In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Since the introduction to the vaccination schedule of the Bacillus Calmette-Guerin (BCG) live attenuated vaccine directed towards tuberculosis prevention, a decrease in infant mortality has been reported, not related only to tuberculosis. BCG vaccine has been hypothesized to have a non-specific role towards other unrelated pathogens such as viruses that cause airway disease, with reduced morbidity and mortality. In murine as well as in human models it has been shown to decrease the incidence of acute respiratory influenza infections. Likewise, in countries with a high endemicity for tuberculosis, the BCG vaccine reduces the incidence of respiratory infections by up to 80% . In healthy subjects, the BCG vaccine increases the production of proinflammatory cytokines in monocytes. Likewise, it increases the epigenetic response, causing an increase in the transcription of genes important in the antimicrobial response, as well as an improvement in cellular function. This is the first national clinical trial to evaluate prospectively the effect that the BCG vaccine offers towards the prevention and reduction of severity in cases of COVID-19.
The study design is a randomized, double-blinded, placebo-controlled clinical trial. Age stratified randomization (\<45 years and\> 45 years) was performed using permuted blocks with allocation concealment. The sample size is 908 patients. 454 patients in each stratum (227 with placebo and 227 with BCG vaccine). Eligible participants will be healthcare professionals over 18 years of age who are in contact with patients with COVID-19, with negative IgG and IgM antibodies results for SARS-CoV-2 prior to their inclusion and sign the informed consent. After signing the informed consent, the participants will be randomized 1:1 to the intervention group (BCG vaccine) or control (placebo), a medical history will be performed, and a blood plasma sample will be obtained to determine specific antibodies against SARS-CoV-2. The patients will be followed up for 6 months after the application of the vaccine, they will be contacted by phone every two weeks in order to identify the adverse effects of the vaccine (30 days after the application) as well as to identify symptoms of COVID-19, in addition, follow-up visits will be carried out at the third and sixth months, in each of these visits a blood plasma sample will be obtained and IgG and IgM antibodies will be measured. Statistical Analysis Type: By intention to treatment
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
908
A single dose BCG vaccine intradermally (deltoid region of the right arm) 0.1 ml, equivalent to 0.075 mg of attenuated Mycobacterium bovis . (Tokio 172 strain)
A single dose intradermally ((deltoid region of the right arm) 0.1 ml of NaCl 0.9% solution
Hospital Universitario "José E. González"
Monterrey, Nuevo León, Mexico
Demonstrate COVID- 19 disease incidence among Health care workers:
Cumulative incidence of infection in 6 months: disease defined as positive SARS-Cov-2 test (serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Time frame: During the 6 months study period
Demonstrate cumulative incidence of hospitalization for COVID-19 among Health care workers:
Cumulative incidence of hospitalization for COVID-19
Time frame: During the 6 months study period
Demonstrate the Incidence of specific Antibodies against SARS-CoV-2 at 3 and 6 months in health care workers
Incidence of specific Antibodies (IgG and IgM) against SARS-CoV-2 will be measured at 3 and 6 months
Time frame: During the 6 months study period
Hospitalization of severe disease COVID-19
Number of participants who needed hospitalization
Time frame: During the 6 months study period
Oxygen supplementation in severe disease COVID-19
Number of participants who Need for oxygen supplementation (nasal cannulas, masks, high flow oxygen) in hospitalized patients
Time frame: During the 6 months study period
Need for intubation or non-invasive ventilation for the patient.
Number of participants who Need for intubation or non-invasive ventilation in hospitalized patients
Time frame: During the 6 months study period
Critical care admission with SARS-CoV2
Number of participants in Critical care admission with SARS-CoV2 in hospitalized patients
Time frame: During the 6 months study period
Mortality associated to progressive pulmonary disease
Mortality associated to progressive pulmonary disease in hospitalized patients
Time frame: During the 6 months study period
Evaluate the safety of the vaccine by measuring the incidence rates of local and systemic adverse effects that occur after one month its application.
Time frame: 1 month after vaccine/placebo application
Calculate the incidence of COVID-19 complications
Time frame: During the 6 months study period
Determine the mean days of hospitalization and days in intensive care unit by COIVD-19
Time frame: During the 6 months study period
Calculate the cost associated with in-hospital medical care
Time frame: During the 6 months study period
Determine the scores of the Clinical Prediction Rules associated with mortality using Sequential Organ Failure Assessment (SOFA score) at the patient's hospital admission:
SOFA score: PaO2/FIO2 (mm Hg), SaO2/FIO2, Platelets (×10³/µL), Bilirubin (mg/dL), Hypotension, Glasgow Coma Score and Creatinine (mg/dL) or urine output (mL/d).
Time frame: During the 6 months study period
Determine the scores of the Clinical Prediction Rules associated with mortality using Acute Physiology and Chronic Health disease Classification System (APACHE) at the patient's hospital admission:
APACHE: History of severe organ failure or immunocompromise Heart Failure Class IV, cirrhosis, chronic lung disease, or dialysis-dependent, Age, Temperature (C°), Mean arterial pressure (mmHg), pH, Sodium (mEq/L), Potassium (mEq/L), Creatinine (mg/dL), Hematocrit (%), WBC (x 109/L)
Time frame: During the 6 months study period
Evaluate and determine the alteration profile in laboratory studies at the patient's hospital admission
CPR, ESR, Ferritin, D-dimer, LDH,Troponins, Procalcitonin, Interleukin-6, Hemoglobin, Hematocrit, Erythrocytes, Leukocytes, MCV, HCM, MCHC, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, Glucose, Urea, Creatinine, BUN, Sodium, Potassium, Chlorine, Calcium, Serum albumin, Direct bilirubin, Indirect bilirubin, Alkaline phosphatase, AST, ALT, bleeding time, Prothrombin Time, Activated partial thromboplastin time, Arterial / Venous Blood Gasometry, pH, pCO2, HCO3, pO2, SaO2%, Lactate.
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Time frame: During the 6 months study period
Registration of chronic medications
Time frame: During the 6 months study period
Need for vasopressors
Time frame: During the 6 months study period