{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:38:30Z","timestamp":1760146710229,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"E.O. Ospedali Galliera, Genoa, Italy","award":["SPER22","101046016","26037"],"award-info":[{"award-number":["SPER22","101046016","26037"]}]},{"name":"WeCare Association and Lions Club Genova Sant\u2019Agata","award":["SPER22","101046016","26037"],"award-info":[{"award-number":["SPER22","101046016","26037"]}]},{"name":"Italian Ministry of Health","award":["SPER22","101046016","26037"],"award-info":[{"award-number":["SPER22","101046016","26037"]}]},{"name":"European Union\u2019s Horizon Europe research and innovation program","award":["SPER22","101046016","26037"],"award-info":[{"award-number":["SPER22","101046016","26037"]}]},{"name":"AIRC Foundation under the IG 2021 program","award":["SPER22","101046016","26037"],"award-info":[{"award-number":["SPER22","101046016","26037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Our previous study of 291 cancer patients, we showed that 20% did not respond to two doses of COVID-19 vaccine administered six weeks apart. Methods: Here, we investigated if psychological factors (distress, anxiety, and depressive symptoms) affected antibody response and markers of vaccine activation (D-dimer) after 6 months from initial vaccination. Results: Overall, 31 subjects (14.2%) had no antibody response at 6 months. Our analysis revealed significant predictors of vaccine failure, including the stage of metastatic disease and high-stress levels (OR = 2.46, 95% CI, 1.05\u20135.77, p = 0.04). Notably, nonresponders showed twice the prevalence of distress than responders (21% vs. 10%, p = 0.04). Longitudinal measurements of IgG levels indicated that participants with high depressive symptoms at baseline maintained lower antibody levels over six months (p = 0.003). In addition, women with high anxiety showed reduced levels of D-dimer at 6 months (p = 0.03). These data also showed that smokers and former smokers had significantly lower antibody levels than their nonsmoking counterparts (p = 0.0004). At baseline, the high discomfort rate (\u22655) was 34.4% in women and 23.8% in men; only men experienced an increase in median discomfort during the observation period. Moreover, a higher educational level was related to increased distress among women (p = 0.046). Conclusions: These findings underscore a critical association between elevated psychological distress and reduced immune responses to the COVID-19 vaccine, emphasizing the urgent need for targeted psychological and behavioral support within this vulnerable population.<\/jats:p>","DOI":"10.3390\/cancers16234012","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T03:50:57Z","timestamp":1733111457000},"page":"4012","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Distress, Anxiety, and Depressive Symptoms on SARS-CoV-2 mRNA BNT162b2 Vaccine Efficacy in Cancer Patients"],"prefix":"10.3390","volume":"16","author":[{"given":"Gabriella","family":"Rondanina","sequence":"first","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3605-2828","authenticated-orcid":false,"given":"Tania","family":"Buttiron Webber","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oriana","family":"D\u2019Ecclesiis","sequence":"additional","affiliation":[{"name":"European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-7609","authenticated-orcid":false,"given":"Marco","family":"Musso","sequence":"additional","affiliation":[{"name":"IST Nord-Centro Risorse Biologiche, Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-0026","authenticated-orcid":false,"given":"Irene Maria","family":"Briata","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-3852","authenticated-orcid":false,"given":"Nicoletta","family":"Provinciali","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Boitano","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Clavarezza","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5821-3410","authenticated-orcid":false,"given":"Mauro","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlotta","family":"Defferrari","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Gozza","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonello","family":"Innocenti","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9907-3299","authenticated-orcid":false,"given":"Alessio","family":"Carbone","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5913-9258","authenticated-orcid":false,"given":"Martino","family":"Oliva","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-7566","authenticated-orcid":false,"given":"Emanuela","family":"Marcenaro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genoa, 16126 Genova, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Filauro","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-4548","authenticated-orcid":false,"given":"Sara","family":"Gandini","sequence":"additional","affiliation":[{"name":"European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2635-4491","authenticated-orcid":false,"given":"Andrea","family":"DeCensi","sequence":"additional","affiliation":[{"name":"Oncology Department, E.O. Ospedali Galliera, 16128 Genoa, Italy"},{"name":"Wolfson Institute of Preventive Medicine, Queen Mary University of London, London E1 4NS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0140-6736(20)31187-9","article-title":"Clinical impact of COVID-19 on patients with cancer (CCC19): A cohort study","volume":"395","author":"Kuderer","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/S1470-2045(20)30442-3","article-title":"COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: A prospective cohort study","volume":"21","author":"Lee","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1177\/1745691621989243","article-title":"Psychological and Behavioral Predictors of Vaccine Efficacy: Considerations for COVID-19","volume":"16","author":"Madison","year":"2021","journal-title":"Perspect Psychol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.bbi.2011.10.009","article-title":"Vulnerability, distress, and immune response to vaccination in older adults","volume":"26","author":"Segerstrom","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.bbi.2009.01.004","article-title":"Psychological stress and antibody response to influenza vaccination: A meta-analysis","volume":"23","author":"Pedersen","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/978-1-4939-7828-1_16","article-title":"The Vaccination Model in Psychoneuroimmunology Research: A Review","volume":"1781","author":"Whittaker","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bbi.2022.04.017","article-title":"Social cohesion and loneliness are associated with the antibody response to COVID-19 vaccination","volume":"103","author":"Gallagher","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ejca.2021.09.030","article-title":"A Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment","volume":"159","author":"Buttiron","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1111\/bjh.16797","article-title":"Dynamic relationship between D-dimer and COVID-19 severity","volume":"190","author":"Li","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1055\/s-0041-1736168","article-title":"Cerebral Venous Thrombosis Developing after COVID-19 Vaccination: VITT, VATT, TTS, and More","volume":"48","author":"Lippi","year":"2022","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1007\/s11764-022-01291-z","article-title":"Effect of sex on psychological distress and fatigue over time in a prospective cohort of cancer survivors","volume":"18","author":"Rondanina","year":"2022","journal-title":"J. Cancer Surviv."},{"key":"ref_12","first-page":"1473","article-title":"Immune status and risk for infection in patients receiving chronic immunosuppressive therapy","volume":"32","author":"Kiefmann","year":"2005","journal-title":"J. Rheumatol."},{"key":"ref_13","unstructured":"National Comprehensive Cancer Network (2013). NCCN Clinical Practice Guidelines in Oncology: Distress Management, Version 1, NCCN."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/pon.1022","article-title":"Emotional distress: The sixth vital sign--future directions in cancer care","volume":"15","author":"Bultz","year":"2006","journal-title":"Psychooncology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/pon.3430","article-title":"Validation of the distress thermometer worldwide: State of the science","volume":"23","author":"Donovan","year":"2014","journal-title":"Psychooncology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1002\/cncr.27902","article-title":"Italian Society of Psycho-Oncology Distress Thermometer Study Group. Screening for distress in cancer patients: A multicenter, nationwide study in Italy","volume":"119","author":"Grassi","year":"2013","journal-title":"Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","article-title":"The hospital anxiety and depression scale","volume":"67","author":"Zigmond","year":"1983","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e01224-20","DOI":"10.1128\/JCM.01224-20","article-title":"Clinical and Analytical Performance of an Automated Serological Test That Identifies S1\/S2-Neutralizing IgG in COVID-19 Patients Semiquantitatively","volume":"58","author":"Bonelli","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_19","unstructured":"National SARS-CoV-2 Serology Assay Evaluation Group (2020). Performance characteristics of five immunoassays for SARS-CoV-2: A head-to-head benchmark comparison. Lancet Infect. Dis., 20, 1390\u20131400."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41594-020-0478-5","article-title":"A thermostable, closed SARS-CoV-2 spike protein trimer","volume":"27","author":"Xiong","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.thromres.2009.07.013","article-title":"Multicenter evaluation of a new quantitative highly sensitive D-dimer assay, the Hemosil D-dimer HS 500, in patients with clinically suspected venous thromboembolism","volume":"125","author":"Legnani","year":"2010","journal-title":"Thromb. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1470-2045(21)00213-8","article-title":"Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: Interim analysis of a prospective observational study","volume":"22","author":"Monin","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1515\/cclm-2022-0633","article-title":"D-dimer: Old dogmas, new (COVID-19) tricks","volume":"61","author":"Lippi","year":"2022","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2020.12.023","article-title":"Social psychoneuroimmunology: Understanding bidirectional links between social experiences and the immune system","volume":"93","author":"Muscatell","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-clinpsy-032816-045159","article-title":"Social Safety Theory: A Biologically Based Evolutionary Perspective on Life Stress, Health, and Behavior","volume":"16","author":"Slavich","year":"2020","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.bbi.2022.09.004","article-title":"Depressive symptoms predict antibody titers after a second dose of the SARS-CoV-2 BNT162b2 vaccine among hospital workers in Japan","volume":"107","author":"Kaneko","year":"2023","journal-title":"Brain Behav. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jad.2022.02.025","article-title":"Immune response to vaccination in adults with mental disorders: A systematic review","volume":"304","author":"Xiao","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.lanepe.2021.100253","article-title":"Adverse events of active and placebo groups in SARS-CoV-2 vaccine randomized trials: A systematic review","volume":"12","author":"Amanzio","year":"2022","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.bbi.2007.04.009","article-title":"Positive affective style covaries with stimulated IL-6 and IL-10 production in a middle-aged community sample","volume":"21","author":"Prather","year":"2007","journal-title":"Brain Behav. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"597600","DOI":"10.3389\/fnut.2020.597600","article-title":"The Impact of Obesity and Lifestyle on the Immune System and Susceptibility to Infections Such as COVID-19","volume":"7","author":"Atsma","year":"2020","journal-title":"Front. Nutr."},{"key":"ref_32","first-page":"1527","article-title":"Increasing Efficacy of Covid-19 Vaccines by Lifestyle Interventions","volume":"77","author":"Gasmi","year":"2022","journal-title":"Arch. Razi Inst."},{"key":"ref_33","first-page":"1031","article-title":"Psychosocial Interventions and Immune System Function: A Systematic Review and Meta-analysis of Randomized Clinical Trials","volume":"77","author":"Shields","year":"2020","journal-title":"J. Am. Med. Assoc. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1192\/bja.2021.9","article-title":"Psychosocial stress and immunosuppression in cancer: What can we learn from new research?","volume":"27","author":"Singh","year":"2021","journal-title":"BJPsych Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e0256406","DOI":"10.1371\/journal.pone.0256406","article-title":"COVID-19 vaccines and mental distress","volume":"16","author":"Angrisani","year":"2021","journal-title":"PLoS ONE"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e021007","DOI":"10.1136\/bmjopen-2017-021007","article-title":"Educational differences in psychological distress? Results from a population-based sample of men and women in Sweden in 2012","volume":"8","author":"Molarius","year":"2018","journal-title":"BMJ Open"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/23\/4012\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:43:00Z","timestamp":1760114580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/23\/4012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,29]]},"references-count":36,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["cancers16234012"],"URL":"https:\/\/doi.org\/10.3390\/cancers16234012","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2024,11,29]]}}}