tetano
Editor, Senior Moderator
Vaccine
. 2026 Oct 13:94:129234.
doi: 10.1016/j.vaccine.2026.129234. Online ahead of print.
Diogo F P Marques 1 , Jennifer Howard 2 , Marcos Lozano Álvarez 3 , Ausenda Machado 4 , Róisín Duffy 5 , Gergő Túri 6 , Monika Kuliese 7 , Odette Popovici 8 , Goranka Petrović 9 , Adrien Lajot 10 , Ralf Dürrwald 11 , John Paul Cauchi 12 , Camino Trobajo-Sanmartín 13 , Petr Husa 14 , Francisco Pozo 15 , Nuno Verdasca 16 , Eva Rivas Wagner 17 , Verónica Gómez 4 , Margaret Fitzgerald 5 , Beatrix Oroszi 6 , Ligita Jančorienė 18 , Mihaela Lazar 19 , Irena Tabain 9 , Francesco G Genderini 20 , Carolin Hackmann 21 , Aušra Džiugytė 22 , Aitziber Echeverria 13 , Lenka Součková 14 , Nathalie Nicolay 23 , Sabrina Bacci 23 , Baltazar Nunes 24 , Angela M C Rose 2 ; VEBIS hospital network
Affiliations Expand
Introduction: Two severe acute respiratory infection (SARI) case definitions (CDs) are often used in test-negative design (TND) hospital-based vaccine effectiveness (VE) studies. SARI-CD1 requires ≥1 symptom (cough, fever, shortness of breath, anosmia, ageusia, or dysgeusia); SARI-CD2 requires both fever and cough. Using VEBIS hospital network end-of-season 2023/24 data, we compared the effect of these CDs on influenza and COVID-19 VE estimates in Europe.
Methods: Using the TND, we restricted analysis to seven countries recruiting patients using SARI-CD1; we created a subset of SARI patients also meeting SARI-CD2. Cases were RT-PCR-positive for influenza A(H1N1)pdm09, A(H3N2), or SARS-CoV-2; controls were influenza or SARS-CoV-2 RT-PCR-negative. We estimated VE among patients ≥65 years using logistic regression adjusted for country, onset date, age, sex, and chronic conditions. We estimated VE overall, by age group (65-79, ≥80 years) and time since vaccination (14-59, 60-119, ≥120 days). Absolute VE differences ≥10% were considered relevant.
Results: Patient characteristics and outcomes were similar across CDs. SARI-CD1 had slightly more vaccinated cases, with little difference in controls between the two CDs. For influenza, the absolute VE difference between SARI-CD1 and SARI-CD2 was 10% for influenza A(H1N1)pdm09 (34% vs 44%), 19% among those aged ≥80 years (21% vs 40%) and 18% at 60-119 days post-vaccination (4% vs 22%). For SARS-CoV-2, absolute VE differences were 11% overall (29% vs 40%), 11% among ≥80 years (33% vs 44%), and 12% at 60-119 days (34% vs 46%). All other absolute VE differences were < 10%.
Conclusions: VE was similar for influenza A(H3N2), adults 65-79 years and 14-60 days post-vaccination. We observed signals of higher VE with SARI-CD2 for influenza A(H1N1)pdm09 and SARS-CoV-2, particularly among adults ≥80 years and ≥ 60 days post-vaccination, although 95% CIs overlapped. These signals suggest CDs may contribute to VE variability and VE studies should clearly indicate CDs used.
Keywords: Case definitions; Multicentre study; Severe acute respiratory infection (SARI); Test-negative design; Vaccine effectiveness.
. 2026 Oct 13:94:129234.
doi: 10.1016/j.vaccine.2026.129234. Online ahead of print.
Comparing two case definitions for including severe acute respiratory infection patients in influenza and COVID-19 vaccine effectiveness studies among older adults using the test-negative design: VEBIS hospital network, seven European countries, 2023/24
Diogo F P Marques 1 , Jennifer Howard 2 , Marcos Lozano Álvarez 3 , Ausenda Machado 4 , Róisín Duffy 5 , Gergő Túri 6 , Monika Kuliese 7 , Odette Popovici 8 , Goranka Petrović 9 , Adrien Lajot 10 , Ralf Dürrwald 11 , John Paul Cauchi 12 , Camino Trobajo-Sanmartín 13 , Petr Husa 14 , Francisco Pozo 15 , Nuno Verdasca 16 , Eva Rivas Wagner 17 , Verónica Gómez 4 , Margaret Fitzgerald 5 , Beatrix Oroszi 6 , Ligita Jančorienė 18 , Mihaela Lazar 19 , Irena Tabain 9 , Francesco G Genderini 20 , Carolin Hackmann 21 , Aušra Džiugytė 22 , Aitziber Echeverria 13 , Lenka Součková 14 , Nathalie Nicolay 23 , Sabrina Bacci 23 , Baltazar Nunes 24 , Angela M C Rose 2 ; VEBIS hospital network
Affiliations Expand
- PMID: 42869874
- DOI: 10.1016/j.vaccine.2026.129234
Abstract
Introduction: Two severe acute respiratory infection (SARI) case definitions (CDs) are often used in test-negative design (TND) hospital-based vaccine effectiveness (VE) studies. SARI-CD1 requires ≥1 symptom (cough, fever, shortness of breath, anosmia, ageusia, or dysgeusia); SARI-CD2 requires both fever and cough. Using VEBIS hospital network end-of-season 2023/24 data, we compared the effect of these CDs on influenza and COVID-19 VE estimates in Europe.
Methods: Using the TND, we restricted analysis to seven countries recruiting patients using SARI-CD1; we created a subset of SARI patients also meeting SARI-CD2. Cases were RT-PCR-positive for influenza A(H1N1)pdm09, A(H3N2), or SARS-CoV-2; controls were influenza or SARS-CoV-2 RT-PCR-negative. We estimated VE among patients ≥65 years using logistic regression adjusted for country, onset date, age, sex, and chronic conditions. We estimated VE overall, by age group (65-79, ≥80 years) and time since vaccination (14-59, 60-119, ≥120 days). Absolute VE differences ≥10% were considered relevant.
Results: Patient characteristics and outcomes were similar across CDs. SARI-CD1 had slightly more vaccinated cases, with little difference in controls between the two CDs. For influenza, the absolute VE difference between SARI-CD1 and SARI-CD2 was 10% for influenza A(H1N1)pdm09 (34% vs 44%), 19% among those aged ≥80 years (21% vs 40%) and 18% at 60-119 days post-vaccination (4% vs 22%). For SARS-CoV-2, absolute VE differences were 11% overall (29% vs 40%), 11% among ≥80 years (33% vs 44%), and 12% at 60-119 days (34% vs 46%). All other absolute VE differences were < 10%.
Conclusions: VE was similar for influenza A(H3N2), adults 65-79 years and 14-60 days post-vaccination. We observed signals of higher VE with SARI-CD2 for influenza A(H1N1)pdm09 and SARS-CoV-2, particularly among adults ≥80 years and ≥ 60 days post-vaccination, although 95% CIs overlapped. These signals suggest CDs may contribute to VE variability and VE studies should clearly indicate CDs used.
Keywords: Case definitions; Multicentre study; Severe acute respiratory infection (SARI); Test-negative design; Vaccine effectiveness.