Study of BCG Vaccination status of COVID-19 infected patients & its relationship to morbidity, mortality & treatment outcome of the COVID-19 disease
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Abstract
There have been 760 million cases and 6.9 million recorded deaths worldwide due to COVID-19 infection since December 2019. The actual number is thought to be considerably higher (WHO) than documented worldwide. There was worldwide desperate search for ways to prevent the morbidities and mortalities associated with COVID-19 infection. In this context, BCG vaccination hypothesized to play both preventive as well as protective role against COVID-19 infection. All over the world many trials, ongoing or completed done with different results. According to South African trial conducted amongst 1000 healthcare workers, BCG revaccination stated to have no protective effect. On the other hand, trial in UK stated BCG effect to be dependent on ethnicity or race of infected individual.
Present study aim was to study, compare & analyse the proportion of BCG vaccinated among the COVID-19 patients. Severity of infection, disease progression, mortality, morbidity and duration of recovery or discharge were studied in both prospective & retrospective direction in 549 participants 1keeping in view their BCG vaccination status. The study is an effort to substantiate or refute claims of various studies published regarding BCG vaccination & COVID-19 infections.
Amongst the participants, 27.5% were found to be BCG vaccinated, while 72.5 % were unvaccinated. Majority of patients (50.4%) were with mild COVID-19 infection. The patients affected were mostly of 26-30 years (26.7%) of age. Patients of 36-40 years (2.1%) were from severe disease category.
An association was found between age group (‘p’ value < 0.05) and between genders (‘p’ value < 0.05) and BCG vaccination status. There were no association between gender and severity of COVID-19 infection. Amongst the patients with severe disease, 70% were not vaccinated for BCG. There was an association between the severity of the disease and the BCG vaccination status (‘p’ value<0.05). Respiratory symptoms were common amongst almost all the participants (95.8%). Amongst patients who were BCG vaccinated, none were on invasive ventilation therapy yet amongst the non-BCG vaccinated patients, 2.76% were on invasive ventilation. There was a significant association between BCG status and complications (‘p’ value < 0.05). The association between inflammatory markers with BCG status was also found to be significant (‘p’ value < 0.05).
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References
2. Gong W, Mao Y, Li Y, Qi Y. BCG Vaccination: A potential tool against COVID-19 and COVID-19-like Black Swan incidents. Int Immunopharmacol. 2022 Jul;108:108870. doi: 10.1016/j.intimp.2022.1 08870. Epub 2022 May 17. PMID: 35597119; PMCID: PMC9113676.
3. Singh AK, Netea MG, Bishai WR. BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases. J Clin Invest. 2021 Jun 1;131(11):e148291. doi: 10.1172/JCI148291. PMID : 34060492; PMCID: PMC8159679.
4. Evangelos J. Giamarellos-Bourboulis, Maria Tsilika, Simone Moorlag, Nikolaos Antonakos, Antigone Kotsaki, et al. Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly, Cell, Volume 183, Issue 2, 2020, Pages 315-323.e9, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2020.08.051. (https://www.sciencedirect.com/science/article/pii/S0092867420311399)
5. Benn CS, Martins CL, Andersen A, Fisker AB, Whittle HC, Aaby P. Measles Vaccination in Presence of Measles Antibody May Enhance Child Survival. Front Pediatr. 2020 Feb 7; 8:20. doi: 10.3389/fped.2020.00020. PMID: 32117827; PMCID: PMC7020693.
6. Sørup S, Stensballe LG, Krause TG, Aaby P, Benn CS, Ravn H. Oral Polio Vaccination and Hospital Admissions With Non-Polio Infections in Denmark: Nationwide Retrospective Cohort Study. Open Forum Infect Dis. 2015 Dec 17;3(1):ofv204. doi: 10.1093/ofid/ofv204. PMID: 26885538; PMCID: PMC4751340.
7. P. Aaby, C.S. Benn, Developing the concept of beneficial non-specific effect of live vaccines with epidemiological studies, Clinical Microbiology and Infection, Volume 25, Issue 12, 2019, Pages 1459-1467, ISSN 1198-743X, https://doi.org/10.1016/j.cmi.2019.08.011. (https://www.sciencedirect.com/science/article/pii/S1198743X19304525)
8. Leentjens J, Kox M, Stokman R, Gerretsen J, Diavatopoulos DA, van Crevel R, et al. BCG Vaccination Enhances the Immunogenicity of Subsequent Influenza Vaccination in Healthy Volunteers: A Randomized, Placebo-Controlled Pilot Study. J Infect Dis. 2015 Dec 15;212(12):1930-8. doi: 10.1093/infdis/jiv332. Epub 2015 Jun 12. PMID: 26071565.
9. Gonzalez-Perez M, Sanchez-Tarjuelo R, Shor B, Nistal-Villan E, Ochando J. The BCG Vaccine for COVID-19: First Verdict and Future Directions. Front Immunol. 2021 Mar 8;12:632478. doi: 10.3389/fimmu.2021.632478. PMID: 33763077; PMCID: PMC7982405.
10. Laure F. Pittet et al. Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial, e Clinical Medicine Volume 72, 2024, 102616, ISSN 2589-5370, https://doi.org/10.1016/j.eclinm.2024.1-2615.102616. (https://www.sciencedirect.com/science/article/pii/S258953702401950) https://www.mcri.edu.au/research/projects/brace
11. Chimoyi L, Velen K, Churchyard GJ, Wallis R, Lewis JJ, Charalambous S. An ecological study to evaluate the association of Bacillus Calmette-Guerin (BCG) vaccination on cases of SARS-CoV2 infection and mortality from COVID-19. PLoS One. 2020 Dec 17;15(12):e0243707. doi: 10.1371/journa l.pone.0243707. PMID: 33332418; PMCID: PMC77 46266.
12. Noble CCA, Messina NL, Pittet LF, Curtis N. Interpreting the Results of Trials of BCG Vaccination for Protection Against COVID-19. J Infect Dis. 2023 Nov 11;228(10):1467-1478. doi: 10.1093/infdis/jiad316. PMID: 37558650; PMCID: PMC10640778.
13. Specht, A. G., Ginese, M., Kurtz, S. L., Elkins, K. L., et al. (2024). Host Genetic Background Influences BCG-Induced Antibodies Cross-Reactive to SARS-CoV-2 Spike Protein. Vaccines (Basel), 12(3), 242-. https://doi.org/10.3390/vaccines12030242
14. Pittet, L. F., Noble, C. C. A., Messina, N. L., & Curtis, N. (2024). Using BCG vaccination to protect against COVID-19: when reality fails to meet expectation. Nature Reviews. Immunology, 24(2), 83–84. https://doi.org/10.1038/s41577- 024-00992-z
15. Tsilika M, Taks E, Dolianitis K, Kotsaki A, Leventogiannis K, Damoulari C, et al. ACTIVATE-2: A Double-Blind Randomized Trial of BCG Vaccination Against COVID-19 in Individuals at Risk. Front Immunol. 2022 Jul 5; 13:873067. doi: 10.3389/fimmu.2022.873067. Erratum in: Front Immunol. 2022 Aug 31; 13:1018384. doi: 10.3389/fimmu.2022.1018384. PMID: 35865520; PMCID: PMC9294453.
16. Government of India Ministry of Health & Family Welfare Directorate General of Health Services (EMR Division) Revised Guidelines on Clinical Management of COVID – 19, 31 March, 2020 (ICMR)