COVID-19Plus_BoosterNCT05283902
Effectiveness, Immunogenicity and Safety of the Second Booster Dose of the Vaccine Against COVID-19 in the Elderly
An observational study of COVID-19 and Vaccine Adverse Reaction, run by Federal University of Espirito Santo at 1 site in Brazil.
Trial summary
The objective of this observational case-crossover study is to evaluate the effectiveness, safety and immunogenicity of the second booster dose in the elderly. There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- COVID-19, Vaccine Adverse Reaction, Vaccine-Preventable Diseases
- What is being tested?
- ChAdOx1 nCoV-19 or Comirnaty or Janssen COVID-19 Vaccine
- Type of treatment
- Vaccines
- How many people
- 260 participants
- Where
- 1 siteBrazil
- Study dates
- 19 Mar 2022to 1 Oct 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and sixty participants, with quotas distributed by sex (50% male and 50% female) and age group, will be invited to participate in biological sample collection for the immunogenicity study, in a health unit in Cariacica-ES. This sub-sample will be compared with 240 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers.
Who may be able to join
- Age equal to or greater than 60 years
- Residents of Espírito Santo, Brazil
Who cannot join
- Being under active treatment (chemotherapy and/or radiotherapy) for the treatment of any type of neoplasm
- Being admitted to an institutionalization establishment for the elderly (hospitals, nursing homes, shelters or similar).
- Patients with mental illness with inability to understand the consent form
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effectiveness, Immunogenicity and Safety of the Second Booster Dose (Fourth Dose) of the Vaccine Against COVID-19 in the Elderly: Study Reforça Mais (Plus Booster)
The objective of this observational case-crossover study is to evaluate the effectiveness, safety and immunogenicity of the second booster dose in the elderly. There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and sixty participants will be invited to participate in biological sample for the immunogenicity study. This sub-sample will be compared with 260 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers. The main effectiveness outcome will be the number of hospitalizations; and secondary outcomes will be deaths, number of reported cases, number of cases confirmed by RT-PCR. The safety assessment will be carried out by monitoring adverse events. The cellular and humoral immune response will be evaluated by viral neutralization assay (search for neutralizing antibodies), serological assay by chemiluminescence, determination of specific IgM and IgG profile, dosage of soluble systemic factors (chemokines, cytokines and growth factors), stimulation in vitro antigen-specific peripheral blood mononuclear cells and investigation of memory T and B lymphocytes and intracytoplasmic cytokines. The study hypothesis is that elderly people who received the second booster dose have a lower incidence rate of hospitalizations and death than those who received the primary regimen (two doses or one of Janssen) or a booster dose, and that the immune response humoral and cellular function of the elderly is similar to those who are immunosuppressed.
Read the detailed description
Faced with the new scenario of high transmission of the Ômicron variant of SARS-COV-2, in which the elderly over 60 years and immunosuppressed even vaccinated with three doses have become a population vulnerable to a greater probability of serious illness by Covid-19, demanding an increase in risk of hospitalization and deaths, the application of the fourth dose (second booster dose) has become an alternative to increase protection for these individuals. The general objective of this study is to evaluate the effectiveness, safety and immunogenicity of the second booster dose in the elderly. This is an observational, case-crossover study, based on databases with notification and vaccination records and a cohort study for the analysis of immunogenicity. Elderly people of both sexes aged 60 years or older, residents of Espírito Santo, will be included. There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and sixty participants, with quotas distributed by sex (50% male and 50% female) and age group, will be invited to participate in biological sample collection on the day of application of the second booster dose (T1) , 28 days after the second booster dose (T2), at the follow-up visit after 3 months (T3), 150 days (T4) and 180 days (T5), for follow-up of vaccine response and follow-up of duration of immunity, in a health unit in Cariacica-ES. This sub-sample will be compared with 240 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers. The main effectiveness outcome will be the number of hospitalizations, weighted by protection time, 90 days after complete immunization (14th day after second booster dose); and secondary outcomes will be deaths, number of reported cases, number of cases confirmed by RT-PCR. The safety assessment will be carried out by monitoring adverse events. The cellular and humoral immune response will be evaluated by viral neutralization assay (search for neutralizing antibodies), serological assay by chemiluminescence, determination of specific IgM and IgG profile, dosage of soluble systemic factors (chemokines, cytokines and growth factors), stimulation in vitro antigen-specific peripheral blood mononuclear cells and investigation of memory T and B lymphocytes and intracytoplasmic cytokines. The study hypothesis is that elderly people who received the second booster dose have a lower incidence rate of hospitalizations and death than those who received the primary regimen (two doses or one of Janssen) or a booster dose, and that the immune response humoral and cellular function of the elderly is similar to those who are immunosuppressed.
- Being tested
- ChAdOx1 nCoV-19 or Comirnaty or Janssen COVID-19 Vaccine
- Medical subject headings
- COVID-19, Vaccine-Preventable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChAdOx1 nCoV-19 or Comirnaty or Janssen COVID-19 VaccineBiological
In a Technical Note, the State of Espírito Santo decided to recommend the application of the fourth dose with vaccines using messenger RNA (mRNA) technology or viral vector vaccine, for all people aged 60 years or older, with an interval of 90 days from of the third dose, considering that, while there is no availability of vaccines adapted to the new variants, boosters with available vaccines are still the most appropriate ways to prevent hospitalization and deaths.
| Study group | Role | What they receive |
|---|---|---|
| Elderly group - Immunogenicity | 260 participants from the Effectiveness group, with quotas distributed by sex (50% male and 50% female) and age group, will be invited to participate in biological sample collection for the immunogenicity study. Receives: Biological: ChAdOx1 nCoV-19 or Comirnaty or Janssen COVID-19 Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of hospital admissions
number of hospital admissions for covid-19 recorded in the "e-SUS notifica"
Measured: Change from baseline at 6 months
Number of adverse events
Surveillance of adverse post-vaccine events (PVAE) and adverse events of special interest (EAIE) recorded in the "e-SUS notifica"
Measured: Change from baseline at 1 month
Secondary outcomes (7)
number of deaths
Number of deaths with specific ICD for covid-19 recorded in the "e-SUS notifica"
Measured: Change from baseline at 6 months
number of Covid-19 cases
number of Covid-19 cases confirmed by RT-PCR recorded in the "e-SUS notifica"
Measured: Change from baseline at 6 monhts
Viral neutralization assay
Neutralizing antibody titers will be expressed by the ability of antibodies to neutralize up to 50% the number of plaques (PRNT50). Title > 1:50 will be considered positive.
Measured: Change from baseline at 1, 3, 5 and 6 months
Serological assay
Serological test by chemiluminescence for qualitative and quantitative determination of specific IgG antibodies against the nucleocapsid protein of SARS-Cov-2. Results are expressed in U/mL and data interpretation will be done as follows: <0.8 U/mL = non-reactive sample; ≥0.8 U/mL = reactive sample.
Measured: Change from baseline at 1, 3, 5 and 6 months
Soluble systemic factors
Dosage of soluble systemic factors (chemokines, cytokines and growth factors). Results will be expressed in pg/ml.
Measured: Change from baseline at 1, 3, 5 and 6 months
Lymphocyte investigation
Investigation of memory T and B lymphocytes. The results will be expressed in percentage positive frequency for a specific cell phenotype.
Measured: Change from baseline at 1, 3, 5 and 6 months
Cytokine investigation
Investigation of intracytoplasmic cytokines. The results will be expressed in percentage positive frequency for a specific cell phenotype.
Measured: Change from baseline at 1, 3, 5 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2022
- Study start19 Mar 2022
- Primary completion1 Jun 2022
- Study completion1 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 260 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of Espirito Santo
- Sponsor type
- University, hospital or other
- Collaborators
- Secretaria de Estado da Saúde do Espírito Santo - SESA, Instituto René Rachou (IRR)
- Responsible party
- Principal investigator, Valéria Valim, Federal University of Espirito Santo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05283902
- Sponsor's protocol ID
- FUES05
- Acronym
- Plus_Booster
- Status last verified
- Mar 2026
- First submitted
- 10 Mar 2022
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness, Immunogenicity and Safety of the Second Booster Dose (Fourth Dose) of the Vaccine Against COVID-19 in the Elderly: Study Reforça Mais (Plus Booster)
- ClinicalTrials.gov ID
- NCT05283902
- Acronym / sponsor ID
- Plus_Booster / FUES05
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 260 participants (actual)
- Lead sponsor
- Federal University of Espirito SantoUniversity, hospital or other
- Collaborators
- Secretaria de Estado da Saúde do Espírito Santo - SESA, Instituto René Rachou (IRR)
- Study start
- 19 Mar 2022 (actual)
- Primary completion
- 1 Jun 2022 (actual)
- Study completion
- 1 Oct 2022 (actual)
- First posted
- 17 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this observational case-crossover study is to evaluate the effectiveness, safety and immunogenicity of the second booster dose in the elderly. There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and sixty participants will be invited to participate in biological sample for the immunogenicity study. This sub-sample will be compared with 260 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers. The main effectiveness outcome will be the number of hospitalizations; and secondary outcomes will be deaths, number of reported cases, number of cases confirmed by RT-PCR. The safety assessment will be carried out by monitoring adverse events. The cellular and humoral immune response will be evaluated by viral neutralization assay (search for neutralizing antibodies), serological assay by chemiluminescence, determination of specific IgM and IgG profile, dosage of soluble systemic factors (chemokines, cytokines and growth factors), stimulation in vitro antigen-specific peripheral blood mononuclear cells and investigation of memory T and B lymphocytes and intracytoplasmic cytokines. The study hypothesis is that elderly people who received the second booster dose have a lower incidence rate of hospitalizations and death than those who received the primary regimen (two doses or one of Janssen) or a booster dose, and that the immune response humoral and cellular function of the elderly is similar to those who are immunosuppressed.
Detailed description
Faced with the new scenario of high transmission of the Ômicron variant of SARS-COV-2, in which the elderly over 60 years and immunosuppressed even vaccinated with three doses have become a population vulnerable to a greater probability of serious illness by Covid-19, demanding an increase in risk of hospitalization and deaths, the application of the fourth dose (second booster dose) has become an alternative to increase protection for these individuals. The general objective of this study is to evaluate the effectiveness, safety and immunogenicity of the second booster dose in the elderly. This is an observational, case-crossover study, based on databases with notification and vaccination records and a cohort study for the analysis of immunogenicity. Elderly people of both sexes aged 60 years or older, residents of Espírito Santo, will be included. There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and sixty participants, with quotas distributed by sex (50% male and 50% female) and age group, will be invited to participate in biological sample collection on the day of application of the second booster dose (T1) , 28 days after the second booster dose (T2), at the follow-up visit after 3 months (T3), 150 days (T4) and 180 days (T5), for follow-up of vaccine response and follow-up of duration of immunity, in a health unit in Cariacica-ES. This sub-sample will be compared with 240 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers. The main effectiveness outcome will be the number of hospitalizations, weighted by protection time, 90 days after complete immunization (14th day after second booster dose); and secondary outcomes will be deaths, number of reported cases, number of cases confirmed by RT-PCR. The safety assessment will be carried out by monitoring adverse events. The cellular and humoral immune response will be evaluated by viral neutralization assay (search for neutralizing antibodies), serological assay by chemiluminescence, determination of specific IgM and IgG profile, dosage of soluble systemic factors (chemokines, cytokines and growth factors), stimulation in vitro antigen-specific peripheral blood mononuclear cells and investigation of memory T and B lymphocytes and intracytoplasmic cytokines. The study hypothesis is that elderly people who received the second booster dose have a lower incidence rate of hospitalizations and death than those who received the primary regimen (two doses or one of Janssen) or a booster dose, and that the immune response humoral and cellular function of the elderly is similar to those who are immunosuppressed.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Elderly group - Immunogenicity | – | Biological: ChAdOx1 nCoV-19 or Comirnaty or Janssen COVID-19 Vaccine260 participants from the Effectiveness group, with quotas distributed by sex (50% male and 50% female) and age group, will be invited to participate in biological sample collection for the immunogenicity study. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and sixty participants, with quotas distributed by sex (50% male and 50% female) and age group, will be invited to participate in biological sample collection for the immunogenicity study, in a health unit in Cariacica-ES. This sub-sample will be compared with 240 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers.
Key inclusion criteria (2 listed)
- Age equal to or greater than 60 years
- Residents of Espírito Santo, Brazil
Key exclusion criteria (3 listed)
- Being under active treatment (chemotherapy and/or radiotherapy) for the treatment of any type of neoplasm
- Being admitted to an institutionalization establishment for the elderly (hospitals, nursing homes, shelters or similar).
- Patients with mental illness with inability to understand the consent form
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChAdOx1 nCoV-19 or Comirnaty or Janssen COVID-19 VaccineIn a Technical Note, the State of Espírito Santo decided to recommend the application of the fourth dose with vaccines using messenger RNA (mRNA) technology or viral vector vaccine, for all people aged 60 years or older, with an interval of 90 days from of the third dose, considering that, while there is no availability of vaccines adapted to the new variants, boosters with available vaccines are still the most appropriate ways to prevent hospitalization and deaths. | Biological | Elderly group - Immunogenicity |
Primary outcome
number of hospital admissions
Time frame: Change from baseline at 6 months
number of hospital admissions for covid-19 recorded in the "e-SUS notifica"
Number of adverse events
Time frame: Change from baseline at 1 month
Surveillance of adverse post-vaccine events (PVAE) and adverse events of special interest (EAIE) recorded in the "e-SUS notifica"
7 secondary outcomes
number of deaths
Time frame: Change from baseline at 6 months
number of Covid-19 cases
Time frame: Change from baseline at 6 monhts
Viral neutralization assay
Time frame: Change from baseline at 1, 3, 5 and 6 months
Serological assay
Time frame: Change from baseline at 1, 3, 5 and 6 months
Soluble systemic factors
Time frame: Change from baseline at 1, 3, 5 and 6 months
Lymphocyte investigation
Time frame: Change from baseline at 1, 3, 5 and 6 months
Cytokine investigation
Time frame: Change from baseline at 1, 3, 5 and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 and Vaccine Adverse Reaction, run by Federal University of Espirito Santo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of hospital admissions (time frame: Change from baseline at 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.