{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:04:01Z","timestamp":1772118241788,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,6,5]],"date-time":"2022-06-05T00:00:00Z","timestamp":1654387200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical and Translational Dis"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Endeavors to identify potentially protective variables for COVID\u201019 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID\u201019 impact on populations to their Bacillus\u2013Calmette\u2013Gu\u00e9rin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID\u201019 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous \u2018trained immunity\u2019 (TI) conferred by exposure to\n                    <jats:italic>Mycobacterium<\/jats:italic>\n                    spp. (i.e., environmental and BCG), it is argued that the estimates of the prevalence of TI in populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (24), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID\u201019 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase\u2010matched COVID\u201019 incidences (\n                    <jats:italic>r<\/jats:italic>\n                    (24): \u22120.79 to \u22120.57;\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value\u00a0&lt;\u00a0.004), mortality (\n                    <jats:italic>r<\/jats:italic>\n                    (24): \u22120.63 to \u22120.45;\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value\u00a0&lt;\u00a0.03), and interim case fatality rates (\n                    <jats:italic>i<\/jats:italic>\n                    \u2010CFR) data. To decisively arrive at dependable conclusions about the potential protective benefit gained from BCG vaccination in COVID\u201019, the ongoing or planned randomized controlled trials should consciously consider including measures of TI as: (a) all individuals immunized do not respond equally, (b) small study groups from higher background TI could fail to indicate any protective effect.\n                  <\/jats:p>","DOI":"10.1002\/ctd2.60","type":"journal-article","created":{"date-parts":[[2022,6,5]],"date-time":"2022-06-05T11:19:20Z","timestamp":1654427960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Higher BCG\u2010induced trained immunity prevalence predicts protection from COVID\u201019: Implications for ongoing BCG trials"],"prefix":"10.1002","volume":"2","author":[{"given":"Samer","family":"Singh","sequence":"first","affiliation":[{"name":"Centre of Experimental Medicine &amp; Surgery Institute of Medical Sciences Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhiraj","family":"Kishore","sequence":"additional","affiliation":[{"name":"Department of General Medicine Institute of Medical Sciences Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Science Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandramani","family":"Pathak","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology Amity University  Gurgaon Haryana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kishu","family":"Ranjan","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Medicine Yale University  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008410117"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc1463"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2016733117"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2015234117"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.14097"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008969"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.1.9801120"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/2020.04.11.20062232"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.8189"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26450"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0337-y"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40520-020-01619-8"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.699389"},{"issue":"2","key":"e_1_2_10_15_1","first-page":"153","article-title":"Covariation of zinc deficiency with COVID19 infections and mortality in European countries: is zinc deficiency a risk factor for COVID\u201019?","volume":"64","author":"Singh S","year":"2020","journal-title":"J Sci Res"},{"key":"e_1_2_10_16_1","unstructured":"ZwerlingA BehrM VermaA BrewerT MenziesD PaiM World atlas of BCG policies and practices 3rd ed.http:\/\/www.bcgatlas.org\/index.php(Accessed on 10 February 2022)"},{"key":"e_1_2_10_17_1","unstructured":"Worldometer.COVID\u201019 Coronavirus pandemic.https:\/\/www.worldometers.info\/coronavirus\/(Accessed on 27\u201030 August 2020)"},{"key":"e_1_2_10_18_1","unstructured":"WHO.Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. 2018.https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/260233\/9789241550239eng.pdf;jsessionid=24D3F1097E3884502A9C1A1698348491?sequence=1 (Accessed on 10 February 2022)"},{"key":"e_1_2_10_19_1","unstructured":"IHME.Global Burden of Disease Collaborative Network. 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