{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:47:26Z","timestamp":1760402846962,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The Bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccine affords indirect protection against COVID-19, which is presumably due to priming of the innate immune system. It was hypothesized that the live attenuated Varicella Zoster (LAVZ) vaccine, recommended for the elderly population, would also protect against COVID-19 infection. A retrospective population-based cross-sectional study was conducted using the Leumit Health Services (LHS) database. LAVZ-vaccinated patients were matched with controls based on a propensity score model using 1:9 nearest-neighbor matching. Matching was based on age, gender, and the presence of some chronic disorders, which were selected according to their association with COVID-19 infection. Multivariate logistic regression analyses, adjusted for sex, age, smoking status, comorbidities, and chronic medications associated with COVID-19 risk, were used to estimate the association between LAVZ vaccination and COVID-19 RT-PCR results. Subjects (625) vaccinated with LAVZ and RT-PCR-tested for COVID-19 were identified. After 1:9 matching of subjects who received the LAVZ vaccine, 6250 subjects were included in the study. Multivariate logistic regression analysis demonstrated a significant and independent negative association between having received the LAVZ vaccine and the likelihood of COVID-19 infection (adjusted OR = 0.47 (95% CI 0.33\u20130.69, p &lt; 0.001)). This association was further strengthened after separate analysis based on the time of LAVZ vaccination before COVID-19 RT-PCR testing. Individuals aged \u226550 years vaccinated with LAVZ had a decreased likelihood of being tested positive for COVID-19.<\/jats:p>","DOI":"10.3390\/vaccines10010074","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T23:35:09Z","timestamp":1641771309000},"page":"74","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Association of Previous Vaccination with Live-Attenuated Varicella Zoster Vaccine and COVID-19 Positivity: An Israeli Population-Based Study"],"prefix":"10.3390","volume":"10","author":[{"given":"Eugene","family":"Merzon","sequence":"first","affiliation":[{"name":"Leumit Health Services, Tel Aviv 6473817, Israel"},{"name":"Adelson School of Medicine, Ariel University, Ariel 4076414, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9435-7152","authenticated-orcid":false,"given":"Ilan","family":"Green","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv 6473817, Israel"},{"name":"Department of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eli","family":"Somekh","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Mayanei Hayeshuah Medical Centre, Bnei Brak 5154475, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo","family":"Vinker","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv 6473817, Israel"},{"name":"Department of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avivit","family":"Golan-Cohen","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv 6473817, Israel"},{"name":"Department of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-8896","authenticated-orcid":false,"given":"Ariel","family":"Israel","sequence":"additional","affiliation":[{"name":"Leumit Health Services, Tel Aviv 6473817, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Gorohovski","sequence":"additional","affiliation":[{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0329-4599","authenticated-orcid":false,"given":"Milana","family":"Frenkel-Morgenstern","sequence":"additional","affiliation":[{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Stein","sequence":"additional","affiliation":[{"name":"Infectious Disease and Infection Control Unit, Hillel Yaffe Medical Center, Hadera 38100, Israel"},{"name":"Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa 3525433, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/S0163-4453(17)30185-8","article-title":"Measles, immune suppression and vaccination: Direct and indirect nonspecific vaccine benefits","volume":"74","author":"Mina","year":"2017","journal-title":"J. Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1126\/science.aaa3662","article-title":"Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality","volume":"348","author":"Mina","year":"2015","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/infdis\/jir240","article-title":"Randomized Trial of BCG Vaccination at Birth to Low-Birth-Weight Children: Beneficial Nonspecific Effects in the Neonatal Period?","volume":"204","author":"Aaby","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1093\/cid\/civ144","article-title":"Nonspecific (heterologous) protection of neonatal BCG vaccination against hospitalization due to respiratory infection and sepsis","volume":"60","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","unstructured":"N\u00e4slund, C. (1932). Resultats des Experiences de Vaccination par le BCG Poursuivies dans le NORRBOTTEN (Su\u00e8de) (Septembre 1927\u2013D\u00e9cembre 1931). Vaccination Preventative de Tuberculose, Rapports et Documents, Institut Pasteur."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.vaccine.2004.09.006","article-title":"Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: A beneficial effect of BCG vaccination for girls: Community based case\u2013control study","volume":"23","author":"Stensballe","year":"2005","journal-title":"Vaccine"},{"key":"ref_7","first-page":"185","article-title":"The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly","volume":"43","author":"Wardhana","year":"2011","journal-title":"Acta Med. Indones."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17720","DOI":"10.1073\/pnas.2008410117","article-title":"BCG vaccine protection from severe coronavirus disease 2019 (COVID-19)","volume":"117","author":"Escobar","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","unstructured":"Murdoch Childrens Research Institute (2021, February 28). BCG Vaccination to Protect Healthcare Workers against COVID-19 (BRACE). Clinicaltrials.gov, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04327206."},{"key":"ref_10","unstructured":"Bonten, M.J.M. (2021, February 28). Reducing Health Care Workers Absenteeism in COVID-19 Pandemic through BCG Vaccine (BCG-CORONA), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04328441."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1080\/21645515.2020.1852010","article-title":"The association of previous influenza vaccination and coronavirus disease-2019","volume":"17","author":"Green","year":"2021","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/ni.3178","article-title":"Innate immune memory: A paradigm shift in understanding host defense","volume":"16","author":"Netea","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"aaf1098","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: A program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1056\/NEJMcibr2011679","article-title":"Trained Innate Immunity, Epigenetics, and COVID-19","volume":"383","author":"Mantovani","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/425037a","article-title":"Innate defence: Evidence for memory in invertebrate immunity","volume":"425","author":"Kurtz","year":"2003","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.stem.2020.03.014","article-title":"C\/EBP\u03b2-Dependent epigenetic memory induces trained immunity in hematopoietic stem cells","volume":"26","author":"Maurizio","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.chom.2020.05.014","article-title":"BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment","volume":"28","author":"Cirovic","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors associated with COVID-19-related death using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature"},{"key":"ref_19","first-page":"1775","article-title":"Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy","volume":"323","author":"Onder","year":"2020","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized with COVID-19 in the New York City Area","volume":"323","author":"Richardson","year":"2020","journal-title":"JAMA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1086\/605611","article-title":"Varicella-Zoster Virus\u2013Specific Immune Responses to Herpes Zoster in Elderly Participants in a Trial of a Clinically Effective Zoster Vaccine","volume":"200","author":"Weinberg","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1086\/528696","article-title":"Varicella-Zoster Virus\u2013Specific Immune Responses in Elderly Recipients of a Herpes Zoster Vaccine","volume":"197","author":"Levin","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_23","first-page":"537","article-title":"Assessment of the completeness and accuracy of computer medical records in four practices committed to recording data on computer","volume":"45","author":"Pringle","year":"1995","journal-title":"Br. J. Gen. Pract."},{"key":"ref_24","first-page":"404","article-title":"Prevalence of selected chronic diseases in Israel","volume":"3","author":"Rennert","year":"2001","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.ijcard.2010.08.002","article-title":"The use of an automated patient registry to manage and monitor cardiovascular conditions and related outcomes in a large health organization","volume":"152","author":"Shalev","year":"2011","journal-title":"Int. J. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1023\/B:EJEP.0000006635.36802.c8","article-title":"The epidemiology of diabetes in a large Israeli HMO","volume":"18","author":"Chodick","year":"2002","journal-title":"Eur. J. Epidemiol."},{"key":"ref_27","unstructured":"World Health Organization (WHO) (2021, December 01). Laboratory Testing for 2019 Novel Coronavirus (2019-nCoV) in Suspected Human Cases. Interim Guidance. Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/331501\/WHO-COVID-19-laboratory-2020."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.3201\/eid2608.200679","article-title":"Population-Based Estimates of Chronic Conditions Affecting Risk for Complications from Coronavirus Disease, United States","volume":"26","author":"Adams","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1177\/1087054720943271","article-title":"ADHD as a Risk Factor for Infection With COVID-19","volume":"25","author":"Merzon","year":"2021","journal-title":"J. Atten. Disord."},{"key":"ref_30","first-page":"e3398","article-title":"Hemoglobin A1C is a Predictor of COVID-19 Severity in Patients with Diabetes","volume":"27","author":"Merzon","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_31","unstructured":"Green, I., Merzon, E., Vinker, S., Golan-Cohen, A., and Magen, E. (2020). Potential protective effect of asthma on COVID-19 susceptibility. J. Allergy Clin. Immunol. Pract., 23, S2213-2198(20)31240-X."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1111\/febs.15784","article-title":"The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection","volume":"288","author":"Merzon","year":"2021","journal-title":"FEBS J."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/1\/74\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:00:05Z","timestamp":1760364005000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/1\/74"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["vaccines10010074"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10010074","relation":{},"ISSN":["2076-393X"],"issn-type":[{"type":"electronic","value":"2076-393X"}],"subject":[],"published":{"date-parts":[[2022,1,4]]}}}