{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:47:10Z","timestamp":1783057630097,"version":"3.54.6"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The Bacillus Calmette\u2013Gu\u00e9rin (BCG) is a well-known vaccine with almost a century of use, with the apparent capability to improve cytokine production and epigenetics changes that could develop a better response to pathogens. It has been postulated that BCG protection against SARS-CoV-2 has a potential role in the pandemic, through the presence of homologous amino acid sequences. To identify a possible link between BCG vaccination coverage and COVID-19 cases, we used official epidemic data and Ecuadorian Ministry of Health and Pan American Health Organization vaccination information. BCG information before 1979 was available only at a national level. Therefore, projections based on the last 20 years were performed, to compare by specific geographic units. We used a Mann\u2013Kendall test to identify BCG coverage variations, and mapping was conducted with a free geographic information system (QGIS). Nine provinces where BCG vaccine coverage was lower than 74.25% show a significant statistical association (\u03c72 Pearson\u2019s = 4.800, df = 1, p = 0.028), with a higher prevalence of cases for people aged 50 to 64 years than in younger people aged 20 to 49 years. Despite the availability of BCG vaccination data and the mathematical models needed to compare these data with COVID-19 cases, our results show that, in geographic areas where BCG coverage was low, 50% presented a high prevalence of COVID-19 cases that were young; thus, low-coverage years were more affected.<\/jats:p>","DOI":"10.3390\/vaccines9020091","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T06:10:54Z","timestamp":1611727854000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["COVID-19 Infection and Previous BCG Vaccination Coverage in the Ecuadorian Population"],"prefix":"10.3390","volume":"9","author":[{"given":"Daniel","family":"Garzon-Chavez","sequence":"first","affiliation":[{"name":"Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Quito CP 170901, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackson","family":"Rivas-Condo","sequence":"additional","affiliation":[{"name":"Ministerio de Salud Publica del Ecuador, Quito CP 170146, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Echeverria","sequence":"additional","affiliation":[{"name":"Ministerio de Salud Publica del Ecuador, Quito CP 170146, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhoanna","family":"Mozo","sequence":"additional","affiliation":[{"name":"Ministerio de Salud Publica del Ecuador, Quito CP 170146, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5600-2361","authenticated-orcid":false,"given":"Emmanuelle","family":"Quentin","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Salud P\u00fablica y Epidemiolog\u00eda Cl\u00ednica, Universidad Tecnol\u00f3gica Equinoccial, Quito CP 170527, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5215-164X","authenticated-orcid":false,"given":"Jorge","family":"Reyes","sequence":"additional","affiliation":[{"name":"Servicio de Laboratorio, Hospital IESS Quito Sur, Quito CP 170111, Ecuador"},{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Central del Ecuador, Quito CP 170403, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-5655","authenticated-orcid":false,"given":"Enrique","family":"Teran","sequence":"additional","affiliation":[{"name":"Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Quito CP 170901, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.jiph.2020.03.019","article-title":"Coronavirus disease 2019 (COVID-19): A literature review","volume":"13","author":"Harapan","year":"2020","journal-title":"J. Infect. Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.dsx.2020.04.020","article-title":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response","volume":"14","year":"2020","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_4","unstructured":"(2020, December 18). Johns Hopkins University Coronavirus COVID-19 Global Cases by Johns Hopkins CSSE. Available online: https:\/\/agers.es\/coronavirus-covid-19-global-cases-by-johns-hopkins-csse\/."},{"key":"ref_5","unstructured":"World Health Organization (2020). Modes of Transmission of Virus Causing COVID-19: Implications for IPC Precaution Recommendations: Scientific brief, 29 March 2020, World Health Organization."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nicolalde, B., A\u00f1azco, D., Mushtaq, M., Aguilar, A., and Ter\u00e1n, E. (2020). Current Pharmacological Therapy against COVID-19: A Latin American Perspective. Clin. Sci. Med. Technol., 59\u201368.","DOI":"10.34141\/LJCS2640133"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103443","DOI":"10.1016\/j.resp.2020.103443","article-title":"Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude?","volume":"277","year":"2020","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gupta, A., Banerjee, S., and Das, S. (2020). Significance of geographical factors to the COVID-19 outbreak in India. Model. Earth Syst. Environ.","DOI":"10.1007\/s40808-020-00838-2"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9696","DOI":"10.1073\/pnas.2004911117","article-title":"Demographic science aids in understanding the spread and fatality rates of COVID-19","volume":"117","author":"Dowd","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","first-page":"1","article-title":"Covid-19 and community mitigation strategies in a pandemic","volume":"368","author":"Ebrahim","year":"2020","journal-title":"BMJ"},{"key":"ref_11","unstructured":"(2020, August 18). Registro Civil Ecuador Cifras Mortalidad 2020 (Mortality 2020). Available online: https:\/\/www.registrocivil.gob.ec\/cifras\/."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Klinger, D., Blass, I., Rappoport, N., and Linial, M. (2020). Significantly improved COVID-19 outcomes in countries with higher bcg vaccination coverage: A multivariable analysis. Vaccines, 8.","DOI":"10.1101\/2020.04.23.20077123"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1001\/jama.2020.8189","article-title":"SARS-CoV-2 Rates in BCG-Vaccinated and Unvaccinated Young Adults","volume":"323","author":"Hamiel","year":"2020","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1093\/clinids\/20.1.126","article-title":"Relationship between Bacille Calmette-Guerin (BCG) Strains and the Efficacy of BCG Vaccine in the Prevention of Tuberculosis","volume":"20","author":"Brewer","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Toraih, E.A., Sedhom, J.A., Dokunmu, T.M., Hussein, M.H., Ruiz, E.M.L., Muthusamy, K., Zerfaoui, M., and Hidden, E.K. (2020). The effects of BCG vaccination in COVID- 19 pandemic. J. Med. Virol.","DOI":"10.1101\/2020.06.09.142760"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.chom.2017.12.010","article-title":"BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity","volume":"23","author":"Arts","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.stem.2020.01.017","article-title":"C\/EBP\u03b2-Dependent Epigenetic Memory Induces Trained Immunity in Hematopoietic Stem Cells","volume":"26","author":"Maurizio","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.1021\/acs.jproteome.0c00410","article-title":"Biological Rationale for the Repurposing of BCG Vaccine against SARS-CoV-2","volume":"19","author":"Glisic","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3233\/BLC-160053","article-title":"Summary and recommendations from the national cancer institute\u2019s clinical trials planning meeting on novel therapeutics for non-muscle invasive bladder cancer","volume":"2","author":"Lerner","year":"2016","journal-title":"Bladder Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/s41585-018-0055-4","article-title":"Mechanisms of BCG immunotherapy and its outlook for bladder cancer","volume":"15","author":"Pettenati","year":"2018","journal-title":"Nat. Rev. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0140-6736(06)68384-0","article-title":"Global epidemiology of tuberculosis","volume":"367","author":"Glaziou","year":"2006","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/lam.13365","article-title":"BCG vaccination early in life does not improve COVID-19 outcome of elderly populations, based on nationally reported data","volume":"71","author":"Wassenaar","year":"2020","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_24","unstructured":"(2020, August 29). Ministerio de Salud P\u00fablica del Ecuador Esquema Nacional de Vacunaci\u00f3n-Ecuador. Available online: https:\/\/www.salud.gob.ec\/wp-content\/uploads\/2020\/01\/ESQUEMA-DE-VACUNACI\u00d3N.DIC_.2019.ok_.pdf%0Ahttps:\/\/www.salud.gob.ec."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sharma, A.R., Batra, G., Kumar, M., Mishra, A., Singla, R., Singh, A., Singh, R.S., and Medhi, B. (2020). BCG as a game-changer to prevent the infection and severity of COVID-19 pandemic?. Allergol. Immunopathol.","DOI":"10.1016\/j.aller.2020.05.002"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1056\/NEJMcibr2011679","article-title":"Trained Innate Immunity, Epigenetics, and Covid-19","volume":"383","author":"Mantovani","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nuovo, G., Tili, E., Suster, D., Matys, E., Hupp, L., and Magro, C. (2020). Strong homology between SARS-CoV-2 envelope protein and a Mycobacterium sp. antigen allows rapid diagnosis of Mycobacterial infections and may provide specific anti-SARS-CoV-2 immunity via the BCG vaccine. Ann. Diagn. Pathol., 48.","DOI":"10.1016\/j.anndiagpath.2020.151600"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/jci.insight.130540","article-title":"BCG revaccination boosts adaptive polyfunctional Th1\/Th17 and innate effectors in IGRA+ and IGRA\u2212 Indian adults","volume":"4","author":"Rakshit","year":"2019","journal-title":"JCI Insight"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.4049\/jimmunol.1501996","article-title":"BCG Re-vaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-lived BCG-Reactive Natural Killer Cell Responses","volume":"197","author":"Suliman","year":"2016","journal-title":"J. Immunol."},{"key":"ref_30","first-page":"150","article-title":"Potential role of Bacillus Calmette-Gu\u00e9rin (BCG) vaccination in COVID-19 pandemic mortality: Epidemiological and Immunological aspects","volume":"38","author":"Charoenlap","year":"2020","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_31","unstructured":"Ahmad, N.A., Akmal, H., Hamid, A., Sahril, N., Fadhli, M., Yusoff, M., Naidu, B.M., and Aris, T. (2017). Bacille Calmette-Guerin (BCG) Revaccination: Is it Beneficial for. Open Access Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17720","DOI":"10.1073\/pnas.2008410117","article-title":"BCG vaccine protection from severe coronavirus disease 2019 (COVID-19)","volume":"117","author":"Escobar","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","first-page":"1569","article-title":"DOTS strategy and community participation: An experience","volume":"13","author":"Molina","year":"2009","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Urashima, M., Otani, K., Hasegawa, Y., and Akutsu, T. (2020). Bcg vaccination and mortality of covid-19 across 173 countries: An ecological study. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17155589"},{"key":"ref_35","first-page":"3","article-title":"Bacillus Calmette-Gu\u00e9rin vaccination and clinical characteristics and outcomes of COVID-19 in Rhode Island, United States: A cohort study","volume":"1","author":"Weng","year":"2020","journal-title":"Epidemiol. Infect."},{"key":"ref_36","first-page":"1","article-title":"Trained immunity: A program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2017","journal-title":"Science"},{"key":"ref_37","first-page":"207","article-title":"Stop playing with data: There is no sound evidence that bacille calmette-gu\u00e9rin may avoid SARS-CoV-2 infection for now","volume":"91","author":"Gualerzi","year":"2020","journal-title":"Acta Biomed."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5470","DOI":"10.1016\/j.vaccine.2015.07.103","article-title":"Management and outcome of Bacille Calmette-Gu\u00e9rin vaccine adverse reactions","volume":"33","author":"Venkataraman","year":"2015","journal-title":"Vaccine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"787","DOI":"10.3899\/jrheum.200395","article-title":"Possible consequences of a shortage of hydroxychloroquine for patients with systemic lupus erythematosus amid the COVID-19 pandemic","volume":"47","author":"Peschken","year":"2020","journal-title":"J. Rheumatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/0-387-25342-4_8","article-title":"Global Market Update BCG vaccine","volume":"568","author":"Teo","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.euf.2018.06.018","article-title":"Manufacturing and the Market: Rationalizing the Shortage of Bacillus Calmette-Gu\u00e9rin","volume":"4","author":"Bandari","year":"2018","journal-title":"Eur. Urol. Focus"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hu, L., Chen, S., Fu, Y., Gao, Z., Long, H., Wang, J.-M., Ren, H.-W., Zuo, Y., Li, H., and Wang, J. (2020). Accepted Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Hospitalized Patients in Wuhan, China. Clin. Infect. Dis., 3.","DOI":"10.1093\/cid\/ciaa539"},{"key":"ref_43","unstructured":"(2020, August 17). Ministry of Finances Presupuesto General del Estado. Available online: https:\/\/www.finanzas.gob.ec\/wp-content\/uploads\/downloads\/2019\/01\/Justificativo-y-Gastos-Proforma-2019-10-dic.pdf%0Ahttps:\/\/www.google.com\/url?sa=t&rct=j&q=&esrc=s&source=web&cd=4&ved=2ahUKEwipmun5iZbpAhWQdd8KHV0CAdwQFjADegQIBBAB&url=https%3A%2F%2Fwww.fina."},{"key":"ref_44","unstructured":"Lopez, E. (2018). Venezuelan Refugees: The Ecuador\/Colombia Border, U.S. Committee for Refugees and Immigrants."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/2\/91\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:15:50Z","timestamp":1760159750000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/2\/91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,27]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["vaccines9020091"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9020091","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,27]]}}}