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Immunol Res . Association between COVID-19 booster vaccination and influenza mortality: a nationwide retrospective cohort study using the SIVEP-Gri

tetano

Editor, Senior Moderator
Immunol Res


. 2026 Jun 22;74(1):62.
doi: 10.1007/s12026-026-09792-0.
Association between COVID-19 booster vaccination and influenza mortality: a nationwide retrospective cohort study using the SIVEP-Gripe database in Brazil

Daniele Melo Sardinha[SUP] 1 2 3 [/SUP], Natália Melazo Machado Neves[SUP] 4 [/SUP], Tamires de Nazaré Soares[SUP] 1 [/SUP], Marcos Jessé Abrahão Silva[SUP] 1 [/SUP], Lidiane Assunção de Vasconcelos[SUP] 1 [/SUP], Luany Rafaele da Conceição Cruz[SUP] 5 [/SUP], Karina Faine Freitas Takeda[SUP] 6 [/SUP], Natasha Cristina Oliveira Andrade[SUP] 1 [/SUP], Suziane do Socorro Dos Santos[SUP] 1 [/SUP], Felipe Costa Soares[SUP] 7 [/SUP], Neiva José da Luz Dias Júnior[SUP] 7 [/SUP], Yan Corrêa Rodrigues[SUP] 8 [/SUP], Ilma Pastana Ferreira[SUP] 7 [/SUP], Mônica Custódia do Couto Abreu Pamplona[SUP] 7 [/SUP], Ivonete Vieira Pereira Peixoto[SUP] 7 [/SUP], Luana Nepomuceno Gondim Costa Lima[SUP] 1 2 3 [/SUP]


Affiliations
Abstract

To identify clinical and epidemiological predictors of mortality among patients hospitalized with laboratory-confirmed influenza in Brazil during 2024, and to evaluate the association of vaccination and antiviral therapy with clinical outcomes. We conducted a nationwide retrospective cohort study using the Brazilian SIVEP-Gripe surveillance database. All hospitalized patients with RT-PCR-confirmed influenza and known outcomes were included. Multivariable logistic regression was initially performed to explore predictors of mortality. To more rigorously assess the association between COVID-19 booster vaccination and mortality, a propensity score-based inverse probability of treatment weighting (IPTW) approach was applied, with weights truncated at 10. E-values were calculated to assess robustness to unmeasured confounding. A total of 15,995 hospitalized influenza cases were included, with an overall case fatality rate of 12.1%. Influenza A predominated (88.0%) and was associated with higher mortality than Influenza B. In IPTW-weighted models, COVID-19 booster vaccination remained independently associated with reduced mortality (OR 0.90, 95% CI 0.84-0.97; p = 0.007). Additional risk factors included dyspnea, respiratory distress, and low oxygen saturation, as well as comorbidities such as obesity, diabetes, liver disease, and immunosuppression. Protective factors included influenza vaccination (OR 0.77) and oseltamivir use (OR 0.81). The model demonstrated good discrimination (AUC = 0.81, 95% CI 0.80-0.82). The E-value for the booster association was 1.46, indicating moderate robustness to unmeasured confounding. Influenza mortality in Brazil is primarily driven by age, comorbidities, and clinical severity at presentation, but is significantly mitigated by vaccination and antiviral therapy. The observed association between COVID-19 booster vaccination and reduced mortality suggests a possible heterologous immune effect, although causality cannot be established. These findings support integrated immunization strategies targeting multiple respiratory pathogens.

Keywords: Booster Dose; Brazil; COVID-19 Vaccines; Cohort Studies; Heterologous Immunity; Influenza, Human; Mortality; SIVEP-Gripe.

 
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