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Vaccine
. 2026 Jun 12:88:128806.
doi: 10.1016/j.vaccine.2026.128806. Online ahead of print.
Safety of influenza vaccine during the vaccination campaign 2021/2022 in Italy: a self-controlled case series study
Stefania Spila-Alegiani 1 , Marco Massari 1 , Maria Cutillo 2 , Francesca Menniti-Ippolito 1 , Roberto Da Cas 1 , Flavia Mayer 1 , Giuseppe Marano 1 , Valeria Belleudi 3 , Antonio Addis 3 , Valeria Desiderio 4 , Nadia Mores 5 , Sara Lopes 3 , Maria Balducci 3 , Lucian Ejlli 6 , Stefania Del Zotto 7 , Elena Clagnan 7 , Sarah Samez 6 , Cristina Zappetti 6 , Paola Rossi 6 , Ester Sapigni 8 , Aurora Puccini 8 , Marco Villa 9 , Claudio Visigalli 9 , Gianluca Trifirò 10 , Nicoletta Luxi 11 , Cristina Morciano 1
Affiliations
Introduction: This study evaluated the safety of influenza vaccines in a large and representative population during the 2021/2022 campaign in Italy using a Self-Controlled Case Series (SCCS) design using regional health data registries.
Methods: This multiregional study used healthcare data to assess pre-specified potential adverse outcomes after flu vaccination during the 2021/2022 season. Participants were individuals aged 6 months or older, vaccinated or not, admitted to emergency care or hospital for at least one of the incident outcomes of interest. Risk periods were specifically defined for each outcome and compared to reference periods. The Self-Controlled Case Series design modified for event-dependent exposures was used, estimating relative incidences and excess cases by age, sex, dose, and adjusting for calendar time.
Results: No increased risks were observed for most of the study outcomes. An increased risk of thrombocytopenia (RI = 1.90; 95% CI: 1.00-3.61) and optic nerve neuritis (RI = 5.22; 95% CI: 1.31-20.79) was detected within 42 days after vaccination in individuals under 60 years. Sensitivity and ancillary analyses supported these findings.
Conclusions: These findings confirm the overall safety of influenza vaccines during the 2021/2022 campaign, with no evidence of increased risk for most of the pre-specified adverse outcomes. The increased risks observed for thrombocytopenia and optic neuritis need further research.
Keywords: Adverse drug events; Influenza vaccine; Post-marketing drug surveillance; Routinely collected health data; Self-controlled case series.
. 2026 Jun 12:88:128806.
doi: 10.1016/j.vaccine.2026.128806. Online ahead of print.
Safety of influenza vaccine during the vaccination campaign 2021/2022 in Italy: a self-controlled case series study
Stefania Spila-Alegiani 1 , Marco Massari 1 , Maria Cutillo 2 , Francesca Menniti-Ippolito 1 , Roberto Da Cas 1 , Flavia Mayer 1 , Giuseppe Marano 1 , Valeria Belleudi 3 , Antonio Addis 3 , Valeria Desiderio 4 , Nadia Mores 5 , Sara Lopes 3 , Maria Balducci 3 , Lucian Ejlli 6 , Stefania Del Zotto 7 , Elena Clagnan 7 , Sarah Samez 6 , Cristina Zappetti 6 , Paola Rossi 6 , Ester Sapigni 8 , Aurora Puccini 8 , Marco Villa 9 , Claudio Visigalli 9 , Gianluca Trifirò 10 , Nicoletta Luxi 11 , Cristina Morciano 1
Affiliations
- PMID: 42284809
- DOI: 10.1016/j.vaccine.2026.128806
Introduction: This study evaluated the safety of influenza vaccines in a large and representative population during the 2021/2022 campaign in Italy using a Self-Controlled Case Series (SCCS) design using regional health data registries.
Methods: This multiregional study used healthcare data to assess pre-specified potential adverse outcomes after flu vaccination during the 2021/2022 season. Participants were individuals aged 6 months or older, vaccinated or not, admitted to emergency care or hospital for at least one of the incident outcomes of interest. Risk periods were specifically defined for each outcome and compared to reference periods. The Self-Controlled Case Series design modified for event-dependent exposures was used, estimating relative incidences and excess cases by age, sex, dose, and adjusting for calendar time.
Results: No increased risks were observed for most of the study outcomes. An increased risk of thrombocytopenia (RI = 1.90; 95% CI: 1.00-3.61) and optic nerve neuritis (RI = 5.22; 95% CI: 1.31-20.79) was detected within 42 days after vaccination in individuals under 60 years. Sensitivity and ancillary analyses supported these findings.
Conclusions: These findings confirm the overall safety of influenza vaccines during the 2021/2022 campaign, with no evidence of increased risk for most of the pre-specified adverse outcomes. The increased risks observed for thrombocytopenia and optic neuritis need further research.
Keywords: Adverse drug events; Influenza vaccine; Post-marketing drug surveillance; Routinely collected health data; Self-controlled case series.