SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021-Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing

Abstract

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs.

Keywords: COVID-19; N501Y; SARS-CoV-2; Switzerland; molecular epidemiology; mutation; sequencing; surveillance; variant.

Figure 1

Diagnostic strategy to detect the B.1.1.7 and the B.1.351 in Switzerland. The flowchart shows the three-step strategy with (i) initial epidemiological case definitions with travels from the UK or South Africa, (ii) the diagnostic evidence due to a S gene dropout and (iii) the final establishment of a N501Y-specific PCR. In all steps amplicon based and whole genome sequencing was used to determine and confirm the lineage allocation.

Figure 2

Distribution of absolute numbers as epidemiological curves across Switzerland. solute numbers reflect a biased sample set due to the initial case definitions, higher usage of antigen test in some regions, and distribution of diagnostic capacities. This does not reflect the prevalence of cases. The current number of specific lineages is also biased due to different sequencing capacities. “Lineage unclear” includes isolates which show a N501Y mutation, but where the lineage could not be determined by sequencing, either due to technical difficulties or due to non-availability of the sample.

Figure 3

Phylogeny of sequenced B.1.1.7 cases in Switzerland. (A) Geographic distribution through Switzerland and (B) phylogenetic relationship of 675 genomes dating between 30 November 2020 and 11 February 2021 from the Geneva University Hospitals (n = 574), University Hospital Lausanne (n = 44), University Hospital Basel (n = 70), University of Bern (n = 10), University of Zurich (n = 14), and ETH Zurich (n = 20), Center for Laboratory Medicine St. Gallen (n = 1), Philip Morris International (n = 6). X-Axis scales to time. (C) Zoom into an exemplar, possible cryptic transmissions within a cluster, and single introductions, scale by mutations distance to the reference Wuhan/Hu1-1.