A Real-world Evidence Study of BNT162b2 mRNA Covid-19 Vaccine Among Children in Brazil

Study Overview
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Brief Summary
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The present test-negative design study aims to estimate the real-world effectiveness of Pfizer-BioNTech BNT162b2 mRNA vaccine on symptomatic SARS-CoV-2 infection and its consequences among children aged 5 to 11 years in the city of Toledo in Southern Brazil. Individuals aged 5 to 11 years who seek the public healthcare system with symptoms suggestive COVID-19 will be enrolled. Participants with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 will be classified as cases, and those with negative RT-PCR test for SARS-CoV-2 will be classified as controls. Cases will be followed-up for a period of 3 months by means of structured telephone interviews.

Official Title
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A Real-world Evidence Study of BNT162b2 mRNA Covid-19 Vaccine Among Children Aged 5 to 11 Years in Brazil

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine
* Biological: CoronaVac COVID-19 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 5 and 11 years; Resident of Toledo city; Seeking care in the public healthcare system with symptoms suggestive of COVID-19 defined as follows: 1) ARI symptoms (nasal congestion, rhinorrhea, anosmia, sore throat, hoarseness, new or increased-from-baseline cough, sputum production, dyspnea, wheezing, myalgia) OR 2) Admitting diagnosis suggestive of ARI (pneumonia, upper respiratory infection, bronchitis, influenza, cough, asthma, viral respiratory illness, respiratory distress, AND/OR respiratory failure). Nasal or nasopharyngeal sample for SARS-CoV-2 test obtained as standard of care. Exclusion Criteria: SARS-CoV-2-directed antiviral treatment within the past 30 days; COVID-19 monoclonal antibody therapy within the past 90 days; COVID-19 convalescent serum therapy within the past 90 days; Failure to perform RT-PCR for diagnosis of SARS-CoV-2 infection.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Two doses or more of BNT162b2<br>Defined as ≥ 2 doses of BNT162b2 COVID-19 vaccine received with ≥7 days between receipt of the 2nd dose and acute respiratory illness (ARI) symptom onset. This group will serve as the 'exposed' group evaluated in the primary objective. | Biological: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>* Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>|
| One dose of BNT162b2<br>Defined as 1 dose (only) of Pfizer/BioNTech BNT162b2 COVID-19 vaccine received with ≥14 days between receipt of the 1st dose and ARI symptom onset. | Biological: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>* Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>|
| One dose or more of BNT162b2<br>Defined as ≥1 dose of Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine received with ≥14 days between receipt of the 1st dose and ARI symptom onset. | Biological: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>* Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>|
| Two doses of BNT162b2<br>Defined as 2 doses of BNT162b2 COVID-19 vaccine received with ≥7 days between receipt of the 2nd dose and acute respiratory illness (ARI) symptom onset. | Biological: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>* Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>|
| Three doses of BNT162b2<br>Defined as 3 doses of BNT162b2 COVID-19 vaccine received with ≥7 days between receipt of the 3rd dose and acute respiratory illness (ARI) symptom onset. | Biological: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>* Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>|
| Fully vaccinated with other available COVID-19 vaccines<br>Defined as fully vaccinated with available COVID-19 vaccines according to Brazil National Immunization Program recommendations. | Biological: CoronaVac COVID-19 vaccine<br>* CoronaVac COVID-19 vaccine<br>|
| Never vaccinated<br>Defined as never received any COVID-19 vaccine. This group will serve as the reference exposure group (i.e., 'unexposed' group) in all vaccine effectiveness analyses. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Odds of symptomatic SARS-CoV-2 infection | Odds of symptomatic SARS-CoV-2 infection defined by the presence of symptoms suggestive COVID-19 with a positive RT-PCR test for SARS-CoV-2. Symptoms suggestive of COVID-19 are defined as follows: 1) Acute respiratory illness symptoms (nasal congestion, rhinorrhea, anosmia, sore throat, hoarseness, new or increased-from-baseline cough, sputum production, dyspnea, wheezing, myalgia) OR 2) Admitting diagnosis suggestive of ARI (pneumonia, upper respiratory infection, bronchitis, influenza, cough, asthma, viral respiratory illness, respiratory distress, AND/OR respiratory failure). | At the moment of enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Odds of symptomatic SARS-CoV-2 infection due to Omicron variant | Odds of symptomatic SARS-CoV-2 infection due to Omicron variant defined by the presence of symptoms suggestive COVID-19 with a positive RT-PCR test for SARS-CoV-2 Omicron variant | At the moment of enrollment | 
| Odds of symptomatic SARS-CoV-2 infection due to other circulating variants of concern | Odds of symptomatic SARS-CoV-2 infection due to other circulating variants of concern defined by the presence of symptoms suggestive COVID-19 with a positive RT-PCR test for SARS-CoV-2 variants of concern. | At the moment of enrollment | 
| Duration of COVID-19 symptoms | Length of COVID-19-related symptoms | within 90 days from enrollment | 
| Incidence of hospitalization due to COVID-19 | Incidence of hospital admission due to COVID-19 | Within 90 days from enrollment | 
| Incidence of PICU admission | Incidence of Pediatric intensive care unit admission | Within 90 days from enrollment | 
| Incidence of invasive mechanical ventilation | Incidence of invasive mechanical ventilation | Within 90 days from enrollment | 
| Incidence of multisystem inflammatory syndrome | Incidence of multisystem inflammatory syndrome | Within 90 days from enrollment | 
| Mortality due to COVID-19 | Incidence of COVID-19-related mortality | Within 90 days from enrollment | 
| Prevalence of long COVID-19 symptoms at 3 months | Prevalence of long COVID-19-related symptoms (fatigue, muscular weakness, dyspnea, cough, loss of taste or smell, concentration or memory difficulties, sleep disorders, headache) | Within 90 days from enrollment |