tetano
Editor, Senior Moderator
Infect Dis Ther
. 2022 Oct 15.
doi: 10.1007/s40121-022-00703-y. Online ahead of print.
Efficacy of Bacillus Calmette-Guérin (BCG) Vaccination in Reducing the Incidence and Severity of COVID-19 in High-Risk Population (BRIC): a Phase III, Multi-centre, Quadruple-Blind Randomised Control Trial
Sanjeev Sinha[SUP] 1 [/SUP], Anuj Ajayababu[SUP] 2 [/SUP], Himanshu Thukral[SUP] 2 [/SUP], Sushil Gupta[SUP] 3 [/SUP], Subhasish Kamal Guha[SUP] 4 [/SUP], Ayan Basu[SUP] 5 [/SUP], Gaurav Gupta[SUP] 2 [/SUP], Prashant Thakur[SUP] 3 [/SUP], Raghavendra Lingaiah[SUP] 6 [/SUP], Bimal Kumar Das[SUP] 7 [/SUP], Urvashi B Singh[SUP] 7 [/SUP], Ravinder Singh[SUP] 7 [/SUP], Rajiv Narang[SUP] 8 [/SUP], Dipankar Bhowmik[SUP] 9 [/SUP], Naveet Wig[SUP] 2 [/SUP], Dolan Champa Modak[SUP] 4 [/SUP], Bhaswati Bandyopadhyay[SUP] 10 [/SUP], Banya Chakrabarty[SUP] 11 [/SUP], Aditya Kapoor[SUP] 12 [/SUP], Satyendra Tewari[SUP] 12 [/SUP], Narayan Prasad[SUP] 13 [/SUP], Zia Hashim[SUP] 14 [/SUP], Alok Nath[SUP] 14 [/SUP], Niraj Kumari[SUP] 6 [/SUP], Ravinder Goswami[SUP] 15 [/SUP], Shivam Pandey[SUP] 16 [/SUP], Ravindra Mohan Pandey[SUP] 16 [/SUP]
Affiliations
Abstract
Introduction: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection.
Methods: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol.
Results: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection.
Conclusions: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study.
Clinical trials registry: Clinical Trials Registry India (CTRI/2020/07/026668).
Keywords: BCG vaccination; Incidence of COVID-19; Severe COVID-19; Symptomatic COVID-19; Vaccine efficacy.
. 2022 Oct 15.
doi: 10.1007/s40121-022-00703-y. Online ahead of print.
Efficacy of Bacillus Calmette-Guérin (BCG) Vaccination in Reducing the Incidence and Severity of COVID-19 in High-Risk Population (BRIC): a Phase III, Multi-centre, Quadruple-Blind Randomised Control Trial
Sanjeev Sinha[SUP] 1 [/SUP], Anuj Ajayababu[SUP] 2 [/SUP], Himanshu Thukral[SUP] 2 [/SUP], Sushil Gupta[SUP] 3 [/SUP], Subhasish Kamal Guha[SUP] 4 [/SUP], Ayan Basu[SUP] 5 [/SUP], Gaurav Gupta[SUP] 2 [/SUP], Prashant Thakur[SUP] 3 [/SUP], Raghavendra Lingaiah[SUP] 6 [/SUP], Bimal Kumar Das[SUP] 7 [/SUP], Urvashi B Singh[SUP] 7 [/SUP], Ravinder Singh[SUP] 7 [/SUP], Rajiv Narang[SUP] 8 [/SUP], Dipankar Bhowmik[SUP] 9 [/SUP], Naveet Wig[SUP] 2 [/SUP], Dolan Champa Modak[SUP] 4 [/SUP], Bhaswati Bandyopadhyay[SUP] 10 [/SUP], Banya Chakrabarty[SUP] 11 [/SUP], Aditya Kapoor[SUP] 12 [/SUP], Satyendra Tewari[SUP] 12 [/SUP], Narayan Prasad[SUP] 13 [/SUP], Zia Hashim[SUP] 14 [/SUP], Alok Nath[SUP] 14 [/SUP], Niraj Kumari[SUP] 6 [/SUP], Ravinder Goswami[SUP] 15 [/SUP], Shivam Pandey[SUP] 16 [/SUP], Ravindra Mohan Pandey[SUP] 16 [/SUP]
Affiliations
- PMID: 36242739
- DOI: 10.1007/s40121-022-00703-y
Abstract
Introduction: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection.
Methods: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol.
Results: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection.
Conclusions: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study.
Clinical trials registry: Clinical Trials Registry India (CTRI/2020/07/026668).
Keywords: BCG vaccination; Incidence of COVID-19; Severe COVID-19; Symptomatic COVID-19; Vaccine efficacy.