue
Increased Mild Vaccine-Related Side Effects and Higher Specific Antibody Titers in Health Care Workers with Previous SARS-CoV-2 Infection after the mRNA BNT162b2 Vaccine
Previous Article in Journal
COVID-19 Vaccine Booster Strategies for Omicron SARS-CoV-2 Variant: Effectiveness and Future Prospects
Previous Article in Special Issue
Relative Vaccine Effectiveness of the Third Dose of CoronaVac or BNT162b2 Following a Two-Dose CoronaVac Regimen: A Prospective Observational Cohort Study from an Adult Vaccine Center in Turkey
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Vaccines
Volume 10
Issue 8
10.3390/vaccines10081224
vaccines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Cross-Sectional Survey on BNT162b2 mRNA COVID-19 Vaccine Serious Adverse Events in Children 5 to 11 Years of Age: A Monocentric Experience

by
Silvia Bloise
*,
Alessia Marcellino
,
Beatrice Frasacco
,
Pietro Gizzone
,
Claudia Proietti Ciolli
,
Vanessa Martucci
,
Mariateresa Sanseviero
,
Emanuela Del Giudice
,
Flavia Ventriglia
and
Riccardo Lubrano
Dipartimento Materno Infantile e di Scienze Urologiche, Sapienza Università di Roma, UOC di Pediatria e Neonatologia-Polo Pontino, 04100 Latina, Italy
*
Author to whom correspondence should be addressed.
Vaccines 2022, 10(8), 1224; https://doi.org/10.3390/vaccines10081224
Original submission received: 21 June 2022 / Revised: 27 July 2022 / Accepted: 28 July 2022 / Published: 30 July 2022
(This article belongs to the Special Issue Prevention of SARS-CoV-2 Infection and COVID-19: Safety, Immunogenicity and Effectiveness of Available Vaccines)
Browse Figures
Review Reports Versions Notes

Abstract

:
Objective: Our aim was to evaluate the safety of COVID-19 vaccine in children resident in the Latina Local Health Authority. Methods: We conducted a telephone survey among children aged 5–11 years receiving BNT162b2 mRNA COVID-19 vaccine between December 15 and 21. The main outcomes included the presence of allergic reactions or anaphylaxis, adverse events after 24–48 h, 7 and 20 days of taking the first and second doses of medications, and documented SARS-CoV-2 infection after vaccination. The information obtained was automatically linked to a spreadsheet and analyzed. Results: 569 children were enrolled. The mean age was 114 ± 4.24 months; there were 251 males in the study. The vaccine showed a favorable safety profile; no anaphylaxis or serious adverse events were reported. The most common symptoms both after the first and second dose were injection site reactions, asthenia, and headache. Injection site reactions were more frequent after the first dose (p = 0.01), while systemic symptoms were more frequent after the second dose (p = 0.022). These symptoms were more frequent in patients with comorbidities (p = 0.0159). Conclusion: Our findings confirm the safety of COVID-19 vaccine in children younger 11 years and could be useful to promote its diffusion in pediatric ages in order to achieve “herd immunity” and prevent the virus’s circulation.

1. Introduction

Two years after the onset of the pandemic, about 567 million cases of COVID-19 have already been reported worldwide and their increase in the last months has been an expression of the fifth wave of the SARS-CoV-2 [1,2,3,4].
The development and testing of vaccines against COVID-19 has been very rapid. In fact, already in the first half of 2021 many vaccines with different mechanisms of action were introduced in many countries. The efficacy of these vaccines has been demonstrated through phase 3 clinical trials [5,6,7,8,9,10,11,12]. These data are important, but to establish the true effectiveness of a vaccine it is necessary to assess the impact on the general population (that is, the reduction in the risk of infection and disease among vaccinated people) [13,14].
Since the introduction of the vaccine campaign, many reports have shown promising results with reductions in the incidence of infection, hospitalizations, and deaths in different countries [15,16,17,18,19,20,21,22,23,24]. Specifically, in Italy, according to data from the Istituto Superiore di Sanità, thanks to vaccination there have been more than 500,000 hospitalizations, more than 55,000 ICU admissions, and about 150,000 deaths avoided [25].
To date, the vaccination of the global population seems to be the only effective strategy to achieve the “herd immunity” and consequently prevent the virus’s circulation [26,27]. This requires the entire population to be vaccinated, including children and adolescents. In addition, since antibody response against SARS-CoV-2 has been shown to wane over time, more booster doses are needed [28,29,30,31].
Until December 2021, vaccination has been authorized for COVID-19 prevention from the age of 11 years [32,33]. On 7 December 2021 the authorization was expanded to include children aged from 5 to 11 years [34,35,36,37]. Vaccinating this second age group could help, in association with the implementation of preventive measures in children [38,39,40,41], to mitigate downstream effects of the pandemic, such as social isolation and disruption of education, and allow for a return to normal life. However, the issue of vaccination in the pediatric age group has been very debated and there is still a lot of fear and perplexity among parents and pediatricians. Therefore, it is important to assess carefully the risks and benefits of the vaccination in children [42] and in order to justify childhood vaccination, it is necessary an effort by the scientific community to report all experiences and possible adverse events related to the vaccine. This could improve community knowledge about this topic, debunking numerous fake news and increasing the compliance and consent of caregivers. In this context, we have conducted a cross-sectional survey at our center on the effects of BNT162b2 mRNA COVID-19 vaccine administered to children 5 to 11 years old. The primary aim was to evaluate the safety of the vaccine through the assessment of adverse events reported by parents 24-48 h, 7 days, and 20 days after the first and the second dose. The secondary aim was to evaluate the difference between first and second dose in terms of tolerability. The tertiary aim was to evaluate the difference in incidence of SARS-CoV-2 infection with an onset of seven days after first and second dose between the vaccinated and unvaccinated pediatric population residing in the Local Health Authority (ASL) of Latina.

2. Materials and Methods

This was a prospective, cross-sectional study conducted by the Pediatric Unit of Santa Maria Goretti Hospital, in Latina—Sapienza University of Rome (Polo Pontino) from 15 December 2021 to 31 January 2022. The Institutional Review Board of the Maternal and Child Health Department of the Local Health Authority of Latina approved the study protocol. This report follows the STROBE reporting guideline for cross-sectional studies.
We included all children aged 5–11 years undergoing first dose of vaccination with BNT162b2 mRNA COVID-19 vaccine between December 15 and 21. The exclusion criterion was previous SARS-CoV-2 infection within three months prior to the date of initiation of vaccination and an age greater than 11 years old or less than 5 years old. The vaccination protocol included two doses of vaccine spaced 21 days apart. In addition, only a single dose of vaccine was provided for children who had been previously infected for less than 12 months [43]
At the time of vaccination, parents gave written consent to receive the vaccine and were informed that they would be contacted by a doctor in our department to check for any side effects after vaccination.
We developed a survey with a web-form link to collect data (Google forms). The survey was conducted through a questionnaire administered, after a verbal informed consent, by telephone by the doctors of the department of pediatrics of Santa Maria Goretti Hospital to parents of children 5–11-years-old undergoing vaccination with BNT162b2 mRNA COVID-19 vaccine between December 15 and 21.
The questionnaire included specific questions: children’s demographic characteristics, comorbidities, previous SARS-CoV-2 infection and clinical course, presence of allergic reactions or anaphylaxis after first and second doses, presence of adverse events after 24–48 h, 7 days and 20 days, after the first and second doses and any medications taken for these symptoms, and documented SARS-CoV-2 infection after vaccination.
The information obtained was automatically linked to a spreadsheet and analyzed.
To evaluate the difference in incidence of SARS-CoV-2 infection between the vaccinated and unvaccinated children of the ASL of Latina, we considered two time periods: the first from seven days after the first dose (December 22) to January 4; and the second from seven days after the second dose (January 12) to January 31. Then, we compared the number of children infected in the unvaccinated group and in the vaccinated group in the two time periods of study.

Statistical Analysis

The statistical analysis was performed with JMP® 16.1.0 program for Mac (SAS Institute Inc., Rome, Italy). The qualitative variables were described as the distribution of absolute frequencies and percentages. We used Fisher’s test to compare categorical variables and Chi square with Yates’ correction. A p value < 0.05 was considered significant.

3. Results

3.1. Clinical and Demographic Characteristics of Patients

We enrolled 569 children 5-11 years old receiving the BNT162b2 vaccine between 15 December 2021 to 11 January 2022. The mean age was 114 ± 4.24 months; 251 of these individuals were male.
Eighty-point-seven-percent of patients had no comorbidity, while nineteen-point three-percent had comorbidity (46% allergies, 24% asthma, 9% gastrointestinal diseases, 8% heart diseases, 7% neurological diseases 3% nephrological diseases, 2% rheumatological diseases, 1% other diseases).
Ninety-three-point-three percent of patients had not experienced SARS-CoV-2 infection at the time of vaccination, while six-point-four percent had a positive history of previous SARS-CoV-2 infection. Of these last few, forty-one-point-seven percent of children were asymptomatic, while fifty-eight-point-three percent showed mild symptoms. The most common symptoms of previous infection were: fever (71.4%), upper respiratory symptoms (42.8%), headache (33.4 %), gastrointestinal symptoms (14.2%), asthenia (9.5%), and arthralgias (4.8%).
The clinical and demographic characteristics are summarized in Table 1.

3.2. Adverse Events 24–48 h after First Dose

24–48 h after the first dose, sixty point one of participants reported local and/or systemic events and thirty-nine- point nine percent had no symptoms. The most common symptoms reported were: injection site reactions (95.6%), mainly pain (90.4%), redness (2.3%), swelling (2.9%) and induration of the site (0.2%). Systemic adverse effects were: asthenia (10.8%), headache (8.1%), gastrointestinal symptoms (4%), fever (2.9%), arthromyalgia (2.6%), lymphadenopathy (1.4%), irritability (1.7%), drowsiness (1.4%), epistaxis (0.29%), and paresthesias of the limbs (0.3%).
No thromboses or hypersensitivity adverse events or vaccine-related anaphylaxis were seen.
Detailed graphical representation of symptoms experienced after first dose of BNT162b2 mRNA COVID-19 vaccine is shown in Figure 1.
Local and systemic events were mild and typically resolved within a few days (12–24 h: 42.2 %; 12 h: 30.2 %; 24–48 h: 20.2 %; 48–72 h: 7.3 %).
Only twenty-four -point four percent of children took medications for these symptoms. The most commonly used medications were: acetaminophen (84.1 %), non-steroidal anti-inflammatory drugs (7.3%), and local topical creams (9.7%).

3.3. Adverse Events 7 Days after First Dose

Only one point nine percent of children experienced symptoms seven days after the first dose, while ninety-eight-point-one percent showed no symptoms. The symptoms reported were: persistence of pain at the injection site (50%), headache (20%), fever (20%), and asthenia (10%). The duration of these symptoms was: 12–24 h: 66.7%; 12 h: 11.1%; 48–72 h: 22.2%.
Thirty-three-point-three percent of children took medications for these symptoms. The most commonly used medications were: acetaminophen (66.7%), non-steroidal anti-inflammatory drugs (33.3%), and local topical creams (33.3%).
Seven days after first dose, there were twenty-seven (5.4%) cases of COVID-19 infection confirmed by molecular swab.
The infection was symptomatic in sixty -point seven percent of cases and asymptomatic in thirty-nine- point three percent of cases. The symptoms reported were mild and were fever (52.9%), headache (47%), upper respiratory symptoms (41.1%), gastrointestinal symptoms (11.7%), asthenia (11.7%), and arthralgias (11.7%).

3.4. Adverse Events 20 Days after First Dose

Ninety-nine-point-six percent of children not experienced symptoms 20 days after the first dose; Only two children (0.4%) experienced symptoms 20 days after the first dose. The symptoms were inappetence and intercostal pain. These symptoms were mild with spontaneous resolution in 48–72 h.

3.5. Adverse Events 24–48 h after Second Dose

Of the 569 children enrolled, 449 underwent the second dose and were surveyed, 49 did not undergo the second dose, and 71 did not answer the phone and did not complete the survey (Figure 2-flowchart).
The main reasons for not performing the second dose were: SARS-CoV-2 infection after the first dose (54.1%), quarantine status due to contact with positive subjects (25%), previous natural infection in the six months prior to vaccination (18.7%), fever from other causes (2%).
At 24–48 h after the second dose, fifty-one-point two percent of participants reported local and/or systemic events and forty-eight point eight had no symptoms. The most common symptoms reported were injection site reactions (95.8%), mainly pain (81.7%), redness (7.1%), swelling (6.2%) and induration of the site (1.25%). Systemic adverse effects were: asthenia (15.9%), headache (14.2%), fever (8.36%), gastrointestinal symptoms (6.27%), arthromyalgia (2.9%), linfoadenopatia (2.5%), shivers (1.6%), and irritability (0.8%),
No thromboses or hypersensitivity adverse events or vaccine-related anaphylaxis were seen after the second dose.
Detailed graphical representation of symptoms experienced after the second dose of BNT162b2 mRNA COVID-19 vaccine is shown in Figure 3.
Local and systemic events were mild and typically resolved within a few days (12–24 h: 43.8%; 12 h: 24.2%; 24–48 h: 22.5%; 48–72 h: 9.6%).
Only twenty-five-point-six percent of children took medications for these symptoms. the most commonly used medications were: acetaminophen (78.6%), non-steroidal anti-inflammatory drugs (11.4%), and local topical creams (11.4%).
No differences in reactogenicity were noted between participants who were SARS-CoV-2–positive at baseline and those who were SARS-CoV-2–negative at baseline (p = 0.86).
We found a difference between patients with comorbidities than healthy patients. In particular, the adverse events were more frequent in patients with comorbidities (p = 0.0159). Local and systemic events were always mild and the most common symptoms reported were the following: injection site reactions (53.7%) asthenia (5.5%), headache (3.7%), fever (1.8%), gastrointestinal symptoms (1.8%), irritability (1.8%),

3.6. Adverse Events 7 Days after Second Dose

Only zero-point-eight percent of children experienced symptoms seven days after the first dose, while ninety-nine-point-two percent showed no symptoms. The symptoms reported were: headache (50%), cough (25%) and lymphadenopathy (25%).
The duration of these symptoms was: 12–24 h: 25%; 24–48 h 25%; 48–72 h: 50%.
One-point-three percent of children took medications for these symptoms. The medication used was paracetamol acetaminophenin one hundred percent of cases.
Seven days after first dose, there were no cases of COVID-19 infection.

3.7. Adverse Events 20 Days after Second Dose

No children experienced symptoms 20 days after the second dose.
20 days after second dose, there were no cases of COVID-19 infection.
Difference in tolerability between first and second dose
We found some differences in reactogenicity between the two doses of BNT162b2 (p = 0.021).
In particular, injection site reactions were more frequent after the first dose (p = 0.01), while systemic symptoms such as fever was more frequent after the second dose (p = 0.022).
In contrast, there were no differences regarding other symptoms: Asthenia (p=0.27), headache (p = 0.11), arthromyalgia (p = 1), gastrointestinal symptoms (p = 0.45, lymphadenopathy (p = 1), drowsiness (p = 0.07), and irritability (p = 1).

3.8. Difference in Incidence of SARS-CoV-2 Infection between Unvaccinated and Vaccinated Children

In the ASL of Latina there are 37,003 resident children aged 5–11 years. In the period between December 22 and January 4, 538 of the unvaccinated children became infected, while only 27 of the 565 vaccinated children contracted the SARS-CoV-2 infection (p < 0.0001). In the period between January 12 and January 31, 3475 of the unvaccinated children became infected, while none of vaccinated children contracted the SARS-CoV-2 infection.

4. Discussion

4.1. Safety of COVID-19 Vaccine in Children 5–11 Years

Our results show that the vaccine BNT162b2 mRNA has a good safety profile in the 5–11-year-old age group. These findings are similar to the safety data reported from preauthorization trials for m-RNA vaccines COVID-19 in pediatric ages [44,45]. In fact, in our study, the most frequently symptoms reported was injection site pain, while the most frequently reported systemic events were fatigue and headache and systemic reactions (fever was more frequently reported after dose 2). All adverse events reported were mostly mild with resolution in one to two days. Furthermore, no differences in reactogenicity were noted between participants with previous SARS-CoV-2 infection. Our data are also in line with other recent reports conducted since the introduction of the vaccination in the 5–11-years age group [46,47,48]. In particular, Hause et al. [49] have analyzed data from three United State vaccine safety surveillance systems in the first four months after COVID-19 vaccine recommendations in this age group. In this report, among the 48,795 children enrolled, most reported reactions were mild-to-moderate, most frequently described the day after vaccination, and were more common after dose 2. The most common symptoms described were injection site pain, fatigue, headache, fever, and myalgia. No serious adverse events, such as myocarditis, occurred in our study. Myocarditis is a rare, but serious adverse event reported after COVID-19 vaccination (especially in adolescent males and young adult men) [50]. However, for children 5 to 11-years-old this condition was rarely reported after vaccination and reporting rates were lower than for older children comparable to the risk rate of the general population [51,52]. Finally, we found that patients with comorbidities had more adverse events than healthy patients. However, the reactions described were always mild, not interfering with normal daily activities, and no serious adverse events were reported. Therefore, we believe that vaccination should be promoted especially in these patients [53,54], who could be at higher risk of severe forms of COVID-19 [55,56].

4.2. Viral Variants and Vaccine Efficacy in Pediatric Age

Another concern about the pediatric COVID-19 vaccine is related to its efficacy against new SARS-CoV-2 variants. Data regarding this topic are still few and conflicting. Recently, Sacco and colleagues [57] described the effectiveness of BNT162b2 in children aged 5–11 years after the onset of the omicron variant (B.1.1.529) in Italy. The authors reported an adjusted vaccine effectiveness against infection of 29.4% in fully vaccinated and 27.4% in partially vaccinated children, with a decreasing trend at a distance after vaccination. Similar results have been shown in a study conducted on data from New York, in which vaccine effectiveness against infection in children aged 5–11 years decreased from 65% during the first 2 weeks after two doses to 12% after 28–34 days [58]. In a recent study, Chen et al. have studied the antibody response against the omicron variant in vaccinated children and children with SARS-CoV-2 infection, showing that only 38.2% of BNT162b2 vaccine recipients and 26.7% of recovered COVID-19 patients had neutralizing antibody serum titers, concluding finally that the pediatric age group will likely be more susceptible to vaccine breakthrough infections or reinfections due to the omicron variant than previous variants [59]. On the other hand, however, data from samples of adults are more encouraging. Lauring and others authors, in a study conducted on 11,690 patients, showed that mRNA vaccines were found to be highly effective in preventing COVID-19 associated hospital admissions related to the alpha, delta, and omicron variants. In particular, it was necessary to receive three doses of vaccines to achieve the same protection against omicron variant compared with two doses needed for the other variants [60]. Furthermore, in a recent study published in New England [61], the authors described the data based on 1185 children enrolled, showing that although two doses of vaccine results in lower protection against the omicron variant than the delta variant. However, this reduces the risk of critical illness caused by both variants also in pediatric age. Therefore, we believe that in view of the good safety profile of the vaccine in the age group of 5–11 years and the positive impact on hospitalizations and risk of critical illness (even during the period of the omicron variant), vaccination should continue to be promoted in this age group. Certainly, further studies are essential to confirm these data and especially to assess whether more booster doses are needed in the pediatric age group to achieve more effective and long-lasting protection [62].

4.3. Benefits of COVID-19 Vaccination in the Pediatric Age Group

We believe that the vaccination of BNT162b2 in children 5–11 years old is important for several reasons. Primarily, on the basis of mathematical models it has been demonstrated that vaccination against COVID-19 in children aged 5–11 years old leads to a significant reduction in the number of infections and, to a lesser extent, in the number of hospitalizations and deaths, with a reduction in the spread of coronavirus by up to 16% [63]. In fact, in our study, we demonstrated early protection already after a single dose and the absence of infection with a two-dose regimen in vaccinated children compared with unvaccinated children of the same age group. Vaccinating children will bring us closer to mass vaccination and consequently to the achievement of herd immunity, protecting in this way the most vulnerable population groups. In fact, it has been demonstrated that children’s transmission to household members is high and is similar to that from adults [64,65,66]. Second, despite in the pediatric age COVID-19 morbidity and mortality are significantly lower than in adults [67,68], children can also be at risk of developing post-COVID-19 complications, such as long COVID syndrome and multisystem inflammatory syndrome (MIS-C) [69,70,71]. Related to this, different reports in adults showed a decrease in disease complication rate COVID-19 in vaccinated people supporting the importance of the vaccination also in this age group [72]. Furthermore, MIS-C also appears to be much rarer in children and adolescents fully vaccinated [73,74]. Last but not least, children represent the category more susceptible to the indirect effects of the pandemic [75]. In fact, the closure of the school and of other extracurricular activities has caused an important psychosocial harm to children and especially adolescents during these years [76,77]. Therefore, the implementation of vaccines in this age group could enable children to re-engage in their world with positive effects on their psychophysical and relational development. But despite the fact that the beneficial effects of prevention of SARS-CoV-2 infection to seem to outweigh the potential risks of the vaccination in pediatric ages as well, there is still a low intention by parents to vaccinate their children (mainly due to fear of the side effects of vaccination) [78].

4.4. Limitations of the Study

This report is subject to some limitations (primarily the low sample size and the short surveillance period). Second, we also acknowledge that symptoms were only reported through an online survey rather than directly ascertained and are related to a single-center of study. Finally, we did not compare the differences in clinical outcomes of vaccinated and unvaccinated patients who contracted SARS-CoV-2 infection.

4.5. Conclusions

Pediatric vaccination with COVID-19 is recent, and vaccine hesitancy among parents of children aged 5–11 years is still high (despite the increase of COVID-19 cases even in this age group in recent months). Our findings support the data available in the literature on COVID-19 vaccination in children, showing a good safety profile of m-RNA vaccine in healthy children and those with comorbidities. We believe our data could be useful to reassure parents and promote pediatric vaccination. Certainly, further studies are needed to evaluate the efficacy of COVID-19 vaccine in children aged 5–11 years and the degree of protection against new variants

Author Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by S.B., A.M., V.M., M.S., E.D.G., B.F., P.G., C.P.C., F.V. and R.L. The first draft of the manuscript was written by S.B. and all authors commented on previous versions of the manuscript. R.L. and F.V. conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Institutional review board of Maternal and Child Health Department of the Local Health Authority of Latina approved the study protocol.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. COVID-19-Situazione nel Mondo-Ministero della Salute. WHO Coronavirus (COVID-19) Dashboard. Available online: https://www.salute.gov.it/portale/nuovocoronavirus/dettaglioContenutiNuovoCoronavirus.jsp?area=nuovoCoronavirus&id=5338&lingua=italiano&menu=vuoto (accessed on 23 July 2022).
  2. Aouissi, H.A. Algeria’s preparedness for Omicron variant and for the fourth wave of COVID-19. Glob. Health Med. 2021, 3, 413–414. [Google Scholar] [CrossRef]
  3. Aleem, A.; Akbar Samad, A.B.; Slenker, A.K. Emerging Variants of SARS-CoV-2 And Novel Therapeutics against Coronavirus (COVID-19); StatPearls Publishing: Treasure Island, FL, USA, 2022. [Google Scholar]
  4. Kannan, S.; Shaik, S.A.P.; Sheeza, A. Omicron (B.1.1.529)-variant of concern-molecular profile and epidemiology: A mini review. Eur. Rev. Med. Pharm. Sci. 2021, 25, 8019–8022. [Google Scholar] [CrossRef]
  5. Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef]
  6. Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef]
  7. Voysey, M.; Costa Clemens, S.A.; Madhi, S.A.; Weckx, L.Y.; Folegatti, P.M.; Aley, P.K.; Angus, B.; Baillie, V.L.; Barnabas, S.L.; Bhorat, Q.E.; et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: A pooled analysis of four randomised trials. Lancet 2021, 397, 881–891. [Google Scholar] [CrossRef]
  8. National Institutes of Health. Janssen Investigational COVID-19 Vaccine: Interim Analysis of Phase 3 Clinical Data Released. 2021. Available online: https://www.nih.gov/news-events/news-releases/janssen-investigational-covid-19-vaccine-interim-analysis-phase-3-clinical-data-released (accessed on 16 September 2021).
  9. Logunov, D.Y.; Dolzhikova, I.V.; Shcheblyakov, D.V.; Tukhvatulin, A.I.; Zubkova, O.V.; Dzharullaeva, A.S.; Kovyrshina, A.V.; Lubenets, N.L.; Grousova, D.M.; Erokhova, A.S.; et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: An interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 2021, 397, 671–681. [Google Scholar] [CrossRef]
  10. Kim, J.H.; Marks, F.; Clemens, J.D. Looking beyond COVID-19 vaccine phase 3 trials. Nat. Med. 2021, 27, 205–211. [Google Scholar] [CrossRef]
  11. Novavax. Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial | Novavax Inc.-IR Site. 2021. Available online: https://ir.novavax.com/news-releases/news-releasedetails/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3 (accessed on 28 January 2021).
  12. Bharat Biotech. Bharat Biotech Announces Phase 3 Results of COVAXIN®: India’s First COVID-19 Vaccine Demonstrates Interim Clinical Efficacy of 81%. Available online: https://www.bharatbiotech.com/images/press/covaxinphase3-efficacy-results.pdf (accessed on 3 March 2021).
  13. Hodgson, S.H.; Mansatta, K.; Mallett, G.; Harris, V.; Emary, K.R.W.; Pollard, A.J. What defines an efficacious COVID-19 vaccine?A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. Lancet Infect. Dis. 2021, 21, e26–e35. [Google Scholar] [CrossRef]
  14. Tregoning, J.S.; Flight, K.E.; Higham, S.L.; Wang, Z.; Pierce, B.F. Progress of the COVID-19 vaccine effort: Viruses, vaccines and variants versus efficacy, effectiveness and escape. Nat. Rev. Immunol. 2021, 21, 626–636. [Google Scholar] [CrossRef]
  15. Public Health England. Public Health England Vaccine Effectiveness Report. 2021. Available online: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/989360/PHE_COVID-19_vaccine_effectiveness_report_March_2021_v2.pdf (accessed on 1 March 2021).
  16. Lopez Bernal, J.; Andrews, N.; Gower, C.; Robertson, C.; Stowe, J.; Tessier, E.; Simmons, R.; Cottrell, S.; Roberts, R.; O’Doherty, M.; et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on COVID-19 related symptoms, hospital admissions, and mortality in older adults in England: Test negative case-control study. BMJ 2021, 373, n1088. [Google Scholar] [CrossRef]
  17. Hall, V.J.; Foulkes, S.; Saei, A.; Andrews, N.; Oguti, B.; Charlett, A.; Wellington, E.; Stowe, J.; Gillson, N.; Atti, A.; et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): A prospective, multicentre, cohort study. Lancet 2021, 397, 1725–1735. [Google Scholar] [CrossRef]
  18. Mahase, E. COVID-19: Israel sees new infections plummet following vaccinations. BMJ 2021, 372, n338. [Google Scholar] [CrossRef] [PubMed]
  19. Shilo, S.; Rossman, H.; Segal, E. Signals of hope: Gauging the impact of a rapid national vaccination campaign. Nat. Rev. Immunol. 2021, 21, 198–199. [Google Scholar] [CrossRef]
  20. Bouton, T.C.; Lodi, S.; Turcinovic, J.; Schaeffer, B.; Weber, S.E.; Quinn, E.; Korn, C.; Steiner, J.; Schechter-Perkins, E.M.; Duffy, E.; et al. COVID-19 vaccine impact on rates of SARS-CoV-2 cases and post vaccination strain sequences among healthcare workers at an urban academic medical center: A prospective cohort study. Open Forum Infect Dis. 2021, 8, ofab465. [Google Scholar] [CrossRef]
  21. Thompson, M.G.; Burgess, J.L.; Naleway, A.L.; Tyner, H.L.; Yoon, S.K.; Meece, J.; Olsho, L.E.W.; Caban-Martinez, A.J.; Fowlkes, A.; Lutrick, K.; et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers—Eight U.S. locations, December 2020–March 2021. Morb. Mortal. Wkly. Rep. 2021, 70, 495. [Google Scholar]
  22. Tenforde, M.W. Effectiveness of Pfizer-BioNTech and Moderna vaccines against COVID-19 among hospitalized adults aged ≥65 years—United States, January–March 2021. MMWR Morb. Mortal. Wkly. Rep. 2021, 70, 495–500. [Google Scholar] [CrossRef]
  23. D’Arminio Monforte, A.; Tavelli, A.; De Benedittis, S.; Bai, F.; Tincati, C.; Gazzola, L.; Viganò, O.; Allegrini, M.; Mondatore, D.; Tesoro, D.; et al. Real World Estimate of Vaccination Protection in Individuals Hospitalized for COVID-19. Vaccines 2022, 10, 550. [Google Scholar] [CrossRef]
  24. Chang, S.; Liu, H.; Wu, J.; Xiao, W.; Chen, S.; Qiu, S.; Duan, G.; Song, H.; Zhang, R. Effectiveness of BNT162b2 and mRNA-1273 Vaccines against COVID-19 Infection: A Meta-Analysis of Test-Negative Design Studies. Vaccines 2022, 10, 469. [Google Scholar] [CrossRef]
  25. Sacco, C.; Mateo-Urdiales, A.; Rota, M.C.; Fabiani, M.; Boros, S.; Bressi, M.; Petrone, D.; Vescio, M.F.; Del Manso, M.; Bella, A.; et al. Infezioni da SARS-CoV-2, Ricoveri e Decessi Associati a COVID-19 Direttamente Evitati dalla Vaccinazione. Italia 27/12/2020–31/01/2022; Nota tecnica; Istituto Superiore di Sanità: Roma, Italy, 2022. [Google Scholar]
  26. Soleimanpour, S.; Yaghoubi, A. COVID-19 vaccine: Where are we now and where should we go? Expert Rev. Vaccines 2021, 20, 23–44. [Google Scholar] [CrossRef]
  27. Randolph, H.E.; Barreiro, L.B. Herd Immunity: Understanding COVID-19. Immunity 2020, 52, 737–741. [Google Scholar] [CrossRef]
  28. Murchu, O.E.; Byrne, P.; Walsh, K.A.; Carty, P.G.; Connolly, M.; De Gascun, C.; Jordan, K.; Keoghan, M.; O’Brien, K.K. Immune response following infection with SARS-CoV-2 and other coronaviruses: A rapid review. Rev. Med. Virol. 2021, 23, e2162. [Google Scholar] [CrossRef]
  29. Zhou, W.; Xu, X.; Chang, Z.; Wang, H.; Zhong, X.; Tong, X.; Liu, T.; Li, Y. The dynamic changes of serum IgM and IgG against SARSCoV-2 in patients with COVID-19. J. Med. Virol. 2021, 93, 924–933. [Google Scholar] [CrossRef]
  30. Seow, J.; Graham, C.; Merrick, B.; Acors, S.; Pickering, S.; Steel, K.J.A.; Hemmings, O.; O’Byrne, A.; Kouphou, N.; Galao, R.P.; et al. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nat. Microbiol. 2020, 5, 1598–1607. [Google Scholar] [CrossRef]
  31. Bloise, S.; Marcellino, A.; Testa, A.; Dilillo, A.; Mallardo, S.; Isoldi, S.; Martucci, V.; Sanseviero, M.T.; Del Giudice, E.; Iorfida, D.; et al. Serum IgG levels in children 6 months after SARS-CoV-2 infection and comparison with adults. Eur. J. Pediatr. 2021, 180, 3335–3342. [Google Scholar] [CrossRef]
  32. FDA Takes Key Action in Fight against COVID-19 by Issuing Emergency Use Authorization for First COVID-19 Vaccine; News Release of the Food and Drug Administration: Silver Spring, MD, USA, 11 December 2020. Available online: https://www.fda.gov/news-events/press-announcements/fda-takes-key-action-fight-against-covid-19-issuing-emergency-use-authorization-first-covid-19 (accessed on 11 December 2020).
  33. Coronavirus (COVID-19) Update: FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Adolescents in Another Important Action in Fight against Pandemic; News Release of the Food and Drug Administration: Silver Spring, MD, USA, 10 May 2021. Available online: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use (accessed on 10 May 2021).
  34. The FDA Expands Emergency Use Authorization of the Pfizer-BioNTech COVID-19 Vaccine to Include Children 5 through 11 Years of Age. Available online: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines (accessed on 29 October 2021).
  35. Comirnaty COVID-19 Vaccine: EMA Recommends Approval for Children Aged 5 to 11. Available online: https://www.ema.europa.eu/en/news/comirnaty-covid-19-vaccine-ema-recommends-approval-children-aged-5-11 (accessed on 25 November 2021).
  36. AIFA Approves Comirnaty Vaccine for Ages 5 to 11. Available online: https://www.aifa.gov.it/en/-/aifa-approva-il-vaccino-comirnaty-per-la-fascia-di-et%C3%A0-5-11-anni (accessed on 1 December 2021).
  37. Circolare Ministero della Salute 0056429-07/12/2021-DGPRE-DGPRE-P recante “Estensione di indicazione di utilizzo del vaccino Comirnatyn (BioNTech/Pfizer) per la fascia di età 5–11 anni”. Available online: https://www.ordinemedicifc.it/2021/12/10/circolare-ministero-della-salute-0056429-07-12-2021-dgpre-dgpre-p-recante-estensione-di-indicazione-di-utilizzo-del-vaccino-comirnatyn-biontech-pfizer-per-la-fascia-di-eta-5-11-anni/ (accessed on 10 December 2021).
  38. Lubrano, R.; Bloise, S.; Testa, A.; Marcellino, A.; Dilillo, A.; Mallardo, S.; Isoldi, S.; Martucci, V.; Sanseviero, M.; Del Giudice, E.; et al. Assessment of Respiratory Function in Infants and Young Children Wearing Face Masks during the COVID-19 Pandemic. JAMA Netw. Open. 2021, 4, e210414. [Google Scholar] [CrossRef]
  39. Lubrano, R.; Bloise, S.; Marcellino, A.; Ciolli, C.P.; Testa, A.; De Luca, E.; Dilillo, A.; Mallardo, S.; Isoldi, S.; Martucci, V.; et al. Effects of N95 Mask Use on Pulmonary Function in Children. J. Pediatr. 2021, 237, 143–147. [Google Scholar] [CrossRef]
  40. Lubrano, R.; Bloise, S.; Marcellino, A.; Proietti Ciolli, C.; Testa, A.; De Luca, E.; Dilillo, A.; Mallardo, S.; Isoldi, S.; Martucci, V.; et al. Assessment of respiratory function in children wearing a N95 mask with or without an exhalation valve: Data compared. Data Brief. 2021, 39, 107550. [Google Scholar] [CrossRef]
  41. Lubrano, R.; Del Giudice, E.; Marcellino, A.; Ventriglia, F.; Dilillo, A.; De Luca, E.; Mallardo, S.; Isoldi, S.; Martucci, V.; Sanseviero, M.; et al. Change in Pediatric Health Care Spending and Drug Utilization during the COVID-19 Pandemic. Children 2021, 8, 1183. [Google Scholar] [CrossRef]
  42. Eberhardt, C.S.; Siegrist, C.A. Is there a role for childhood vaccination against COVID-19? Pediatr. Allergy Immunol. 2021, 32, 9–16. [Google Scholar] [CrossRef]
  43. Circolare del Ministero della Salute-Vaccinazione dei Soggetti che Hanno avuto un’infezione da SARS-CoV-2. Available online: https://www.salute.gov.it/portale/p5_1_2.jsp?lingua=italiano&id=255 (accessed on 22 July 2021).
  44. Walter, E.B.; Talaat, K.R.; Sabharwal, C.; Gurtman, A.; Lockhart, S.; Paulsen, G.C.; Barnett, E.D.; Muñoz, F.M.; Maldonado, Y.; Pahud, B.A.; et al. Evaluation of the BNT162b2 COVID-19 Vaccine in Children 5 to 11 Years of Age. N. Engl. J. Med. 2022, 386, 35–46. [Google Scholar] [CrossRef]
  45. Creech, C.B.; Anderson, E.; Berthaud, V.; Yildirim, I.; Atz, A.M.; Melendez Baez, I.; Finkelstein, D.; Pickrell, P.; Kirstein, J.; Yut, C.; et al. KidCOVE Study Group. Evaluation of mRNA-1273 Covid19 Vaccine in Children 6 to 11 Years of Age. N. Engl. J. Med. 2022, 386, 2011–2023. [Google Scholar] [CrossRef]
  46. Hause, A.M.; Baggs, J.; Marquez, P.; Myers, T.R.; Gee, J.; Su, J.R.; Zhang, B.; Thompson, D.; Shimabukuro, T.T.; Shay, D.K. COVID-19 Vaccine Safety in Children Aged 5–11 Years-United States, November 3-December 19, 2021. MMWR Morb. Mortal Wkly. Rep. 2021, 70, 1755–1760. [Google Scholar] [CrossRef] [PubMed]
  47. Zheng, Y.J.; Wang, X.C.; Feng, L.Z.; Xie, Z.D.; Jiang, Y.; Lu, G.; Li, X.W.; Jiang, R.M.; Deng, J.K.; Liu, M.; et al. Expert consensus on COVID-19 vaccination in children. World J. Pediatr. 2021, 17, 449–457. [Google Scholar] [CrossRef] [PubMed]
  48. Xu, W.; Tang, J.; Chen, C.; Wang, C.; Wen, W.; Cheng, Y.; Zhou, M.; Wu, Q.; Zhang, X.; Feng, Z.; et al. Safety and efficacy of the COVID-19 vaccine in children and/or adolescents: A meta-analysis. J. Infect. 2022, 84, 722–746. [Google Scholar] [CrossRef] [PubMed]
  49. Hause, A.M.; Shay, D.K.; Klein, N.P.; Abara, W.E.; Baggs, J.; Cortese, M.M.; Fireman, B.; Gee, J.; Glanz, J.M.; Goddard, K.; et al. Safety of COVID-19 Vaccination in US Children Ages 5–11 Years. Pediatrics 2022, 150, e2022057313. [Google Scholar] [CrossRef] [PubMed]
  50. Oster, M.E.; Shay, D.K.; Su, J.R.; Gee, J.; Creech, C.B.; Broder, K.R.; Edwards, K.; Soslow, J.H.; Dendy, J.M.; Schlaudecker, E.; et al. Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. JAMA 2022, 327, 331–340. [Google Scholar] [CrossRef]
  51. Oliver, S.E.; Wallace, M.; Link-Gelles, R. COVID-19 Vaccines: Safe and Effective in Children Ages 5–11 Years. Pediatrics 2022, 150, e2022057314. [Google Scholar] [CrossRef]
  52. Nygaard, U.; Holm, M.; Dungu, K.H.S.; Matthesen, A.T.; Stensballe, L.G.; Espenhain, L.; Hartling, U. Risk of Myopericarditis After COVID-19 Vaccination in Danish Children Aged 5–11 Years. Pediatrics 2022, 150, e2022057508. [Google Scholar] [CrossRef]
  53. Miraglia Del Giudice, G.; Napoli, A.; Corea, F.; Folcarelli, L.; Angelillo, I.F. Evaluating COVID-19 Vaccine Willingness and Hesitancy among Parents of Children Aged 5–11 Years with Chronic Conditions in Italy. Vaccines 2022, 10, 396. [Google Scholar] [CrossRef]
  54. Novembre, E.; Tosca, M.; Caffarelli, C.; Calvani, M.; Cardinale, F.; Castagnoli, R.; Chiappini, E.; Cravidi, C.; Del Giudice, M.M.; Duse, M.; et al. Management of BNT162b2 mRNA COVID-19 vaccine in children aged 5–11 years with allergies, asthma, and immunodeficiency: Consensus of the Italian Society of Pediatric Allergy and Immunology (SIAIP). Ital. J. Pediatr. 2022, 48, 76. [Google Scholar] [CrossRef]
  55. Tsankov, B.K.; Allaire, J.M.; Irvine, M.A.; Lopez, A.A.; Sauvé, L.J.; Vallance, B.A.; Jacobson, K. Severe COVID-19 Infection and Pediatric Comorbidities: A Systematic Review and Meta-Analysis. Int. J. Infect. Dis. 2021, 103, 246–256. [Google Scholar] [CrossRef]
  56. Ejaz, H.; Alsrhani, A.; Zafar, A.; Javed, H.; Junaid, K.; Abdalla, A.E.; Abosalif, K.O.A.; Ahmed, Z.; Younas, S. COVID-19 and comorbidities: Deleterious impact on infected patients. J. Infect. Public Health 2020, 13, 1833–1839. [Google Scholar] [CrossRef]
  57. Sacco, C.; Del Manso, M.; Mateo-Urdiales, A.; Rota, M.C.; Petrone, D.; Riccardo, F.; Bella, A.; Siddu, A.; Battilomo, S.; Proietti, V.; et al. Effectiveness of BNT162b2 vaccine against SARS-CoV-2 infection and severe COVID-19 in children aged 5–11 years in Italy: A retrospective analysis of January–April, 2022. Lancet 2022, 400, 97–103. [Google Scholar] [CrossRef]
  58. Dorabawila, V.; Hoefer, D.; Bauer, U.E.; Bassett, M.T.; Lutterloh, E.; Rosenberg, E.S. Effectiveness of the BNT162b2 vaccine among children 5–11 and 12–17 years in New York after the emergence of the omicron variant. JAMA 2022, 327, 2242–2244. [Google Scholar] [CrossRef]
  59. Chen, L.L.; Chua, G.T.; Lu, L.; Chan, B.P.; Wong, J.S.; Chow, C.C.; Yu, T.C.; Leung, A.S.; Lam, S.Y.; Wong, T.W.; et al. Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine. Emerg Microbes Infect. 2022. Emerg. Microbes Infect. 2022, 11, 543–547. [Google Scholar] [CrossRef]
  60. Lauring, A.S.; Tenforde, M.W.; Chappell, J.D.; Gaglani, M.; Ginde, A.A.; McNeal, T.; Ghamande, S.; Douin, D.J.; Talbot, H.K.; Casey, J.D.; et al. Clinical severity of, and effectiveness of mRNA vaccines against, COVID-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: Prospective observational study. BMJ 2022, 376, e069761. [Google Scholar] [CrossRef]
  61. Price, A.M.; Olson, S.M.; Newhams, M.M.; Halasa, N.B.; Boom, J.A.; Sahni, L.C.; Pannaraj, P.S.; Irby, K.; Bline, K.E.; Maddux, A.B.; et al. BNT162b2 Protection against the Omicron Variant in Children and Adolescents. N. Engl. J. Med. 2022, 386, 1899–1909. [Google Scholar] [CrossRef]
  62. Klein, N.P.; Stockwell, M.S.; Demarco, M.; Gaglani, M.; Kharbanda, A.B.; Irving, S.A.; Rao, S.; Grannis, S.J.; Dascomb, K.; Murthy, K.; et al. Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5–17 Years-VISION Network, 10 States, April 2021-January 2022. MMWR Morb. Mortal Wkly. Rep. 2022, 71, 352–358. [Google Scholar] [CrossRef] [PubMed]
  63. Expósito Singh, D.; Olmedo Lucerón, C.; Limia Sánchez, A.; Guzmán Merino, M.; Carretero, J. Impact of vaccination against COVID-19 in children aged 5–11 years: A mathematical model. Rev. Esp. Salud. Publica 2022, 96, e202202021. [Google Scholar]
  64. Park, Y.J.; Choe, Y.J.; Park, O.; Park, S.Y.; Kim, Y.M.; Kim, J.; Kweon, S.; Woo, Y.; Gwack, J.; Kim, S.S.; et al. Contact Tracing during Coronavirus Disease Outbreak, South Korea, 2020. Emerg. Infect. Dis. 2020, 26, 2465–2468. [Google Scholar] [CrossRef]
  65. Paul, L.A.; Daneman, N.; Schwartz, K.L.; Science, M.; Brown, K.A.; Whelan, M.; Chan, E.; Buchan, S.A. Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection. JAMA Pediatr. 2021, 175, 1151–1158. [Google Scholar] [CrossRef]
  66. Chu, V.T.; Yousaf, A.R.; Chang, K.; Schwartz, N.G.; McDaniel, C.J.; Lee, S.H.; Szablewski, C.M.; Brown, M.; Drenzek, C.L.; Dirlikov, E.; et al. Household Transmission of SARS-CoV-2 from Children and Adolescents. N. Engl. J. Med. 2021, 385, 954–956. [Google Scholar] [CrossRef]
  67. Castagnoli, R.; Votto, M.; Licari, A.; Brambilla, I.; Bruno, R.; Perlini, S.; Rovida, F.; Baldanti, F.; Marseglia, G.L. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. JAMA Pediatr. 2020, 174, 882–889. [Google Scholar] [CrossRef][Green Version]
  68. Isoldi, S.; Mallardo, S.; Marcellino, A.; Bloise, S.; Dilillo, A.; Iorfida, D.; Testa, A.; Del Giudice, E.; Martucci, V.; Sanseviero, M.; et al. The comprehensive clinic, laboratory, and instrumental evaluation of children with COVID-19: A 6-months prospective study. J. Med. Virol. 2021, 93, 3122–3132. [Google Scholar] [CrossRef]
  69. Zimmermann, P.; Pittet, L.F.; Curtis, N. How Common is Long COVID in Children and Adolescents? Pediatr. Infect. Dis. J. 2021, 40, e482–e487. [Google Scholar] [CrossRef]
  70. Nakra, N.A.; Blumberg, D.A.; Herrera-Guerra, A.; Lakshminrusimha, S. Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. Children 2020, 7, 69. [Google Scholar] [CrossRef]
  71. Bloise, S.; Isoldi, S.; Marcellino, A.; De Luca, E.; Dilillo, A.; Mallardo, S.; Martucci, V.; Sanseviero, M.; Del Giudice, E.; Iorfida, D.; et al. Clinical picture and long-term symptoms of SARS-CoV-2 infection in an Italian pediatric population. Ital. J. Pediatr. 2022, 48, 79. [Google Scholar] [CrossRef]
  72. Antonelli, M.; Penfold, R.S.; Merino, J.; Sudre, C.H.; Molteni, E.; Berry, S.; Canas, L.S.; Graham, M.S.; Klaser, K.; Modat, M.; et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: A prospective, community-based, nested, case-control study. Lancet Infect. Dis. 2021, 22, 43–55. [Google Scholar] [CrossRef]
  73. Wallace, M. COVID-19 mRNA vaccines in adolescents and young adults: Benefit risk discussion 2021. In Proceedings of the ACIP Meeting, Online, 23 June 2021. [Google Scholar]
  74. CDC Encourages Vaccination of Children to Prevent MIS-C, a Rare Illness Linked to Coronavirus|Health News|US News. Available online: https://www.usnews.com/news/health-news/articles/2021-06-17/cdc-encourages-vaccination-of-childrento-prevent-mis-c-a-rare-illness-linked-to-coronavirus (accessed on 1 November 2021).
  75. Ashikkali, L.; Carroll, W.; Johnson, C. The indirect impact of COVID-19 on child health. Paediatr. Child Health 2020, 30, 430–437. [Google Scholar] [CrossRef]
  76. Sivertsen, B.; Knapstad, M.; Petrie, K.; O’Connor, R.; Lønning, K.J.; Hysing, M. Changes in mental health problems and suicidal behaviour in students and their associations with COVID-19-related restrictions in Norway: A national repeated cross-sectional analysis. BMJ Open 2022, 12, e057492. [Google Scholar] [CrossRef]
  77. Ye, J. Pediatric Mental and Behavioral Health in the Period of Quarantine and Social Distancing With COVID-19. JMIR Pediatr. Parent. 2020, 3, e19867. [Google Scholar] [CrossRef]
  78. Stein, M.; Ashkenazi-Hoffnung, L.; Greenberg, D.; Dalal, I.; Livni, G.; Chapnick, G.; Stein-Zamir, C.; Ashkenazi, S.; Hecht-Sagie, L.; Grossman, Z. The Burden of COVID-19 in Children and Its Prevention by Vaccination: A Joint Statement of the Israeli Pediatric Association and the Israeli Society for Pediatric Infectious Diseases. Vaccines 2022, 10, 81. [Google Scholar] [CrossRef]
Vaccines 10 01224 g001 550
Figure 1. Adverse Events 24–48 h after first dose.
Figure 1. Adverse Events 24–48 h after first dose.
Vaccines 10 01224 g001
Vaccines 10 01224 g002 550
Figure 2. Flowchart patients enrolled.
Figure 2. Flowchart patients enrolled.
Vaccines 10 01224 g002
Vaccines 10 01224 g003 550
Figure 3. Adverse events 24–48 h after second dose.
Figure 3. Adverse events 24–48 h after second dose.
Vaccines 10 01224 g003
Table
Table 1. Children’s clinical and demographic characteristics.
Table 1. Children’s clinical and demographic characteristics.
Children’s Characteristics
Sex (F/M), % (n)55.9 (318)/44.1 (251)
Age (median ± DS), months114 ± 4.24
Comorbidities % (n)None:
Comorbidity80.7 (459)
Allergies19.3 (110)
Asthma46 (51)
Gastrointestinal diseases24 (26)
Cardiac disease9 (10)
Neurological diseases8 (9)
Nephrological diseases7 (8)
Rheumatological diseases3 (3)
Other diseases1 (1)
Previous
SARS-CoV-2 infection % (n)		6.4 (37)
Clinical course of the infectionAsymptomatic41.7 (15)
Symptomatic58.3 (22)
Fever71.4 (16)
Respiratory symptoms42.8 (9)
Headache33.4 (7)
Gastrointestinal symptoms14.2 (3)
Asthenia9.5 (2)
Arthralgias4.8 (1)
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Bloise, S.; Marcellino, A.; Frasacco, B.; Gizzone, P.; Proietti Ciolli, C.; Martucci, V.; Sanseviero, M.; Del Giudice, E.; Ventriglia, F.; Lubrano, R. Cross-Sectional Survey on BNT162b2 mRNA COVID-19 Vaccine Serious Adverse Events in Children 5 to 11 Years of Age: A Monocentric Experience. Vaccines 2022, 10, 1224. https://doi.org/10.3390/vaccines10081224

AMA Style

Bloise S, Marcellino A, Frasacco B, Gizzone P, Proietti Ciolli C, Martucci V, Sanseviero M, Del Giudice E, Ventriglia F, Lubrano R. Cross-Sectional Survey on BNT162b2 mRNA COVID-19 Vaccine Serious Adverse Events in Children 5 to 11 Years of Age: A Monocentric Experience. Vaccines. 2022; 10(8):1224. https://doi.org/10.3390/vaccines10081224

Chicago/Turabian Style

Bloise, Silvia, Alessia Marcellino, Beatrice Frasacco, Pietro Gizzone, Claudia Proietti Ciolli, Vanessa Martucci, Mariateresa Sanseviero, Emanuela Del Giudice, Flavia Ventriglia, and Riccardo Lubrano. 2022. "Cross-Sectional Survey on BNT162b2 mRNA COVID-19 Vaccine Serious Adverse Events in Children 5 to 11 Years of Age: A Monocentric Experience" Vaccines 10, no. 8: 1224. https://doi.org/10.3390/vaccines10081224

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop