Interim 2025/26 LP.8.1 vaccine effectiveness estimates against COVID-19 from the Canadian Sentinel Practitioner Surveillance Network (SPSN): insights into possible impact of influenza and other respiratory virus co-circulation

BACKGROUND The Canadian Sentinel Practitioner Surveillance Network routinely undertakes multiplex respiratory virus testing, vaccine effectiveness (VE) estimation by test-negative design (TND), and whole genome sequencing (WGS) of vaccine-targeted viruses. AIM To estimate 2025/26 LP.8.1 VE against community-based COVID-19, including variant-specific, and explore the impact of other respiratory viruses among COVID-19 cases and/or controls. METHODS Participants were ≥ 12-year-old outpatients presenting with acute respiratory illness between 26 October 2025 and 07 March 2026. COVID-19 vaccination information was registry-based. Primary TND analyses excluded influenza virus-infected controls. Sensitivity analyses explored inclusion and/or exclusion of influenza and other respiratory viral infections among COVID-19 cases and/or controls. WGS supported VE interpretation and variant-specific estimation. RESULTS We included 3,802 participants (2,832 (74%) aged 12–64 years; 970 (26%) aged ≥ 65 years), with 310 COVID-19 cases (29 vaccinated; 9%) and 3,492 controls (577 vaccinated; 17%). At median 9 weeks post-vaccination, LP.8.1 VE was 48% (95%CI: 21 to 66): 44% (95%CI: −12 to 72) for 12–64 and 53% (95%CI: 21 to 73) for ≥ 65-year-olds. In sensitivity analyses, VE was stable for ≥ 65-year-olds. Among 12–64-year-olds, VE decreased when including influenza virus infections among controls but increased when excluding co-infections, recognising uncertainty with reduced sample size. Against viruses that failed vs succeeded WGS, VE was 26% (95%CI: −63 to 66) vs 53% (95%CI: 24 to 71), 63% (95%CI: 30 to 80) against the XFG variant. Most SARS-CoV-2 co-infections with semi-quantification, including those failing WGS, showed higher viral load for the non-SARS-CoV-2 infection. CONCLUSION The 2025/26 LP.8.1 vaccine approximately halved the medically attended COVID-19 risk. Multiplex testing to identify primary co-infections among cases, or correlated vaccine-preventable infections among controls, may address VE under-estimation.