{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T07:32:08Z","timestamp":1776411128555,"version":"3.51.2"},"reference-count":15,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,7,5]],"date-time":"2020-07-05T00:00:00Z","timestamp":1593907200000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003400","name":"Ministry of Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,6,20]]},"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:p>The COVID-19 pandemic has killed over 400 000 people globally. Ecological evidence indicates that countries with national universal BCG vaccination programs for tuberculosis (TB) prevention have a much lower incidence of severe COVID-19 and mortality compared with those that do not have such programs. BCG is a century old vaccine used for TB prevention via infant\/childhood vaccination in lowto middle-income countries with high infection prevalence rate and is known to reduce all-cause neonatal mortality. BCG remains the standard immunotherapy treatment for patients with high-risk non-muscle invasive bladder cancer globally for more than 44 years. Several trials are, therefore, investigating BCG as a prophylactic against COVID-19 in healthcare workers and the elderly. In this commentary, we discuss the potential mechanisms that may underlie BCG associated heterologous protection with a focus on tertiary lymphoid structure (TLS) organogenesis. Given the significance of TLSs in mucosal immunity, their association with positive prognosis and response to immune checkpoint blockade with a critical role of Type I interferon (IFN-1) in inducing these, we also discuss potentiating TLS formation as a promising approach to enhance anti-tumor immunity. We propose that lessons learned from BCG immunotherapy success could be applied to not only augment such microbe-based therapeutics but also lead to similar adjunctive IFN-1 activating approaches to improve response to immune checkpoint blockade therapy in cancer.<\/jats:p>","DOI":"10.1136\/jitc-2020-001119","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T05:59:35Z","timestamp":1594101575000},"page":"e001119","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy"],"prefix":"10.1136","volume":"8","author":[{"given":"Madhuri","family":"Koti","sequence":"first","affiliation":[{"name":"Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada"},{"name":"Department of Urology, Queen's University, Kingston, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Urology, Queen's University, Kingston, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles H","family":"Graham","sequence":"additional","affiliation":[{"name":"Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada"},{"name":"Department of Urology, Queen's University, Kingston, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Robert","family":"Siemens","sequence":"additional","affiliation":[{"name":"Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada"},{"name":"Department of Urology, Queen's University, Kingston, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"2025100312134079000_8.2.e001119.1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-5347(17)58737-6"},{"key":"2025100312134079000_8.2.e001119.2","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aax4517","article-title":"Bcg vaccination\u2013induced emergency granulopoiesis provides rapid protection from neonatal sepsis","volume":"12","author":"Brook","year":"2020","journal-title":"Sci Transl Med"},{"key":"2025100312134079000_8.2.e001119.3","doi-asserted-by":"crossref","unstructured":"Hegarty PK , Sfakianos JP , Giannarini G , et al . COVID-19 and Bacillus Calmette-Gu\u00e9rin: what is the link? 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