Stop playing with data: there is no sound evidence that Bacille Calmette-Guérin may avoid SARS-CoV-2 infection (for now).
Main Article Content
Keywords
BCG Vaccine, COVID-19, Correlation of Data, Incidence, Mortality, Tuberculosis
Abstract
Since the beginning of the COVID-19 epidemic, a possible explanation for the high heterogeneity of infection/mortality rates across involved countries was hinted in the prevalence of tuberculosis vaccination with Bacille Calmette-Guérin (BCG). A systematic review was therefore performed on May 2, 2020. A total of 13 articles were ultimately retrieved, 12 of them as preprint papers. All articles were ecological studies of low quality. Most of them did not include main confounding factors (i.e. demographic of the assessed countries, share of peo- ple residing in urban settings, etc.), and simply assessed the differences among incidence/mortality of COVID-19 with vaccination rates or by having vs. having not any vaccination policy for BCG. Even though all studies shared the very same information sources (i.e. international registries for BCG vaccination rates and open source data for COVID-19 epidemics), results were conflicting, with later studies apparently denying any true correlation between COVID-19 occurrence and BCG vaccination rates and/or policies. As a consequence, there is no sound evidence to recommend BCG vaccination for the prevention of COVID-19.
Downloads
References
2. Odone A, Riccò M, Morandi M, Borrini BM, Pasquarella C, Signorelli C. Epidemiology of tuberculosis in a low-incidence Italian region with high immigration rates: Differences between not Italy-born and Italy-born TB cases. BMC Public Health 2011;11:376. https://doi.org/10.1186/1471-2458-11-376.
3. Moorlag SJCFM, Arts RJW, van Crevel R, Netea MG. Non-specific effects of BCG vaccine on viral infections. Clin Microbiol Infect. 2019;25(12):1473–8. https://doi.org/ 10.1016/j.cmi.2019.04.020
4. Hegarty PK, Sfakianos JP, Giannarini G, Dinardo AR. COVID-19 and Bacillus Calmette-Guérin. Eur Urol Oncol. 2020; S2588-9311(20)30049-3. https://doi.org/10.1016/j.euo.2020.04.001.
5. Wardhana, Datau EA, Sultana A, Mandang V V., Jim E. The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly. Acta Med Indones. 2011;43(3):185–90.
6. Stensballe LG, Nante E, Jensen IP, Kofoed PE, Poulsen A, Jensen H, et al. Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: A beneficial effect of BCG vaccination for girls: Community based case-control study. Vaccine. 2005;23(10):1251–7. https://doi.org/ 10.1016/j.vaccine.2004.09.006
7. 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;212(12):1930–8. https://doi.org/ doi: 10.1093/infdis/jiv332
8. Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/ doi: 10.1371/journal.pmed.1000097
9. Akiyama Y, Ishida T. Relationship between COVID-19 death toll doubling time and national BCG vaccination policy. medRxiv 2020;2020.04.06.20055251. Available from: https://www.medrxiv.org/content/10.1101/2020.04.06.20055251v1 https://doi.org/10.1101/2020.04.06.20055251v1
10. Dolgikh S. Further Evidence of a Possible Correlation Between the Severity of Covid-19 and BCG Immunization. medRxiv. 2020;2020.04.07.20056994. Available from: https://www.medrxiv.org/content/10.1101/2020.04.07.20056994v1 https://doi.org/10.1101/2020.04.07.20056994v1
11. Green CM, Dominguez-andres J, Fok ET, Moorlag SJCFM, Negishi Y, Joosten LAB, et al. COVID-19: A model correlating BCG vaccination to protection from mortality implicates trained immunity. medRxiv 2020;2020.04.10.20060905. Available from: www.medrixiv.com/content/10.1101/2020.04.10.20060905v1 https://doi.org/10.1101/2020.04.10.20060905v1
12. Dayal D, Gupta S. Connecting BCG Vaccination and COVID-19: Additional Data. medRxiv. 2020;2755657(M):2020.04.07.20053272. Available from: www.medrixiv.com/content/10.1101/2020.04.07.20053272v1 https://doi.org/10.1101/2020.04.07.20053272v1
13. Sala G, Miyakawa T. Association of BCG vaccination policy with prevalence and mortality of COVID-19. medRxiv 2020;2020.03.30.20048165. Available from: https://www.medrxiv.org/content/10.1101/2020.03.30.20048165. https://doi.org/10.1101/2020.03.30.20048165
14. Shet A, Ray D, Malavige N, Santosham M, Bar-Zeev N. Differential COVID-19-attributable mortality and BCG vaccine use in countries. medRxiv 2020;2020.04.01.20049478. Available from: https://www.medrxiv.org/content/10.1101/2020.04.01.20049478v1 https://doi.org/10.1101/2020.04.01.20049478
15. Klinger D, Blass I, Rappoport N, Linial M. Significantly Improved COVID-19 Outcomes in Countries with Higher BCG Vaccination Coverage : A Multivariable Analysis. medRxiv. 2020;2020.04.23.20077123. Available from: https://www.medrxiv.org/content/10.1101/2020.04.23.20077123 https://doi.org/10.1101/2020.04.23.20077123
16. Berg MK, Yu Q, Salvador CE, Melani I, Kitayama S. Mandated Bacillus Calmette-Guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19. medRxiv. 2020;2020.04.05.20054163. Available from: https://www.medrxiv.org/content/10.1101/2020.04.05.20054163 https://doi.org/10.1101/2020.04.05.20054163
17. Shivendu S, Chakraborty S, Onuchowska A, Srivastava A, Patidar A. Is there evidence that BCG vaccination has non-specific protective effects for COVID 19 infections or is it an illusion created by lack of testing? medRxiv. 2020;2020.04.18.20071142. Available from: https://www.medrxiv.org/content/10.1101/2020.04.18.20071142 https://doi.org/10.1101/2020.04.18.20071142
18. Miller A, Raendelar MJ, Fasciglione K, Roumenova V, Li Y, Otazu GH. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. medRxiv 2020;2020.03.24.20042937. Available from: https://www.medrxiv.org/content/10.1101/2020.03.24.20042937v1 https://doi.org/10.1101/2020.03.24.20042937
19. Singh S. Bcg Vaccines May Not Reduce Covid-19 Mortality Rates. medRxiv 2020;2020.04.11.20062232. Available from: http://medrxiv.org/content/early/2020/04/17/2020.04.11.20062232 https://doi.org/10.1101/2020.04.11.20062232
20. Goswami RP, Mittal D, Goswami RP. Interaction between malarial transmission and BCG vaccination with COVID-19 incidence in the world map: A cross-sectional study. medRxiv 2020;2020.04.03.20052563 Available from: https://www.medrxiv.org/content/10.1101/2020.04.03.20052563 https://doi.org/2020;2020.04.03.20052563
21. Bonanni P, Ferrero A, Guerra R, Iannazzo S, Odone A, Pompa M, et al. Vaccine coverage in Italy and assessment of the 2012-2014 National Immunization Prevention Plan. Epidemiol Prev. 2015;39(4S1):146–158.
22. Signorelli C, Scognamiglio T, Odone A. COVID-19 in Italy: impact of containment measures and prevalence estimates of infection in the general population. Acta Biomed 2020;91(3-S):175–9. doi: 10.23750/abm.v91i3-S.9511
23. Chirico F, Nucera G, Magnavita N. COVID-19: Protecting Healthcare Workers Is a Priority. Infect Control Hosp Epidemiol 2020;epub ahead of print doi: https://doi.org/10.1017/ice.2020.148
24. Ferioli M, Cisternino C, Leo V, Pisani L, Palange P, Nava S. Protecting Healthcare Workers From SARS-CoV-2 Infection: Practical Indications. Eur Respir Rev 2020;29(155):200068. https://doi.org/10.1183/16000617.0068-2020.
25. Riccò M, Ferraro P, Gualerzi G et al. Point-of-Care diagnostic of SARS-CoV-2: knowledge, attitudes, and perceptions (KAP) of medical workforce in Italy. Acta Biomed 2020;91:epub ahead of print https://doi.org/10.23750/abm.v91i2.9573
26. Signorelli C, Odone A, Gianfredi V, et al. The spread of COVID-19 in six western metropolitan regions: a false myth on the excess of mortality in Lombardy and the defense of the city of Milan. Acta Biomed 2020;91:epub ahead of print https://doi.org/10.23750/abm.v91i2.9579
27. Baud D, Qi X, Nielsen-Saines K, et al. Real Estimates of Mortality Following COVID-19 Infection. Lancet Infect Dis 2020;S1473-3099(20)30195-X. https://doi.org/10.1016/S1473-3099(20)30195-X.
28. Guzzetta G, Poletti P, Ajelli M, et al. Potential Short-Term Outcome of an Uncontrolled COVID-19 Epidemic in Lombardy, Italy, February to March Euro Surveill 2020;25(12):2000293. https://doi.org/10.2807/1560-7917.ES.2020.25.12.2000293.
29. Floyd K , Glaziou P, Zumla A et al. The Global Tuberculosis Epidemic and Progress in Care, Prevention, and Research: An Overview in Year 3 of the End TB Era. Lancet Respir Med 2018;6(4):299-314. https://doi.org/10.1016/S2213-2600(18)30057-2
30. Coronavirus (COVID-19) confirmed cases in Russia as of May 3, 2020, by region https://www.statista.com/statistics/1102935/coronavirus-cases-by-region-in-russia/ (accessed on May 4, 2020)