Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada

BackgroundThe Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canadas larger provinces. MethodsTwo-dose VE against infections and hospitalizations due to SARS-CoV-2, including variants of concern, was assessed between May 30 and October 2, 2021 using test-negative designs separately conducted among community-dwelling adults [≥]18-years-old in British Columbia (BC) and Quebec, Canada. FindingsIn both provinces, two doses of homologous or heterologous SARS-CoV-2 vaccines were associated with [~]95% reduction in the risk of hospitalization. VE exceeded 90% against SARS-CoV-2 infection when at least one dose was an mRNA vaccine, but was lower at [~]70% when both doses were ChAdOx1. Estimates were similar by age group (including adults [≥]70-years-old) and for Delta-variant outcomes. VE was significantly higher against both infection and hospitalization with longer 7-8-week vs. manufacturer-specified 3-4-week interval between doses. Two-dose mRNA VE was maintained against hospitalization for the 5-7-month monitoring period and while showing some decline against infection, remained [≥]80%. InterpretationTwo doses of mRNA and/or ChAdOx1 vaccines gave excellent protection against hospitalization, with no sign of decline by 5-7 months post-vaccination. A 7-8-week interval between doses improved VE and may be optimal in most circumstances. Findings indicate prolonged two-dose protection and support the use of mixed schedules and longer intervals between doses, with global health, equity and access implications in the context of recent third-dose proposals.

Mutations in emerging variant of concern lineages disrupt genomic sequencing of SARS-CoV-2 clinical specimens

Mutations in emerging SARS-CoV-2 lineages can interfere with the laboratory methods used to generate high-quality genome sequences for COVID-19 surveillance. Here, we identify 46 mutations in current variant of concern lineages affecting the widely used laboratory protocols for SARS-CoV-2 genomic sequencing by Freed et al. and the ARTIC network. We provide laboratory data showing how three of these mutations disrupted sequencing of P.1 lineage specimens during a recent outbreak in British Columbia, Canada, and we also demonstrate how we modified the Freed et al. protocol to restore performance.