{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T15:29:57Z","timestamp":1764775797600,"version":"3.46.0"},"reference-count":24,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health Programma Ricerca Corrente 2026"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Cancer patients are particularly vulnerable to severe outcomes from COVID-19 due to immune suppression, treatment effects, and comorbidities. This population-based study aimed to assess how vaccination, circulating variants, and comorbidities influenced infections and severe disease risks in cancer patients compared with the general population. Methods: The study included 538,516 residents of Reggio Emilia Province, Italy, alive on 20 February 2020, followed until 30 September 2022. Cancer diagnoses (1996\u20132021) were obtained from the Reggio Emilia Cancer Registry and linked with COVID-19 surveillance, vaccination, hospitalization, and mortality data. Vaccination and prior infection were modelled as time-dependent variables. Hazard ratios for infection (HRs) and odds ratios for severe disease in those infected (ORs) were estimated using Cox and logistic regression models adjusting for sex, age, and comorbidities. Results: Among the 33,307 residents who had cancer, 9135 SARS-CoV-2 infections were recorded. Infection risk was similar to the general population before Omicron (HR 1.00; 95%CI 0.96\u20131.05) and slightly higher during Omicron (HR 1.08; 95%CI 1.05\u20131.11). Cancer patients showed higher probability of severe disease once infected (OR 1.33 pre-Omicron; 1.67 Omicron), with the greatest excess in recent diagnoses. Vaccination substantially reduced infections and severe outcomes in both groups in the pre-Omicron period; while only hybrid immunity reached high protection from Omicron infection. Conclusions: Vaccinations were effective in the populations with and without cancer; hybrid immunity conferred the strongest protection. However, because cancer patients, especially those recently diagnosed, retain a higher baseline risk of severe disease, vaccination yields even greater individual and public health benefits.<\/jats:p>","DOI":"10.3390\/vaccines13121223","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T15:02:48Z","timestamp":1764774168000},"page":"1223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing COVID-19 Infection and Severe Disease Risk in Cancer Patients and Survivors: The Role of Vaccination Status, Circulating Variants, and Comorbidities\u2014A Population-Based Study in Northern Italy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0227-2523","authenticated-orcid":false,"given":"Massimo","family":"Vicentini","sequence":"first","affiliation":[{"name":"Epidemiology Unit, Azienda USL-IRCCS of Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1609-2440","authenticated-orcid":false,"given":"Pamela","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Azienda USL-IRCCS of Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9190-8668","authenticated-orcid":false,"given":"Francesco","family":"Venturelli","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Azienda USL-IRCCS of Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Mezzadri","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eufemia","family":"Bisaccia","sequence":"additional","affiliation":[{"name":"Public Health Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Zerbini","sequence":"additional","affiliation":[{"name":"Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5089-5178","authenticated-orcid":false,"given":"Lucia","family":"Mangone","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Azienda USL-IRCCS of Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9703-2460","authenticated-orcid":false,"given":"Paolo","family":"Giorgi Rossi","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Azienda USL-IRCCS of Reggio Emilia, 42122 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Reggio Emilia COVID-19 Working Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,3]]},"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","unstructured":"Hwang, E.C., Hwang, J.E., Kim, K., Kim, S.J., Jung, J.H., Lee, H., Sun, K.H., and Han, M.A. (2025). Prognostic factors of mortality in patients with cancer infected with COVID-19: A systematic review and meta-analysis using the GRADE approach. Int. J. Cancer.","DOI":"10.1002\/ijc.70202"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/S1470-2045(20)30310-7","article-title":"Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: A multicentre, retrospective, cohort study","volume":"21","author":"Yang","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mangone, L., Gioia, F., Mancuso, P., Bisceglia, I., Ottone, M., Vicentini, M., Pinto, C., and Giorgi Rossi, P. (2021). Cumulative COVID-19 incidence, mortality and prognosis in cancer survivors: A population-based study in Reggio Emilia, Northern Italy. Front. Oncol., 11.","DOI":"10.1101\/2020.11.18.20233833"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Johannesen, T.B., Smeland, S., Aaserud, S., Buanes, E.A., Skog, A., Ursin, G., and Helland, \u00c5. (2021). COVID-19 in cancer patients, risk factors for disease and adverse outcome, a population-based study from Norway. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.652535"},{"key":"ref_6","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_7","first-page":"548","article-title":"Immune responses to two-dose SARS-CoV-2 mRNA vaccination in patients with solid tumors on active immunosuppressive therapy","volume":"7","author":"Shroff","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1001\/jamaoncol.2021.5148","article-title":"Evaluation of COVID-19 mortality and adverse outcomes in US patients with or without cancer","volume":"8","author":"Lei","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2200494","DOI":"10.2807\/1560-7917.ES.2023.28.13.2200494","article-title":"COVID-19 Working Group. Risk of SARS-CoV-2 reinfection by vaccination status, predominant variant and time from prior infection: A cohort study, Reggio Emilia province, Italy, February 2020 to February 2022","volume":"28","author":"Vicentini","year":"2023","journal-title":"Eurosurveillance"},{"key":"ref_10","first-page":"295","article-title":"The N501Y spike substitution enhances SARS-CoV-2 infection and transmission","volume":"593","author":"Liu","year":"2021","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa2119451","article-title":"COVID-19 vaccine effectiveness against the Omicron (B.1.1.529) variant","volume":"386","author":"Andrews","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e069052","DOI":"10.1136\/bmj-2021-069052","article-title":"Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe COVID-19 during predominant circulation of the delta variant in Italy: Retrospective cohort study","volume":"376","author":"Fabiani","year":"2022","journal-title":"BMJ"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2100429","DOI":"10.2807\/1560-7917.ES.2022.27.5.2100429","article-title":"COVID-19 National Microbiology Surveillance Study Group. Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021","volume":"27","author":"Stefanelli","year":"2022","journal-title":"Eurosurveillance"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2147\/CLEP.S271763","article-title":"Survival of Hospitalized COVID-19 Patients in Northern Italy: A Population-Based Cohort Study by the ITA-COVID-19 Network","volume":"12","author":"Ferroni","year":"2020","journal-title":"Clin. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mangone, L., Giorgi Rossi, P., Taborelli, M., Toffolutti, F., Mancuso, P., Dal Maso, L., Gobbato, M., Clagnan, E., Del Zotto, S., and Ottone, M. (2023). SARS-CoV-2 infection, vaccination and risk of death in people with an oncological disease in northeast Italy. J. Pers. Med., 13.","DOI":"10.3390\/jpm13091333"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1200\/JCO.24.00032","article-title":"Vaccination of adults with cancer: ASCO guideline","volume":"42","author":"Kamboj","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1002\/jmv.27956","article-title":"Impaired serological response to COVID-19 vaccination following anticancer therapy: A systematic review and meta-analysis","volume":"94","author":"Tang","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejca.2022.05.031","article-title":"Predictors of poor serologic response to COVID-19 vaccine in patients with cancer: A systematic review and meta-analysis","volume":"172","author":"Yang","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1093\/infdis\/jiad174","article-title":"COVID-19 vaccination in patients with cancer and patients receiving HSCT or CAR-T therapy: Immune response, real-world effectiveness, and implications for the future","volume":"228","author":"Hall","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ejca.2022.02.017","article-title":"Limited T cell response to SARS-CoV-2 mRNA vaccine among patients with cancer receiving different cancer treatments","volume":"166","author":"Casado","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Almasri, M., Bshesh, K., Khan, W., Mushannen, M., Salameh, M.A., Shafiq, A., Vattoth, A.L., Elkassas, N., and Zakaria, D. (2022). Cancer patients and the COVID-19 vaccines: Considerations and challenges. Cancers, 14.","DOI":"10.3390\/cancers14225630"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/S1470-2045(21)00574-X","article-title":"mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours: A prospective, multicentre, non-inferiority trial","volume":"22","author":"Oosting","year":"2021","journal-title":"Lancet Oncol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/12\/1223\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T15:26:44Z","timestamp":1764775604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/12\/1223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":24,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["vaccines13121223"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13121223","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,3]]}}}