{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:22:04Z","timestamp":1777425724794,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EB032983"],"award-info":[{"award-number":["EB032983"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI170774"],"award-info":[{"award-number":["AI170774"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG078268"],"award-info":[{"award-number":["AG078268"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cancer Prevention Institute of Texas","award":["RP210227"],"award-info":[{"award-number":["RP210227"]}]},{"name":"Cancer Prevention Institute of Texas","award":["RP200504"],"award-info":[{"award-number":["RP200504"]}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","award":["P30 ES030285"],"award-info":[{"award-number":["P30 ES030285"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"publisher","award":["P42 ES027725"],"award-info":[{"award-number":["P42 ES027725"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)\u2013related frequency or severity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline). Enrollment included 529 healthcare workers randomized to receive BCG or placebo. Primary analysis evaluated COVID-19 disease frequency, while secondary analysis evaluated coronavirus immunity in a subset of participants. Study enrollment ceased early in December 2020 following introduction of COVID-19\u2013specific vaccines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Study enrollment was halted early, prior to reaching the targeted recruitment, and was not powered to detect a decrease in COVID-19 frequency. Symptomatic COVID-19 occurred in 21 of 263 and 10 of 266 participants in the BCG and placebo arms, respectively (P = .50, Fisher exact test). Participants vaccinated with BCG, but uninfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrated increased coronavirus vaccine immunity (increase spike-inducible levels of tumor necrosis factor, interleukin 6, and interleukin 1\u03b2) 12 months after BCG vaccination compared to participants receiving placebo. Immune responsiveness to SARS-CoV-2 antigens correlated with BCG-induced DNA methylation changes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Due to early study closure, the study was not powered to evaluate COVID-19 frequency. Secondary analysis demonstrated that 12 months following vaccination, BCG increased coronavirus vaccine immunity compared to those who did not receive BCG. This increase in COVID-19 vaccine immunity correlated with BCG-induced DNA methylation changes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofaf007","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T11:03:17Z","timestamp":1737025397000},"source":"Crossref","is-referenced-by-count":3,"title":["BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8731-0105","authenticated-orcid":false,"given":"Santiago","family":"Carrero Longlax","sequence":"first","affiliation":[{"name":"Global Tuberculosis Program, William T. 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