{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:02:00Z","timestamp":1779296520000,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Agency","award":["BCG\/COVID-19\/UR\/04\/2020"],"award-info":[{"award-number":["BCG\/COVID-19\/UR\/04\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Tuberculosis vaccines (Bacillus Calmette-Gu\u00e9rin, BCG) were introduced 100 years ago and are still recommended by the World Health Organization to prevent the disease. Studies have shown that BCG vaccination can stimulate non-specific immune responses and reduce the incidence of certain diseases. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, it was hypothesised that the incidence of COVID-19 was lower in countries with BCG prevention. In an attempt to verify this thesis, we conducted a multicenter, randomised, double-blind, placebo-controlled study on a group of 695 health care workers aged 25 years and over in Poland. All participants in the study had a tuberculin test, after which those who were negative were randomised (1:1) and received either the BCG- or placebo vaccine. From then on, these people were subjected to three months of observation for the occurrence of COVID-19 symptoms. The statistical analysis did not reveal any significant correlation between the frequency of incidents suspected of COVID-19 and BCG-10 vaccination, the result of the tuberculin test and the number of scars. The only statistically significant feature was the type of medical profession\u2014nurses became infected more often than doctors or other medical workers (p = 0.02). The results differ from similar trials in other countries. Perhaps this is due to the lack of an unvaccinated control group. The impact of BCG vaccination on the course of COVID-19 requires further research.<\/jats:p>","DOI":"10.3390\/vaccines10020314","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T20:26:41Z","timestamp":1645129601000},"page":"314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["A Multi-Center, Randomised, Double-Blind, Placebo-Controlled Phase III Clinical Trial Evaluating the Impact of BCG Re-Vaccination on the Incidence and Severity of SARS-CoV-2 Infections among Symptomatic Healthcare Professionals during the COVID-19 Pandemic in Poland\u2014First Results"],"prefix":"10.3390","volume":"10","author":[{"given":"Hanna","family":"Czajka","sequence":"first","affiliation":[{"name":"College of Medical Sciences, University of Rzesz\u00f3w, 35-315 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9935-472X","authenticated-orcid":false,"given":"Pawe\u0142","family":"Zapolnik","sequence":"additional","affiliation":[{"name":"College of Medical Sciences, University of Rzesz\u00f3w, 35-315 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-8398","authenticated-orcid":false,"given":"\u0141ukasz","family":"Krzych","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Therapy, Faculty of Medical Sciences, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Kmiecik","sequence":"additional","affiliation":[{"name":"St. Louis Provincial Specialist Children\u2019s Hospital, 31-503 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5370-0180","authenticated-orcid":false,"given":"Lidia","family":"Stopyra","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Paediatrics, Stefan \u017beromski Specialist Hospital, 31-913 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5713-518X","authenticated-orcid":false,"given":"Anna","family":"Nowakowska","sequence":"additional","affiliation":[{"name":"Medical Diagnostics Laboratory, Regional Sanitary-Epidemiological Station, College of Medical Sciences, University of Rzesz\u00f3w, 35-315 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-7854","authenticated-orcid":false,"given":"Teresa","family":"Jackowska","sequence":"additional","affiliation":[{"name":"Blessed Jerzy Popie\u0142uszko Bielany Hospital, 01-809 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Darmochwa\u0142-Kolarz","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, St. Queen Jadwiga Regional Teaching Hospital No. 2, College of Medical Sciences, University of Rzesz\u00f3w, 35-315 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henryk","family":"Szyma\u0144ski","sequence":"additional","affiliation":[{"name":"Saint Hedwig of Silesia Hospital, 55-100 Trzebnica, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2478-1326","authenticated-orcid":false,"given":"Igor","family":"Radziewicz-Winnicki","sequence":"additional","affiliation":[{"name":"Transfiguration of the Lord Praga Hospital, 03-401 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5393-3515","authenticated-orcid":false,"given":"Artur","family":"Mazur","sequence":"additional","affiliation":[{"name":"College of Medical Sciences, University of Rzesz\u00f3w, 35-315 Rzesz\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2011). Recommendations to Assure the Quality, Safety and Efficacy of BCG Vaccines, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zwerling, A., Behr, M.A., Verma, A., Brewer, T.F., Menzies, D., and Pai, M. (2011). The BCG World Atlas: A database of global BCG vaccination policies and practices. PLoS Med., 8.","DOI":"10.1371\/journal.pmed.1001012"},{"key":"ref_3","unstructured":"Magdzik, W., Naruszewicz-Lesiuk, D., and Zieli\u0144ski, A. (2007). Wakcynologia, Alfa Medica Press. [2nd ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1016\/S0264-410X(03)00181-6","article-title":"BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?","volume":"21","author":"Garly","year":"2003","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1136\/archdischild-2016-310760","article-title":"BCG vaccination at birth and early childhood hospitalisation: A randomised clinical multicentre trial","volume":"102","author":"Stensballe","year":"2017","journal-title":"Arch. Dis. Child."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/infdis\/jir240","article-title":"Randomized trial of BCG vaccination at birth to low-birth-weight children: Beneficial nonspecific effects in the neonatal period?","volume":"204","author":"Aaby","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"aaf1098","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: A program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1001\/jamapediatrics.2018.4038","article-title":"Safety and Immunogenicity of Early Bacillus Calmette-Gu\u00e9rin Vaccination in Infants Who Are Preterm and\/or Have Low Birth Weights: A Systematic Review and Meta-analysis","volume":"173","author":"Badurdeen","year":"2019","journal-title":"JAMA Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1093\/infdis\/jiv332","article-title":"BCG Vaccination Enhances the Immunogenicity of Subsequent Influenza Vaccination in Healthy Volunteers: A Randomized, Placebo-Controlled Pilot Study","volume":"212","author":"Leentjens","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hensel, J., McAndrews, K.M., McGrail, D.J., Dowlatshahi, D.P., LeBleu, V.S., and Kalluri, R. (2020). Exercising caution in correlating COVID-19 incidence and mortality rates with BCG vaccination policies due to variable rates of SARS CoV-2 testing. medRxiv.","DOI":"10.1101\/2020.04.08.20056051"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"SSRN (2020, April 05). The Correlation between BCG Immunization Coverage and the Severity of COVID-19. Available online: https:\/\/doi.org\/10.2139\/ssrn.3568954.","DOI":"10.2139\/ssrn.3568954"},{"key":"ref_12","unstructured":"ResearchGate (2021, October 03). Association between BCG Policy and COVID19 Infection Rates Is Significantly Confounded by Age and Is Unlikely to Alter Infection or Mortality Rates. Available online: https:\/\/www.researchgate.net\/publication\/340463940."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Shet, A., Ray, D., Malavige, N., Santosham, M., and Bar-Zeev, N. (2020). Differential COVID-19-attributable mortality and BCG vaccine use in countries. medRxiv.","DOI":"10.1101\/2020.04.01.20049478"},{"key":"ref_14","unstructured":"Devi, D., and Saniya Gupta, S. (2020). Connecting BCG Vaccination and COVID-19: Additional Data. medRxiv."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kurthkoti, K., and Das, G. (2021, October 16). Mechanism of heterologous resistance of BCG to COVID-19. Available online: https:\/\/osf.io\/f32pz\/.","DOI":"10.31219\/osf.io\/f32pz"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eabc1463","DOI":"10.1126\/sciadv.abc1463","article-title":"Mandated Bacillus Calmette-Gu\u00e9rin (BCG) vaccination predicts flattened curves for the spread of COVID-19","volume":"6","author":"Berg","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_17","unstructured":"(2021, October 16). ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/results?pg=1&load=cart&id=NCT04347876+OR+NCT04350931+OR+NCT04327206+OR+NCT04328441+OR+NCT04348370."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e140","DOI":"10.1017\/S0950268820001569","article-title":"Bacillus Calmette-Gu\u00e9rin vaccination and clinical characteristics and outcomes of COVID-19 in Rhode Island, United States: A cohort study","volume":"148","author":"Weng","year":"2020","journal-title":"Epidemiol. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e145157","DOI":"10.1172\/JCI145157","article-title":"BCG vaccination history associates with decreased SARS-CoV-2 seroprevalence across a diverse cohort of health care workers","volume":"131","author":"Rivas","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tsilika, M., Taks, E., Dolianitis, K., Kotsaki, A., Leventogiannis, K., Damoulari, C., Kostoula, M., Paneta, M., Adamis, G., and Papanikolaou, I.C. (2021). Activate-2: A Double-Blind Randomized Trial Of Bcg Vaccination Against Covid19 In Individuals At Risk. medRxiv.","DOI":"10.1101\/2021.05.20.21257520"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1080\/21645515.2021.1956228","article-title":"Effectiveness of booster BCG vaccination in preventing COVID-19 infection","volume":"17","author":"Amirlak","year":"2021","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1080\/14760584.2020.1843432","article-title":"COVID-19 in health-care workers: Lessons from SARS and MERS epidemics and perspectives for chemoprophylaxis and vaccines","volume":"19","author":"Labetoulle","year":"2020","journal-title":"Expert Rev. Vaccines"},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/aje\/kwaa191","article-title":"COVID-19 in Health-Care Workers: A Living Systematic Review and Meta-Analysis of Prevalence, Risk Factors, Clinical Characteristics, and Outcomes","volume":"190","author":"Franco","year":"2021","journal-title":"Am. J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17537","DOI":"10.1073\/pnas.1202870109","article-title":"Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes","volume":"109","author":"Kleinnijenhuis","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","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"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/2\/314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:21:28Z","timestamp":1760134888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/2\/314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,17]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["vaccines10020314"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10020314","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,17]]}}}