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

Conditions

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

Keywords

BCG, Therapeutic Vaccine, COVID-19, SARS-CoV 2, Interferon Gamma, Immunoglobulin, Immunemodulation, Transmission

Brief summary

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

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.

Buosi K, Jalalizadeh M, Maia AR, Morari J, Velloso LA, Reis LO.

2024-07-161 citations

10.2147/ijgm.s468047

Healthcare Workers (HCWs) and non-HCWs reaction to Bacillus Calmette-Guérin (BCG) in the BATTLE trial.

Jalalizadeh M, Leme PAF, Buosi K, Dionato FAV, Dal Col LSB, Giacomelli CF, Reis LO.

2023-09-222 citations

10.1016/j.vaccine.2023.09.031

BCG vaccine safety in COVID-19 convalescent adults: BATTLE a randomized controlled trial.

Dionato FAV, Jalalizadeh M, Buosi K, Visacri MB, Dal Col LSB, Giacomelli CF, Leme PAF, Maia CL, Moriel P, Reis LO.

2022-06-2012 citations

10.1016/j.vaccine.2022.06.039

Randomized clinical trial of BCG vaccine in patients with convalescent COVID‐19: Clinical evolution, adverse events, and humoral immune response

Mehrsa Jalalizadeh, Keini Buosi, Franciele A. V. Dionato, Luciana S. B. Dal Col, Cristiane F. Giacomelli et al. (14 authors)

Journal of Internal Medicine2022-05-2319 citations

10.1111/joim.13523

Interventions

BIOLOGICALBCG

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

BIOLOGICALPlacebo

0.9% saline in the same volume as the BCG vaccine in a single dose

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Local and systemic adverse events to BCG vaccination	3 months	Classified according to type and severity

Other

Measure	Time frame	Description
SARS-CoV-2 elimination	21 days of symptoms onset or diagnosis	Virus detection by PCR
Seroconversion rate and titration	45 days of symptoms onset or diagnosis	Titration of anti SARS-CoV-2 IgA, IgM and IgG
Seroconversion rate	21 days of symptoms onset or diagnosis	Titration of anti SARS-CoV-2 IgA, IgM and IgG

Countries

Brazil

Outcome results

None listed