SARS-CoV-2 testing and sequencing for international arrivals reveals significant cross border transmission of high risk variants into the United Kingdom

Abstract

Background Mandatory Day 2 and Day 8 PCR testing and variant sequencing of international arrivals has been recently introduced by the UK Government to mitigate against cross-border transmission of high-risk SARS-CoV-2 variants. Methods SARS-CoV-2 testing and sequencing combines TaqPath CE-IVD COVID-19 RT-PCR with Ion AmpliSeq SARS-CoV-2 Next Generation Sequencing Assay. Retrospective analysis of test trending data was performed from initiation of testing on the 11th March through to the 14th April 2021. Findings During this time interval, 203,065 SARS-CoV-2 PCR tests were performed, with 3,855 samples testing positive, giving a prevalence of 1.9%. In total 1,913 SARS-CoV-2 genomes were sequenced from positive cases with Ct values < 30 and 1,635 (85.5%) sequences passed quality metrics for lineage analysis. A high diversity of 49 different SARS-CoV-2 variants were identified, including the VOCs B.1.1.7 (Kent; 80.6%), B.1.351 (South Africa; 4.2%), B.1.617.2 (India; 1.7%), P.1 (Brazil; 0.4%) and B.1.1.7 with E484K (Bristol; 0.2%). Vaccine effectiveness was age-related and dose-dependent, ranging from 5% in > 60 with a single dose to 83% in <60 with both doses of a vaccine. Viral load was variant dependent with the B.1.617.2 showing a 21 fold increase in viral copy number compared to the other variants. Interpretation The unexpectedly high prevalence of COVID-19 infection in UK arrivals is associated with a rich diversity of SARS-CoV-2 high risk variants entering the UK including the VOC B.1.617.2. Vaccination does not preclude infection and its effectiveness is significantly age-dependent and impacted by variant type. The rapid high-throughput test and sequence workflow we have adopted is particularly suited to the monitoring of cross border transmission and enables immediate public health interventions. Funding Data analysis conducted in this study was limited to secondary use of information previously collected in the course of normal care.

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“…Previous reports of in-house-selective assays, as well as commercial variant detection kits, rely mostly on the identification of common mutations that are not specific to a particular variant ( 22 – 24 ). Other variant of concern (VOC) detection approaches rely on multistep expensive procedures ( 25 , 26 ). Such assays are not suitable for rapid determination of the identity of an examined sample based on a single assay.…”

Specific Detection of Sars-Cov-2 Variants B.1.1.7 (Alpha) and B.1.617.2 (Delta) Using a One-Step Quantitative PCR Assay

“…Previous reports of in-house selective assays, as well as commercial variant detection kits, rely mostly on the identification of common mutations that are not specific to a single variant (Migueres et al 2021, Lu et al 2021, Zelyas et al 2021. Other VOC detection approaches rely on multi-step expensive procedures (Williams et al 2021, Tierling et al 2021). Such assays are not suitable for rapid determination the identity of an examined sample, based on a single assay.…”

“…This assay was also used for screening international arrivals, which is particularly important when attempting to prevent the spreading of new variants. While other reported approaches to detect SC-2 variants in international travelers rely on lengthy multi-step procedures [24,25] this assay is rapid (~80 minutes from extraction to answer) and can be implemented in most standard laboratories that perform routine PCR tests. This is particularly advantageous when an accelerated epidemiological investigation or other actions need to be taken, and complete genomic analysis is not available.…”