COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement

Study Overview
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Brief Summary
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To date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).

Detailed Description
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Prospective, randomized, double-blind, multicentre study with international design collaboration with central clinical and mechanistic outcomes with public health implications both epidemiological and therapeutic in the context of the pandemic of COVID-19, an emerging disease, which quickly disrupted health services including Brazil's Unified Health System (SUS), as well as the entire productive force and economy worldwide. Because it is recent, the basic evidence related to infection, such as incubation period, time of transmissibility, and seroconversion, is little known and the proposal's goals have the potential to redirect the vaccine. Exploring bacillus Calmette Guerin (BCG) that presents significant potential for immune activation, with recognized safety in decades of previous experience and clear potential in the context under analysis, with low cost and available, ensuring wide accessibility, especially in the context of SUS, on which it depends especially the most vulnerable portion of the Brazilian population, notably in the COVID-19 pandemic. Non-specific effects of BCG caused by monocyte epigenetic reprogramming may result in increased production of pro-inflammatory cytokines, conferring innate (trained) immunity and protection against viral infections, including SARS-CoV-2 with the potential to positively impact clinical evolution, viral elimination, and seroconversion of COVID-19 patients.

Official Title
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COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement

Conditions
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COVID-19, BCG, Therapeutic Vaccine, SARS-CoV 2, Transmission

Intervention / Treatment
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* Biological: BCG
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years of age; laboratory or clinical-epidemiological confirmation of COVID-19 (history of close or home contact with a laboratory-confirmed case who has fever or at least one of the respiratory signs or symptoms, in the last 14 days after contact, and for which it was not possible to carry out the specific laboratory investigation) Exclusion Criteria: Immunosuppressed patients of any kind; Pregnant women; More than 14 days from the onset of symptoms; Not accept participation or non-signature of the IC; Undiagnosed cases, suspected or probable.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BCG vaccine<br>BCG Group (n = 200): 0.1 ml of lyophilized, live, and attenuated BCG intradermal vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose. | Biological: BCG<br>* 0.1 ml of lyophilized, live and attenuated intradermal BCG vaccine, containing between 2 and 8 x 1.000.000 C.F.U in a single dose<br>* Other names: Calmette Guerin bacillus;|
| Placebo Comparator: Placebo<br>Placebo group (n = 200): 0.9% saline solution in the same volume as BCG vaccine in a single dose. | Biological: Placebo<br>* 0.9% saline in the same volume as the BCG vaccine in a single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical evolution of COVID-19 | Classified as mild, moderate and severe | 45 days of symptoms onset or diagnosis | 
| SARS-CoV-2 elimination | Virus detection by PCR | 7 days of symptoms onset or diagnosis | 
| Seroconversion rate and titration | Titration of anti SARS-CoV-2 IgA, IgM and IgG | 7 days of symptoms onset or diagnosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local and systemic adverse events to BCG vaccination | Classified according to type and severity | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCG, Therapeutic Vaccine, COVID-19, SARS-CoV 2, Interferon Gamma, Immunoglobulin, Immunemodulation, Transmission