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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: 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

• Study Type: Observational
• Enrollment (Actual): 4574

Contacts and Locations

• Study Contact: Name: Regis Rosa, MD, PhD; Phone Number: +5551994538804; Email: regis.rosa@hmv.org.br

Study Locations

• Brazil
  • PR
    • Toledo, PR, Brazil
      • Unidade Básica de Saúde Jardim Cosmos
    • Toledo, PR, Brazil
      • Unidade de Pronto Atendimento Pediátrico Dr. José Ivo Alves da Rocha
  • Paraná
    • Toledo, Paraná, Brazil
      • Pronto Atendimento Municipal de Toledo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The present study population will be composed by individuals aged 12 years or older who seek the public healthcare system of Toledo city with symptoms suggestive COVID-19. 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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fully vaccinated with BNT162b2 COVID-19 vaccine; 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; Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine
Ever vaccinated with BNT162b2 COVID-19 vaccine; 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; Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine
Partially vaccinated with BNT162b2 COVID-19 vaccine; 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; Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine
Fully vaccinated with other available COVID-19 vaccines; Defined as fully vaccinated with available COVID-19 vaccines other than the BNT162b2 according to the manufacturer recommendations.	Drug: CoronaVac COVID-19 vaccine; CoronaVac COVID-19 vaccine; Drug: ChAdOx1 nCoV-19 Covid-19 Vaccine; ChAdOx1 nCoV-19 Covid-19 Vaccine; Drug: Ad26.COV2.S COVID-19 Vaccine; Ad26.COV2.S COVID-19 Vaccine
Never vaccinated; 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; 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; Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine; Drug: CoronaVac COVID-19 vaccine; CoronaVac COVID-19 vaccine; Drug: ChAdOx1 nCoV-19 Covid-19 Vaccine; ChAdOx1 nCoV-19 Covid-19 Vaccine; Drug: Ad26.COV2.S COVID-19 Vaccine; Ad26.COV2.S COVID-19 Vaccine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Moinhos de Vento
• Collaborators: Pfizer; Universidade Federal do Paraná; Inova Medical
• Investigators: Principal Investigator: Regis G Rosa, MD, PhD, Hospital Moinhos de Vento; Principal Investigator: Maicon Falavigna, MD, PhD, Hospital Moinhos de Vento

Publications and helpful links

General Publications

• Goulart Rosa R, Spinardi J, Allen KE, Manfio J, de Araujo CLP, Cohen M, Robinson CC, Sganzerla D, Ferreira D, de Souza EM, de Oliveira JC, Gradia DF, Brandalize APC, Kucharski GA, Pedrotti F, Rodrigues CO, Kyaw MH, Castillo GDCM, Srivastava A, McLaughlin JM, Falavigna M. BNT162b2 against COVID-19 in Brazil using a test-negative design: Study protocol and statistical analysis plan. PLoS One. 2022 Oct 20;17(10):e0276384. doi: 10.1371/journal.pone.0276384. eCollection 2022.
• Rosa RG, Falavigna M, Manfio JL, de Araujo CLP, Cohen M, do Valle Barbosa GRG, de Souza AP, Romeiro Silva FK, Sganzerla D, da Silva MMD, Ferreira D, de Oliveira Rodrigues C, de Souza EM, de Oliveira JC, Gradia DF, Brandalize APC, Royer CA, Luiz RM, Kucharski GA, Pedrotti F, Valluri SR, Srivastava A, Juliao VW, Melone OC, Allen KE, Kyaw MH, Spinardi J, Del Carmen Morales Castillo G, McLaughlin JM; Toledo BNT16b2 Study Group Investigators. BNT162b2 mRNA COVID-19 against symptomatic Omicron infection following a mass vaccination campaign in southern Brazil: A prospective test-negative design study. Vaccine. 2023 Aug 23;41(37):5461-5468. doi: 10.1016/j.vaccine.2023.07.038. Epub 2023 Jul 26.

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2021
• Primary Completion (Actual): June 20, 2022
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Mass vaccination
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: BNT162b2 in Toledo, Brazil

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes