A Real-world Evidence Study of BNT162b2 mRNA Covid-19 Vaccine 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 following a mass vaccination campaign in the city of Toledo in Southern Brazil. Individuals aged 12 years or older who seek the public healthcare system with symptoms suggestive COVID-19 will be enrolled. Participants with a positive polymerase chain reaction (PCR) test for SARS-CoV-2 will be classified as cases, and those with negative PCR test for SARS-CoV-2 will be classified as controls. Cases will be followed-up for a period of one year by means of structured telephone interviews.

Official Title
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Effectiveness of Pfizer-BioNTech BNT162b2 mRNA COVID-19 Vaccine on Symptomatic SARS-CoV-2 Infection and COVID-19-related Hospitalizations, Mortality, and Long-term Consequences in Brazil: a Real-world Evidence Study

Conditions
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Covid19

Intervention / Treatment
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* Drug: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine
* Drug: CoronaVac COVID-19 vaccine
* Drug: ChAdOx1 nCoV-19 Covid-19 Vaccine
* Drug: Ad26.COV2.S COVID-19 Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 12 years old; 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 sample for SARS-CoV-2 diagnosis 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; Lack of consent to participate.

Ages Eligible for Study
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Minimum Age: 12 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 |
| --- | --- |
| Fully vaccinated with BNT162b2 COVID-19 vaccine<br>Defined as 2 doses of Pfizer/BioNTech BNT162b2 mRNA 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. | Drug: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>* Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>|
| Ever vaccinated with BNT162b2 COVID-19 vaccine<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. | Drug: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>* Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>|
| Partially vaccinated with BNT162b2 COVID-19 vaccine<br>Defined as 1 dose (only) of Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine received with ≥14 days between receipt of the 1st dose and ARI symptom onset. | Drug: 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 other than the BNT162b2 according to the manufacturer recommendations. | Drug: CoronaVac COVID-19 vaccine<br>* CoronaVac COVID-19 vaccine<br>Drug: ChAdOx1 nCoV-19 Covid-19 Vaccine<br>* ChAdOx1 nCoV-19 Covid-19 Vaccine<br>Drug: Ad26.COV2.S COVID-19 Vaccine<br>* Ad26.COV2.S 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. | |
| Fully vaccinated plus booster dose of BNT162b2 COVID-19 vaccine<br>Defined as fully vaccinated with available COVID-19 vaccines according to the manufacturer recommendations plus booster dose of BNT162b2 COVID-19 vaccine received with ≥14 days between receipt of the 1st dose and ARI symptom onset. | Drug: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>* Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine<br>Drug: CoronaVac COVID-19 vaccine<br>* CoronaVac COVID-19 vaccine<br>Drug: ChAdOx1 nCoV-19 Covid-19 Vaccine<br>* ChAdOx1 nCoV-19 Covid-19 Vaccine<br>Drug: Ad26.COV2.S COVID-19 Vaccine<br>* Ad26.COV2.S COVID-19 Vaccine<br>|

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 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 Gamma variant | Odds of symptomatic SARS-CoV-2 infection due to Gamma variant defined by the presence of symptoms suggestive COVID-19 with a positive PCR test for SARS-CoV-2 Gamma 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 PCR test for SARS-CoV-2 Alfa, Beta, or Delta variant | At the moment of enrollment | 
| Duration of COVID-19 symptoms | Length of COVID-19-related symptoms | within 180 days from enrollment | 
| Incidence of hospitalization due to COVID-19 | Incidence of hospital admission due to COVID-19 | Within 30 days from enrollment | 
| Incidence of ICU admission | Incidence of ICU admission | Within 30 days from enrollment | 
| Incidence of mechanical ventilation | Incidence of invasive mechanical ventilation | Within 30 days from enrollment | 
| Mortality due to COVID-19 | Incidence of COVID-19-related mortality | Within 90 days from enrollment | 
| Utility score of health-related quality of life at 3 months | Utility score of health-related quality of life assessed with the EuroQol- 5 dimensions 3-level questionnaire. The utility score derived from the descriptive system for the Brazilian population ranges from -0.176 (indicating the worst health status [serious problems in all domains]) to 1.0 (indicating the best health status [no problems at all]) | 90 days after enrollment | 
| Prevalence of long COVID-19 symptoms at 6 months | Incidence of long COVID-19-related symptoms (fatigue, muscular weakness, dyspnea, cough, loss of taste or smell, concentration or memory difficulties, sleep disorders, headache, anxiety, and depression) | 180 days after enrollment | 
| Incidence of new symptomatic COVID-19 infection | Incidence of new symptomatic COVID-19 infection defined as recurrence of COVID-19-related symptoms with a positive PCR test for SARS-CoV-2 90 days after the index infection | 365 days from enrollment | 
| Incidence of any vaccine-related adverse event | Incidence of any vaccine-related adverse event including local pain, hyperemia or necrosis; fever; fatigue; headache; myalgia; arthralgia; vomiting; diarrhea; and other symptoms | 365 days from enrollment | 
| Incidence of vaccine-related severe adverse event | Incidence of any adverse event that result in death, hospitalization or prolongation of hospitalization, and persistent or significant disability | 365 days from enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Mass vaccination