{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:08:04Z","timestamp":1784214484974,"version":"3.55.0"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007607","name":"University Research Council, Aga Khan University","doi-asserted-by":"publisher","award":["Seed Money grant 80092"],"award-info":[{"award-number":["Seed Money grant 80092"]}],"id":[{"id":"10.13039\/100007607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pakistan is endemic to a diverse set of parasitic, mycobacterial and viral diseases. The recognition of BCG Trained Immunity (TI) led us to postulate that the continued presence of BCG-TI may play a protective role, previously reported for both infectious and noninfectious conditions. Most of the previous studies have addressed the issue of BCG-TI in the paediatric populations. This study addressed the key issue of maintenance of BCG-TI in a wider age range (adolescent and adults) to identify the strength and quality of the immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the BCG-induced recall responses in healthy individuals by cytokines secreted from the TI network and its potential role in providing cross-protection against COVID-19 and other viral infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>In this cross-sectional study, healthy young adults and adolescents (n = 20) were recruited from 16\u201340 years of age, with no prior history of TB treatment, autoimmune, or chronic inflammatory condition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BCG-induced cytokine responses were assessed using prototypic markers for cells of the TI network [macrophages [M1 (TNF\u03b1, IFN\u03b3), M2 (IL10)], NK (IL2), Gamma delta (\u03b3\u03b4) T (IL17, IL4)] and SARS CoV2 IgG antibodies against RBD using short-term (12 hrs.) cultures assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant differences were observed in the magnitude of recall responses to BCG with macrophage cytokines showing the highest mean levels of TNF\u03b1 (9148 pg\/ml) followed by IL10 (488 pg\/ml) and IFN\u03b3 (355 pg\/ml). The ratio of unstimulated vs.BCG-stimulated cytokines was 132 fold higher for TNF\u03b1, 40 fold fo r IL10, and 27 fold for IFN\u03b3. Furthermore, SARS-CoV-2 antibodies were also detected in unstimulated plasma which showed cross reactivity with BCG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec006\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The presence of cross reactive antibodies to SARS-CoV-2 and the relative ratio of pro- and anti-inflammatory cytokines secreted by activated TI cellular network may play a pivotal role in protection in the early stages of infection as observed during the COVID-19 pandemic in the younger age groups resulting in lower morbidity and mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0302722","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T13:22:39Z","timestamp":1715260959000},"page":"e0302722","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["BCG activation of trained immunity is associated with induction of cross reactive COVID-19 antibodies in a BCG vaccinated population"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-5655","authenticated-orcid":true,"given":"Najeeha Talat","family":"Iqbal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumail","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tehniat","family":"Sattar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabia","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"pone.0302722.ref001","unstructured":"WHO. 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