Sanjeev Sinha1, Anuj Ajayababu2, Himanshu Thukral2, Sushil Gupta3, Subhasish Kamal Guha4, Ayan Basu5, Gaurav Gupta2, Prashant Thakur3, Raghavendra Lingaiah6, Bimal Kumar Das7, Urvashi B Singh7, Ravinder Singh7, Rajiv Narang8, Dipankar Bhowmik9, Naveet Wig2, Dolan Champa Modak4, Bhaswati Bandyopadhyay10, Banya Chakrabarty11, Aditya Kapoor12, Satyendra Tewari12, Narayan Prasad13, Zia Hashim14, Alok Nath14, Niraj Kumari6, Ravinder Goswami15, Shivam Pandey16, Ravindra Mohan Pandey16. 1. Department of Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India. drsanjeevsinha@gmail.com. 2. Department of Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India. 3. Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow, UP, India. 4. School of Tropical Medicine (STM), Kolkata, India. 5. Department of Infectious Diseases, Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, India. 6. Department of Pathology, SGPGI, Lucknow, UP, India. 7. Department of Microbiology, AIIMS, New Delhi, India. 8. Department of Cardiology, AIIMS, New Delhi, India. 9. Department of Nephrology, AIIMS, New Delhi, India. 10. Unit of Virology, Department of Microbiology, STM, Kolkata, India. 11. Department of Microbiology, STM, Kolkata, India. 12. Department of Cardiology, SGPGI, Lucknow, UP, India. 13. Department of Nephrology, SGPGI, Lucknow, UP, India. 14. Department of Pulmonary Medicine, SGPGI, Lucknow, UP, India. 15. Department of Endocrinology, AIIMS, New Delhi, India. 16. Department of Biostatistics, AIIMS, New Delhi, India.
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).
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).
Authors: Caryn M Upton; Rob C van Wijk; Laurynas Mockeliunas; Ulrika S H Simonsson; Kirsten McHarry; Gerben van den Hoogen; Chantal Muller; Arné von Delft; Helene-Mari van der Westhuizen; Reinout van Crevel; Gerhard Walzl; Pedro M Baptista; Jonathan Peter; Andreas H Diacon Journal: EClinicalMedicine Date: 2022-05-12
Authors: Jona Walk; L Charlotte J de Bree; Wouter Graumans; Rianne Stoter; Geert-Jan van Gemert; Marga van de Vegte-Bolmer; Karina Teelen; Cornelus C Hermsen; Rob J W Arts; Marije C Behet; Farid Keramati; Simone J C F M Moorlag; Annie S P Yang; Reinout van Crevel; Peter Aaby; Quirijn de Mast; André J A M van der Ven; Christine Stabell Benn; Mihai G Netea; Robert W Sauerwein Journal: Nat Commun Date: 2019-02-20 Impact factor: 14.919
Authors: Hanna Czajka; Paweł Zapolnik; Łukasz Krzych; Wojciech Kmiecik; Lidia Stopyra; Anna Nowakowska; Teresa Jackowska; Dorota Darmochwał-Kolarz; Henryk Szymański; Igor Radziewicz-Winnicki; Artur Mazur Journal: Vaccines (Basel) Date: 2022-02-17
Authors: Merryn Voysey; Sue Ann Costa Clemens; Shabir A Madhi; Lily Y Weckx; Pedro M Folegatti; Parvinder K Aley; Brian Angus; Vicky L Baillie; Shaun L Barnabas; Qasim E Bhorat; Sagida Bibi; Carmen Briner; Paola Cicconi; Elizabeth A Clutterbuck; Andrea M Collins; Clare L Cutland; Thomas C Darton; Keertan Dheda; Christina Dold; Christopher J A Duncan; Katherine R W Emary; Katie J Ewer; Amy Flaxman; Lee Fairlie; Saul N Faust; Shuo Feng; Daniela M Ferreira; Adam Finn; Eva Galiza; Anna L Goodman; Catherine M Green; Christopher A Green; Melanie Greenland; Catherine Hill; Helen C Hill; Ian Hirsch; Alane Izu; Daniel Jenkin; Carina C D Joe; Simon Kerridge; Anthonet Koen; Gaurav Kwatra; Rajeka Lazarus; Vincenzo Libri; Patrick J Lillie; Natalie G Marchevsky; Richard P Marshall; Ana V A Mendes; Eveline P Milan; Angela M Minassian; Alastair McGregor; Yama F Mujadidi; Anusha Nana; Sherman D Padayachee; Daniel J Phillips; Ana Pittella; Emma Plested; Katrina M Pollock; Maheshi N Ramasamy; Adam J Ritchie; Hannah Robinson; Alexandre V Schwarzbold; Andrew Smith; Rinn Song; Matthew D Snape; Eduardo Sprinz; Rebecca K Sutherland; Emma C Thomson; M Estée Török; Mark Toshner; David P J Turner; Johan Vekemans; Tonya L Villafana; Thomas White; Christopher J Williams; Alexander D Douglas; Adrian V S Hill; Teresa Lambe; Sarah C Gilbert; Andrew J Pollard Journal: Lancet Date: 2021-02-19 Impact factor: 79.321