BACKGROUND AND OBJECTIVES

On June 4, 2021, Italy launched the coronavirus disease 2019 (COVID-19) vaccination of adolescents to slow down the COVID-19 spread. Although clinical trials have evaluated messenger ribonucleic acid (mRNA) vaccine effectiveness in adolescents, there is limited literature on its real-world effectiveness. Accordingly, this study aimed to estimate the effectiveness of mRNA COVID-19 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild or severe COVID-19 in a cohort of Sicilian adolescents within a 6 month observation period.

METHODS

A retrospective cohort study was conducted with adolescents aged 12 to 18 years, residents of Sicily, who were followed from July 15 to December 31, 2021. SARS-CoV-2 infections, mild and severe COVID-19, and COVID-19-related intubation or deaths during the study period were compared between subjects vaccinated with 2 doses of mRNA vaccines and unvaccinated individuals. The Cox regression analysis, adjusted for age and sex, was performed to compare the 2 groups.

RESULTS

Overall, the study included a total at-risk population of 274 782 adolescents with 61.4% of them having completed the vaccination cycle by the end of the study. Unvaccinated subjects had higher incidence rates of SARS-CoV-2 (1043 × 10 000 vs 158.7 × 10 000 subjects), mild COVID-19 (27.7 × 10 000 vs 1.8 × 10 000 subjects) and severe COVID-19 (1.41 × 10 000 vs 0 subjects) compared with the vaccinated population. The estimated adjusted vaccine effectiveness against SARS-CoV-2 infection was 71.2%, reaching 92.1% and 97.9% against mild and severe COVID-19, respectively.

CONCLUSIONS

This study provides rigorous evidence of mRNA COVID-19 vaccines’ effectiveness in protecting adolescents from both SARS-CoV-2 infection and COVID-19.

What’s Known on this Subject:

Clinical trials have already evaluated the vaccine effectiveness of mRNA vaccination in adolescents. In this population group, apparently at a lower risk of COVID-19-related severe outcomes and death, some studies revealed COVID-19 long-term effects and many cases of hospitalizations.

What This Study Adds:

Rigorous evidence of primary mRNA COVID-19 vaccine effectiveness in protecting adolescents from both severe acute respiratory syndrome coronavirus 2 infection and mild-to-severe COVID-19 in a real-world setting. Findings should be considered when discussing health policies toward children, given consistent dataset size and analyzed time interval.

Coronavirus disease 2019 (COVID-19) has caused >545 000 000 infections and >6 330 000 deaths worldwide as of July 5, 2022.1  The typical symptoms of COVID-19 include asthenia, fever, chills, cough, shortness of breath, sore throat, diarrhea, muscle or body aches, dysgeusia or dysosmia, loss of appetite, and respiratory symptoms.2 

Elderly people are more susceptible to severe disease, which in most cases may require hospitalization or intubation, and, eventually, death from COVID-19.36  Although children and adolescents appear to have a lower risk of severe COVID-19-related outcomes and death, some studies have revealed long-term effects and hospitalization, with up to one-third of the patients subsequently being admitted to the ICU,7  especially in the presence of comorbidities.8  Moreover, adolescents may develop complications like the multisystem inflammatory syndrome in children, a Kawasaki-like disease presenting with rash, gastrointestinal symptoms, fever, and myocarditis that can lead to myocardial failure.9,10 

European countries and the United States have reached high vaccination rates among adults, with overall vaccination rates of 83.4% and 76,8% as of June 30, 2022, respectively.11,12  To reach herd immunity, messenger ribonucleic acid (mRNA) vaccine indications were extended to adolescents given their favorable safety profile and risk-to-benefit ratio.13,14  COVID-19 vaccination among adolescents was introduced in Italy on June 4, 2021 thanks to the Italian Medicines Agency’s extension approval of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine on May 31, 2021. A few weeks later, 3 days after its extension was approved, on July 26, the mRNA-1273 vaccine (Spikevax, Moderna vaccine) also started to be administered to the adolescents.15,16  By September 8, 2021, 47.6% of Italian adolescents had received the primary COVID-19 vaccination series, reaching a percentage of 74.2% by January 5, 2022.17,18 

Although clinical trials have evaluated the efficacy of mRNA vaccines in adolescents, there is limited literature on their real-world effectiveness, and the international medical community strongly recommends the improvement of the current knowledge on this topic. Therefore, the current study aimed to estimate the effectiveness of mRNA COVID-19 vaccines (vaccine effectiveness; VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild or severe COVID-19 in a cohort of Sicilian adolescents observed between July 15, 2021 and December 31, 2021.

This is a retrospective cohort study on Sicilian adolescents aged 12 to 18 years who received 2 doses of an mRNA COVID-19 vaccine compared with unvaccinated adolescents. The cohort was observed from July 15, 2021 to December 31, 2021. All demographic data were obtained from the Italian National Statistics Institute. Two electronic health registries collected by the Sicilian Regional Health Office under the supervision of the Italian Ministry of Health were used to gather information about the dates of the first and the second vaccine doses, as well as the specific vaccine brand and SARS-CoV-2 infections in adolescents. Diagnosis of SARS-CoV-2 infection was based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs specimens. Nasopharyngeal swabs have been collected in medical, domestic, and school settings, not only by hospital-based physicians and nurses but also by the special continuity of care units that are small teams of health care workers who follow suspected and confirmed SARS-CoV-2 patients over weeks.19  Moreover, for each SARS-CoV-2-positive patient, the database provides clinical information (ie, the date of the first positive test result, the occurrence and date of symptoms, hospitalization, admission to ICU, intubation, and death) if present.

The databases were merged by using the Italian identification code as a key to connect the relevant information to a single participant. This key is an alphanumeric code of 16 characters that unambiguously identifies individuals, independently of citizenship or residency status.

The final database included the 2 groups of vaccinated and unvaccinated individuals, and the time of each of the following distinct events was documented: SARS-CoV-2 positivity, mild COVID-19, severe COVID-19, intubation, and death.

All subjects meeting the following criteria were excluded from the study:

  • Administration of a viral-vector COVID-19 vaccine.

  • SARS-CoV-2-positive RT-PCR test result before the beginning of the study.

  • Administration of the second dose of COVID-19 vaccine before July 8, 2021. This criterium was applied to avoid the inclusion of a small group of frail vaccinated adolescents (individuals with comorbidities) who would have led to an underestimation of VE in the final observation period.

According to the previous criteria, a total of 274 782 Sicilian adolescents entered the study cohort.

SARS-CoV-2-positive subjects were considered cases regardless of the presence of signs and/or symptoms. These cases were categorized as mild or severe COVID-19 cases according to the Italian National Classification Criteria. Mild COVID-19 entails any clinical manifestation of the respiratory tract or other organ systems that did not require hospital treatment; conversely, severe COVID-19 entails clinical manifestations of the respiratory tract or other organs that required hospitalization or admission to the ICU.

To evaluate VE against SARS-CoV-2 infection, we considered the person-time exposure of each participant by dividing the study population into 4 categories according to vaccination status (ie, vaccinated vs unvaccinated) and the presence of SARS-CoV-2 infection (ie, infected vs uninfected):

  • Vaccine −/COVID-19 −: Unvaccinated and uninfected subjects during the observation period. Adolescents who received only 1 dose of an mRNA COVID-19 vaccine were considered unvaccinated and uninfected as long as there were no positive RT-PCR test results.

  • Vaccine +/COVID-19 +: Vaccinated and infected subjects. This group included adolescents who received 2 doses of an mRNA COVID-19 vaccine before being infected by SARS-CoV-2. The follow-up period for this group started 7 days after the administration of the second dose (at least 28 days after the first vaccine dose) and ended at the date of detection of SARS-CoV-2 infection.

  • Vaccine −/COVID-19 +: Unvaccinated and infected subjects. This group was observed from the beginning of the study up to the date of SARS-CoV-2 infection.

  • Vaccine +/COVID-19 −: Fully vaccinated (2 doses of an mRNA vaccine) and uninfected subjects during the observation period. Their observation started 7 days after the date of the second dose of the COVID-19 vaccination until the of the study.

The qualitative data were summarized by absolute and relative frequency (%), whereas the quantitative data are presented as mean ± standard deviation if normally distributed and median and interquartile range if not normally distributed. The Kolmogorov-Smirnov test was used to evaluate the normality of the distribution of the quantitative data. The overall cumulative incidence rates were assessed by using the Kaplan-Meier method, and the vaccinated and unvaccinated groups were compared by using the log-rank test.

Hazard ratios (HR) and 95% confidence intervals (CI) were calculated with the Cox regression test by comparing the rates of SARS-CoV-2 infection, and mild or severe COVID-19 cases of vaccinated and unvaccinated subjects. The multivariable Cox regression analysis was conducted, including age and sex as potential confounders. VE was calculated as 1 - HR × 100. All the analyses were performed on R statistical software (version 4.0.5) using the statistical packages “metafor,” “survival,” “epiDisplay,” “ggplot2,” and “ggfortify.” All P values <.05 were considered statistically significant.20 

As reported in Table 1, 274 782 Sicilian adolescents aged 12 to 18 years (males-to-females ratio: 1.06) were observed from July 15, 2021 to December 31, 2021. During the study period, 168 633 (61.4%) subjects received 2 doses of an mRNA COVID-19 vaccine. The majority of the subjects (122 919; 72.9%) completed the vaccination between August and October.

TABLE 1

Characteristics of the Cohort of 274 782 Sicilian Adolescents Aged 12 to 18 Years Who Were Tracked From July 15, 2021 to December 31, 2021

TotalVaccinatedUnvaccinated
N (%) 274 782 (100) 168 633 (61.4) 106 149 (38.6) 
Sex, n (%)a    
 Male 141 683 (51.6) 86 482 (51.3) 55 201 (52) 
 Female 133 091 (48.4) 82 146 (48.7) 50 945 (48) 
Clinical status, n (×10 000 subjects)    
 SARS-CoV-2 infected 13 747 (500.3) 2676 (158.7) 11 071 (1043) 
 Mild COVID-19 325 (11.8) 31 (1.84) 294 (27.7) 
 Severe COVID-19 15 (0.54) 0 (0) 15 (1.41) 
Clinical status, n (×10 000 SARS-CoV-2-positive subjects)    
 Mild COVID-19 325 (236.4) 31 (115.8) 294 (265.6) 
 Severe COVID-19 15 (10.9) 0 (0) 15 (13.5) 
TotalVaccinatedUnvaccinated
N (%) 274 782 (100) 168 633 (61.4) 106 149 (38.6) 
Sex, n (%)a    
 Male 141 683 (51.6) 86 482 (51.3) 55 201 (52) 
 Female 133 091 (48.4) 82 146 (48.7) 50 945 (48) 
Clinical status, n (×10 000 subjects)    
 SARS-CoV-2 infected 13 747 (500.3) 2676 (158.7) 11 071 (1043) 
 Mild COVID-19 325 (11.8) 31 (1.84) 294 (27.7) 
 Severe COVID-19 15 (0.54) 0 (0) 15 (1.41) 
Clinical status, n (×10 000 SARS-CoV-2-positive subjects)    
 Mild COVID-19 325 (236.4) 31 (115.8) 294 (265.6) 
 Severe COVID-19 15 (10.9) 0 (0) 15 (13.5) 
a

Data were missing for 10 subjects.

Unvaccinated subjects had higher incidence rates of SARS-CoV-2 (1043 × 10 000 vs 158.7 × 10 000 subjects), mild COVID-19 (27.7 × 10 000 vs 1.8 × 10 000 subjects), and severe COVID-19 (1.41 × 10 000 vs 0 subjects) compared with the vaccinated counterpart.

During the follow-up period, a total of 13 747 (500.3 × 10 000 of the entire cohort) SARS-CoV-2 positive cases were observed, with the first peak of incidence occurring in August and the second peak (higher than the first one) in December (Fig 1). In Table 2, 3 different multivariable Cox regression analysis models are presented corresponding to SARS-CoV-2 infection, mild COVID-19, and severe COVID-19. In all the models, vaccination was significantly protective against both SARS-CoV-2 infection (adj-HR: 0.29; 95% CI: 0.28–0.30), mild COVID-19 (adj-HR: 0.08; 95% CI: 0.05–0.12), and severe COVID-19 (adj-HR: 0.021; 95% CI: 0.0003–0.074).

FIGURE 1

Epidemic curve of SARS-CoV-2 cases observed among Sicilian adolescents between July 15, 2021 and December 31, 2021.

FIGURE 1

Epidemic curve of SARS-CoV-2 cases observed among Sicilian adolescents between July 15, 2021 and December 31, 2021.

Close modal
TABLE 2

Multivariable Analyses of Vaccinated in Comparison With Unvaccinated Children

HR95% CIP
Model 1: against infection    
 Vaccine (ref. no) 0.29 0.28–0.30 <.001 
 Sex (ref. female) 0.93 0.89–0.96 <.001 
 Age in y, per unit increment 1.07 1.06–1.08 <.001 
Model 2: against mild disease    
 Vaccine (ref. no) 0.08 0.05–0.12 <.001 
 Sex (ref. female) 1.05 0.85–1.31 .65 
 Age in y, per unit increment 1.17 1.10–1.24 <.001 
Model 3: against severe disease    
 Vaccine (ref. no) 0.021 0.0003–0.074 .0014 
 Sex (ref. female) 1.43 0.51–4.01 .50 
 Age in y, per unit increment 1.41 1.04–1.92 .02 
HR95% CIP
Model 1: against infection    
 Vaccine (ref. no) 0.29 0.28–0.30 <.001 
 Sex (ref. female) 0.93 0.89–0.96 <.001 
 Age in y, per unit increment 1.07 1.06–1.08 <.001 
Model 2: against mild disease    
 Vaccine (ref. no) 0.08 0.05–0.12 <.001 
 Sex (ref. female) 1.05 0.85–1.31 .65 
 Age in y, per unit increment 1.17 1.10–1.24 <.001 
Model 3: against severe disease    
 Vaccine (ref. no) 0.021 0.0003–0.074 .0014 
 Sex (ref. female) 1.43 0.51–4.01 .50 
 Age in y, per unit increment 1.41 1.04–1.92 .02 

Moreover, older individuals were significantly more likely to develop SARS-CoV-2 infection and mild or severe COVID-19. In Model 1, males were significantly less susceptible to SARS-CoV-2 infection. However, sex was not statistically significant in Models 2 and 3.

The Kaplan-Meier survival analyses revealed that the incidence rates of SARS-CoV-2 infection, mild COVID-19, and severe COVID-19 in unvaccinated subjects were significantly higher than those in vaccinated subjects (log-rank test; P < .001 for all 3 groups; Fig 2).

FIGURE 2

Time to (A) SARS-CoV-2 infection, (B) mild COVID-19, and (C) severe COVID-19.

FIGURE 2

Time to (A) SARS-CoV-2 infection, (B) mild COVID-19, and (C) severe COVID-19.

Close modal

Figure 3 summarizes the estimated VE after adjustment for age and sex according to the different outcomes and observation periods. The adjusted VE was 71.2% against SARS-CoV-2 infection, 92.1% against mild COVID-19, and 97.9% against severe COVID-19.

FIGURE 3

Adjusted VE against SARS-CoV-2 infection, mild COVID-19, and severe disease.

FIGURE 3

Adjusted VE against SARS-CoV-2 infection, mild COVID-19, and severe disease.

Close modal

The effectiveness of mRNA COVID-19 vaccines in adolescents requires careful assessment because some studies reveal that the incidence rate of SARS-CoV-2 infection among adolescents is similar to that of adults and, thus, it is important to evaluate vaccines performances, level of protection against different SARS-CoV-2 variants, duration of vaccine-induced immunity, and their contribution to herd immunity.2123 

The results presented in this study confirm that mRNA vaccines prevent SARS-CoV-2 infection and spread, as already highlighted in the current literature.2426  In our study, the adjusted VE of a complete vaccination cycle against infection was 71.3%, reaching 92.1% and 97.9% in the case of mild and severe COVID-19, respectively. These results coincide with a recent report featuring a large followed-up cohort and real-world data.27  A multinational clinical trial conducted by Frenck et al13  documented VE of 100% (95% CI; 75.3%–100%) among 2260 subjects aged 12 to 15 years. Regarding severe COVID-19 outcomes in adolescents, Olson et al28  found that VE against COVID-19-induced hospitalization was 93% (95% CI; 83%–97%). Price et al29  assessed that the risk of omicron-associated hospitalization was reduced by two-thirds (95% CI; 42%–82%) among children aged 5 to 11 years after BNT162b2 vaccination, whereas the risk of severe COVID-19 was reduced by roughly 79% (95% CI; 51%–91%) in the 12 to 18 age group. These findings support the thesis that a complete vaccination cycle reduces the overall risk of infection and severe disease, encouraging the policymakers’ vaccination campaigns.12,18,30,31 

Another important finding of this study is the role of age in determining an increased risk for both SARS-CoV-2 infection and mild or severe COVID-19. It has been shown that the older the adolescents, the more they are at risk for developing asymptomatic and symptomatic SARS-CoV-2 infection. This could be explained by social behavior patterns in the population of 15 to 18 year olds that may determine a higher transmission rate, as partially confirmed by Tartof et al’s study,32  in which the 12 to 15 age group presented higher VE than the 16 to 44 age group (91%; 95% CI: 88%–93% vs 73%; 95% CI: 72%–74%, respectively).

One of the strengths of the current study is the estimation of medium-term VE. We observed a progressive decline in VE over time, with most of the infections detected 100 days after the primary vaccination course. This is in line with a study on adolescent residents of Israel, where VE against asymptomatic and symptomatic infection was 75% to 78% within 3 to 5 months after vaccination, although it decreased to 58% against SARS-CoV-2 infection and 65% against COVID-19 disease after 5 months.33,34 

Overall, the authors of this study conducted one of the most important investigations on COVID-19 vaccine effectiveness among adolescents; nevertheless, it has some limitations. First, it was impossible to quantify VE against SARS-CoV-2 variants, although it is epidemiologically plausible that the collected data mostly corresponded to VE against the delta strain and, starting in November 2021, against the omicron variant, too. Second, no comorbidities, lifestyle risk factors, or general at-risk behaviors were accounted for. Consequently, the cohort was not stratified according to preexisting diseases, immunodeficiency disorders, immunosuppressive therapies, and tobacco or alcohol consumption. In addition, it was not possible to document the time of exposure to the recommendations for the prevention of COVID-19 (eg, hand hygiene practices, wearing and regularly changing masks).

In line with the scope of the study and the observation period, all collected data excluded adolescents who had received the second dose of the vaccine before July 7, 2021. This choice was aimed at excluding vulnerable adolescents from the cohort because they had priority access to vaccination. Moreover, data regarding ethnicity were not available; thus, it was not possible to investigate possible differences in terms of the general response to the infection according to specific ethnic groups. Another limitation was the reliability of the symptoms’ severity, whose documentation depended on the operators’ discretion and the patients’ self-declaration, leading to a potential misclassification that is not quantifiable.

Finally, it is worth mentioning that this study did not consider vaccine safety outcomes. In fact, although mRNA vaccines were shown to have an acceptable safety profile,13,35  recently, mRNA-1273 vaccine-related myocarditis occurrence, although rare, has been documented specifically among males aged 18 to 39, with the highest risk in the age range of 18 to 24.36  Additional studies are necessary to investigate on this topic.

This study provides rigorous evidence of mRNA COVID-19 vaccine effectiveness in protecting adolescents from both SARS-CoV-2 infection and mild or severe COVID-19. Our findings should be considered when discussing health policies directed toward younger age groups, given the consistent sample size and the analyzed period (up to 180 days after vaccination). In addition, the general adjusted VE of 71.3% is considered effective despite its progressive decrease over time. Considering the favorable safety profile, this study reinforces the importance of vaccination of adolescents, underlying its role in the perspective of public health.

Dr Amodio contributed to the development of study methods, developed the statistical analysis plan, performed the descriptive analysis, interpreted the results, drafted the initial manuscript, and reviewed and revised the manuscript; Drs Genovese and Calamusa conceptualized and designed the study, contributed to the development of study methods, contributed to the interpretation of the results, and critically reviewed the manuscript for important intellectual content; Drs Mazzeo and Vella contributed to the data analysis and interpretation of the results, and critically reviewed the manuscript for important intellectual content; Drs Martino and Restivo were responsible for data linkage and standardization, critically reviewed the manuscript for important intellectual content and reviewed and revised the manuscript; Dr Vitale conceptualized and designed the study, supervised the work, contributed to the interpretation of the results, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for major aspects of the work.

FUNDING: No external funding.

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose.

     
  • CI

    confidence interval

  •  
  • COVID-19

    coronavirus disease 2019

  •  
  • HR

    hazard ratio

  •  
  • mRNA

    messenger ribonucleic acid

  •  
  • RT-PCR

    polymerase chain reaction

  •  
  • SARS-CoV-2

    severe acute respiratory syndrome coronavirus 2

  •  
  • VE

    vaccine effectiveness

1
World Health Organization (WHO)
.
COVID-19 dashboard
.
Available at: https://covid19.who.int. Accessed July 6, 2022
2
Chilamakuri
R
,
Agarwal
S
.
COVID-19: characteristics and therapeutics
.
Cells
.
2021
;
10
(
2
):
206
3
Liang
WH
,
Guan
WJ
,
Li
CC
, et al
.
Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China
.
Eur Respir J
.
2020
;
55
(
6
):
2000562
4
Borobia
AM
,
Carcas
AJ
,
Arnalich
F
, et al;
On Behalf Of The Covid Hulp Working Group
.
A cohort of patients with COVID-19 in a major teaching hospital in Europe
.
J Clin Med
.
2020
;
9
(
6
):
1733
5
Garnier-Crussard
A
,
Forestier
E
,
Gilbert
T
,
Krolak-Salmon
P
.
Novel coronavirus (COVID-19) epidemic: what are the risks for older patients?
J Am Geriatr Soc
.
2020
;
68
(
5
):
939
940
6
Mueller
AL
,
McNamara
MS
,
Sinclair
DA
.
Why does COVID-19 disproportionately affect older people?
Aging (Albany NY)
.
2020
;
12
(
10
):
9959
9981
7
Havers
FP
,
Whitaker
M
,
Self
JL
, et al;
COVID-NET Surveillance Team
.
Hospitalization of adolescents aged 12-17 years with laboratory-confirmed COVID-19 - COVID-NET, 14 States, March 1, 2020-April 24, 2021
.
MMWR Morb Mortal Wkly Rep
.
2021
;
70
(
23
):
851
857
8
Garazzino
S
,
Lo Vecchio
A
,
Pierantoni
L
, et al
.
Epidemiology, clinical features and prognostic factors of pediatric SARS-CoV-2 infection: results from an Italian multicenter study
.
Front Pediatr
.
2021
;
9
:
649358
9
Centers for Disease Control and Prevention (CDC) Health Advisory
.
Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19)
.
Available at: https://emergency.cdc.gov/han/2020/han00432.asp. Accessed May 3, 2022
10
Feldstein
LR
,
Tenforde
MW
,
Friedman
KG
, et al;
Overcoming COVID-19 Investigators
.
Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19
.
JAMA
.
2021
;
325
(
11
):
1074
1087
11
European Centre for Disease Prevention and Control (ECDC)
.
COVID-19 vaccine tracker
.
12
Centre for Disease Control and Prevention (CDC)
.
COVID data tracker
.
13
Frenck
RW
Jr
,
Klein
NP
,
Kitchin
N
, et al;
C4591001 Clinical Trial Group
.
Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents
.
N Engl J Med
.
2021
;
385
(
3
):
239
250
14
Craxì
L
,
Casuccio
A
,
Amodio
E
,
Restivo
V
.
Who should get COVID-19 vaccine first? A survey to evaluate hospital workers' opinion
.
Vaccines (Basel)
.
2021
;
9
(
3
):
189
15
Italian Medicines Agency (AIFA)
.
Comirnaty – BioNTech/Pfizer
.
Available at: https://www.aifa.gov.it/en/comirnaty. Accessed May 3, 2022
16
Italian Medicines Agency (AIFA)
.
Spikevax – vaccine Moderna mRNA-1273
.
Available at: https://www.aifa.gov.it/en/moderna. Accessed May 3, 2022
17
Istituto Superiore di Sanità COVID-19 Task Force
.
Epidemia COVID-19: aggiornamento nazionale 15 settembre 2021 – ore 12:00
.
18
Istituto Superiore di Sanità COVID-19 Task Force
.
Epidemia COVID-19: aggiornamento nazionale 5 gennaio 2022 – ore 12:00
.
19
Italian Minister of Health
.
Coronavirus, new record of almost 3,000 recoveries in one day
.
20
RStudio Team
.
RStudio: Integrated Development for R. RStudio
.
Boston, MA
:
PBC
;
2020
21
Leeb
RT
,
Price
S
,
Sliwa
S
, et al
.
COVID-19 trends among school-aged children - United States, March 1-September 19, 2020
.
MMWR Morb Mortal Wkly Rep
.
2020
;
69
(
39
):
1410
1415
22
Mehta
NS
,
Mytton
OT
,
Mullins
EWS
, et al
.
SARS-CoV-2 (COVID-19): what do we know about children? A systematic review
.
Clin Infect Dis
.
2020
;
71
(
9
):
2469
2479
23
Haas
EJ
,
Angulo
FJ
,
McLaughlin
JM
, et al
.
Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. [published correction appears in Lancet. 2021 Jul 17;398(10296): 212]
Lancet
.
2021
;
397
(
10287
):
1819
1829
24
Lutrick
K
,
Rivers
P
,
Yoo
YM
, et al
.
Interim estimate of vaccine effectiveness of BNT162b2 (Pfizer-BioNTech) vaccine in preventing SARS-CoV-2 infection among adolescents aged 12-17 Years – Arizona, July-December 2021
.
MMWR Morb Mortal Wkly Rep
.
2021
;
70
(
5152
):
1761
1765
25
Glatman-Freedman
A
,
Hershkovitz
Y
,
Kaufman
Z
,
Dichtiar
R
,
Keinan-Boker
L
,
Bromberg
M
.
Effectiveness of BNT162b2 vaccine in adolescents during outbreak of SARS-CoV-2 Delta variant infection, Israel, 2021
.
Emerg Infect Dis
.
2021
;
27
(
11
):
2919
2922
26
Amodio
E
,
Vella
G
,
Restivo
V
,
Casuccio
A
,
Vitale
F
;
On Behalf Of The Covid-Surveillance Working Group Of The University Of Palermo
.
Effectiveness of mRNA COVID-19 vaccination on SARS-CoV-2 infection and COVID-19 in Sicily over an eight-month period
.
Vaccines (Basel)
.
2022
;
10
(
3
):
426
27
Reis
BY
,
Barda
N
,
Leshchinsky
M
, et al
.
Effectiveness of BNT162b2 vaccine against Delta variant in adolescents
.
N Engl J Med
.
2021
;
385
(
22
):
2101
2103
28
Olson
SM
,
Newhams
MM
,
Halasa
NB
, et al;
Overcoming Covid-19 Investigators
.
Effectiveness of BNT162b2 vaccine against critical Covid-19 in adolescents
.
N Engl J Med
.
2022
;
386
(
8
):
713
723
29
Price
AM
,
Olson
SM
,
Newhams
MM
, et al;
Overcoming Covid-19 Investigators
.
BNT162b2 protection against the Omicron variant in children and adolescents
.
N Engl J Med
.
2022
;
386
(
20
):
1899
1909
30
Polack
FP
,
Thomas
SJ
,
Kitchin
N
, et al;
C4591001 Clinical Trial Group
.
Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine
.
N Engl J Med
.
2020
;
383
(
27
):
2603
2615
31
Amodio
E
,
Minutolo
G
,
Casuccio
A
, et al
.
Adverse reactions to anti-SARS-CoV-2 vaccine: a prospective cohort study based on an active surveillance system
.
Vaccines (Basel)
.
2022
;
10
(
3
):
345
32
Tartof
SY
,
Slezak
JM
,
Fischer
H
, et al
.
Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study
.
Lancet
.
2021
;
398
(
10309
):
1407
1416
33
Prunas
O
,
Weinberger
DM
,
Pitzer
VE
,
Gazit
S
,
Patalon
T
.
Waning effectiveness of the BNT162b2 vaccine against infection in adolescents. [published online ahead of print January 5, 2022]
medRxiv
.
doi:10.1101/2022.01.04.22268776
34
Andrews
N
,
Tessier
E
,
Stowe
J
, et al
.
Duration of protection against mild and severe disease by Covid-19 vaccines
.
N Engl J Med
.
2022
;
386
(
4
):
340
350
35
Ali
K
,
Berman
G
,
Zhou
H
, et al
.
Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents
.
N Engl J Med
.
2021
;
385
(
24
):
2241
2251
36
World Health Organization (WHO)
.
Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19: interim guidance, first issued 25 January 2021, updated 15 June 2021, updated 19 November 2021, updated 23 February 2022
.
Available at: https://apps.who.int/iris/handle/10665/352124. Accessed May 3, 2022