{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:27:06Z","timestamp":1778632026477,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The Bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccine may confer cross\u2010protection against viral diseases in adults. This study evaluated BCG vaccine cross\u2010protection in adults with convalescent coronavirus disease 2019 (COVID\u201019).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This was a multicenter, prospective, randomized, placebo\u2010controlled, double\u2010blind phase III study (ClinicalTrials.gov: NCT04369794). Setting: University Community Health Center and Municipal Outpatient Center in South America. Patients: a total of 378 adult patients with convalescent COVID\u201019 were included. Intervention: single intradermal BCG vaccine (<jats:italic>n<\/jats:italic> = 183) and placebo (<jats:italic>n<\/jats:italic> = 195). Measurements: the primary outcome was clinical evolution. Other outcomes included adverse events and humoral immune responses for up to 6 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significantly higher proportion of BCG patients with anosmia and ageusia recovered at the 6\u2010week follow\u2010up visit than placebo (anosmia: 83.1% vs. 68.7% healed, <jats:italic>p<\/jats:italic> = 0.043, number needed to treat [NNT] = 6.9; ageusia: 81.2% vs. 63.4% healed, <jats:italic>p<\/jats:italic> = 0.032, NNT = 5.6). BCG also prevented the appearance of ageusia in the following weeks: seven in 113 (6.2%) BCG recipients versus 19 in 126 (15.1%) placebos, <jats:italic>p<\/jats:italic> = 0.036, NNT = 11.2. BCG did not induce any severe or systemic adverse effects. The most common and expected adverse effects were local vaccine lesions, erythema (<jats:italic>n<\/jats:italic> = 152; 86.4%), and papules (<jats:italic>n<\/jats:italic> = 111; 63.1%). Anti\u2013severe acute respiratory syndrome coronavirus 2 humoral response measured by N protein immunoglobulin G titer and seroneutralization by interacting with the angiotensin\u2010converting enzyme 2 receptor suggest that the serum of BCG\u2010injected patients may neutralize the virus at lower specificity; however, the results were not statistically significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BCG vaccine is safe and offers cross\u2010protection against COVID\u201019 with potential humoral response modulation. Limitations: No severely ill patients were included.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13523","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T01:53:11Z","timestamp":1653270791000},"page":"654-666","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Randomized clinical trial of BCG vaccine in patients with convalescent COVID\u201019: Clinical evolution, adverse events, and humoral immune response"],"prefix":"10.1111","volume":"292","author":[{"given":"Mehrsa","family":"Jalalizadeh","sequence":"first","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keini","family":"Buosi","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franciele A. V.","family":"Dionato","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana S. B.","family":"Dal Col","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiane F.","family":"Giacomelli","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Carolina","family":"Pagliarone","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia A. F.","family":"Leme","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiane L.","family":"Maia","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Yadollahvandmiandoab","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quoc\u2010Dien","family":"Trinh","sequence":"additional","affiliation":[{"name":"Brigham and Women's Center for Surgery and Public Health Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kleber G.","family":"Franchini","sequence":"additional","affiliation":[{"name":"Brazilian Center for Research in Energy and Materials CNPEM Brazilian Biosciences National Laboratory\u2014LNBio  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcio C.","family":"Bajgelman","sequence":"additional","affiliation":[{"name":"Brazilian Center for Research in Energy and Materials CNPEM Brazilian Biosciences National Laboratory\u2014LNBio  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2092-414X","authenticated-orcid":false,"given":"Leonardo O.","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of UroScience School of Medical Sciences State University of Campinas\u2014UNICAMP  Campinas Brazil"},{"name":"Center for Life Sciences Pontifical Catholic University of Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"World Health Organization.WHO World Health Organization global tuberculosis program. 20 November 2021.www.acpjournals.org\/doi\/pdf\/10.7326\/M21\u20103507(2021). Accessed 20 Nov 2021."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-018-0055-4"},{"key":"e_1_2_12_4_1","unstructured":"Minist\u00e9rio da Saud\u00e9.Calend\u00e1rio Nacional de Vacina\u00e7\u00e3o.https:\/\/www.gov.br\/saude\/pt\u2010br\/assuntos\/saude\u2010de\u2010a\u2010a\u2010z\/c\/calendario\u2010nacional\u2010de\u2010vacinacao(2021). Accessed 20 Nov 2021."},{"key":"e_1_2_12_5_1","unstructured":"PauloPS.Nota t\u00e9cnica Cidade de S\u00e3o Paulo: Vacina\u00e7\u00e3o com a vacina BCG: indica\u00e7\u00f5es contraindica\u00e7\u00f5es eventos adversos e condutas. 19 November 2020.https:\/\/www.prefeitura.sp.gov.br\/cidade\/secretarias\/upload\/saude\/nota_tecnica_10_2020_bcg.pdf(2021). Accessed 20 Nov 2021."},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.08.016"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg7181"},{"key":"e_1_2_12_8_1","unstructured":"Minist\u00e9rio da Saud\u00e9.Manual de vigil\u00e2ncia epidemiol\u00f3gica de eventos adversos p\u00f3s\u2010vacina\u00e7\u00e3o.https:\/\/bvsms.saude.gov.br\/bvs\/publicacoes\/manual_vigilancia_epidemiologica_eventos_vacinacao_4ed.pdf(2020). Accessed 20 Nov 2021."},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.777212"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0337-y"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv332"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14345"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-87731-9"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2021.1956228"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI145157"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m3731"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2507"},{"key":"e_1_2_12_18_1","first-page":"1","article-title":"Understanding neutralizing antibodies against SARS\u2010CoV\u20102 and their implications in clinical practice","volume":"8","author":"Pang NY","year":"2021","journal-title":"Mil Med Res."},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01948-2020"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2020.102581"},{"key":"e_1_2_12_21_1","first-page":"1","article-title":"Cross\u2010reactivity of antibodies from non\u2010hospitalized COVID\u201019 positive individuals against the native, B. 1.351, B. 1.617. 2, and P. 1 SARS\u2010CoV\u20102 spike proteins","volume":"11","author":"Jodaylami MH","year":"2021","journal-title":"Sci Rep."},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.632478"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.03.013"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02806"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.12.010"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv332"},{"key":"e_1_2_12_27_1","unstructured":"WHO Expert Committee on Biological Standardization.Recommendations to assure the quality safety and efficacy of BCG vaccines. Replacement of Annex 2 of WHO Technical Report Series No. 745 and Amendment to Annex 12 of WHO Technical Report Series No. 771. Geneva.2013."}],"container-title":["Journal of Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.13523","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/joim.13523","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.13523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T15:34:34Z","timestamp":1692718474000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joim.13523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,3]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/joim.13523"],"URL":"https:\/\/doi.org\/10.1111\/joim.13523","archive":["Portico"],"relation":{},"ISSN":["0954-6820","1365-2796"],"issn-type":[{"value":"0954-6820","type":"print"},{"value":"1365-2796","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,3]]},"assertion":[{"value":"2022-06-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}