• Giovanni Corrao, Matteo Franchi, Danilo Cereda, Francesco Bortolan, Olivia Leoni, Jose Jara, Giuseppina Valenti, and Giovanni Pavesi.
• National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy.
• J. Intern. Med. 2022 Nov 1; 292 (5): 829836829-836.

BackgroundLittle is known about vulnerability to severe COVID-19 illness after vaccination completion with three doses of vaccine against COVID-19.ObjectivesTo identify individual features associated with increased risk of severe clinical manifestation of SARS-CoV-2 infections after receiving the third dose of vaccine against COVID-19.MethodsWe performed a nested case-control study based on 3,360,116 citizens from Lombardy, Italy, aged 12 years or older who received the third dose of vaccine against COVID-19 from 20 September through 31 December 2021. Individuals were followed from 14 days after vaccination completion until the occurrence of severe COVID-19 illness, death unrelated to COVID-19, emigration or 15 March 2022. For each case, controls were randomly selected to be 1:10 matched for the date of vaccination completion and municipality of residence. The association between candidate predictors and outcome was assessed through multivariable conditional logistic regression models.ResultsDuring 12,538,330 person-months of follow-up, 5171 cases of severe illness occurred. As age increased, a trend towards increasing odds of severe illness was observed. Male gender was a significant risk factor. As the number of contacts with the Regional Health Service increased, a trend towards increasing odds of severe illness was observed. Having had a previous SARS-CoV-2 infection was a significant protective factor. Having received the Moderna vaccine significantly decreased the odds of severe illness. Significant higher odds were associated with 42 diseases/conditions. Odds ratios ranged from 1.23 (diseases of the musculoskeletal system) to 5.00 (autoimmune disease).ConclusionsThis study provides useful insights for establishing priority in fourth-dose vaccination programs.© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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