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

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.

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Journal
Vaccine
Published
2026-10-13
DOI
https://doi.org/10.1016/j.vaccine.2026.129234
Primary Topic
Influenza Virus Research Studies
Type
article
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article

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

Mihaela Lazăr, Diogo FP Marques, Petr Husa, Adrien Lajot et al.
Vaccine
Influenza Virus Research Studies
article

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

Mihaela Lazăr, Diogo FP Marques, Petr Husa, Adrien Lajot, Nuno Verdasca, Gergő Túri, Goranka Petrović, Irena Tabain, Francesco Genderini, John Paul Cauchi, Lenka Součková, Beatrix Oroszi, Aušra Džiugytė, Francisco Pozo, Ralf Dürrwald, Monika Kuliešė, Odette Popovici, Sabrina Bacci, Ausenda Machado, Nathalie Nicolay, Angela MC Rose, Jennifer Howard, Carolin Hackmann, Eva Rivas Wagner, Ligita Jančorienė, Camino Trobajo‐Sanmartín, Margaret G. Fitzgerald, Marcos Lozano Álvarez, Baltazar Nunes, Róisín Duffy, Aitziber Echeverría, Verónica Gómez
article en

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.

VaccineVol. 94
Semmelweis University (HU), Lithuanian University of Health Sciences (LT), Vilnius University (LT), University of Malta (MT), Masaryk University (CZ), Robert Koch Institute (DE), Instituto de Salud Carlos III (ES), Health Service Executive (IE), Instituto de Salud Pública de Navarra (ES), Institutul National de Sanatate Publica (RO), National School of Public Health (GR), Hrvatski zavod za javno zdravstvo (HR), Institutul Cantacuzino (RO), Health Protection Surveillance Centre (IE), Direccion General de Epidemiologia (MX), National Institute of Health Dr. Ricardo Jorge (PT), Sciensano (Belgium) (BE), Centre Hospitalier Universitaire de Saint-Pierre (BE), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), European Centre for Disease Prevention and Control (SE)
Good health and well-being
Openalex Percentile: Top 13%
Influenza Virus Research Studies
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