The SARS-CoV-2 lineages B.1.1.7 and 501.V2, which were first detected in the United Kingdom and South Africa, respectively, are spreading rapidly in the human population. Thus, there is an increased need for genomic and epidemiological surveillance in order to detect the strains and estimate their abundances. Here, we report a genomic analysis of SARS-CoV-2 in 48 raw wastewater samples collected from three wastewater treatment plants in Switzerland between July 9 and December 21, 2020. We find evidence for the presence of several mutations that define the B.1.1.7 and 501.V2 lineages in some of the samples, including co-occurrences of up to three B.1.1.7 signature mutations on the same amplicon in four samples from Lausanne and one sample from a Swiss ski resort dated December 9 - 21. These findings suggest that the B.1.1.7 strain could be detected by mid December, two weeks before its first verification in a patient sample from Switzerland. We conclude that sequencing SARS-CoV-2 in community wastewater samples may help detect and monitor the circulation of diverse lineages.

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Detection of SARS-CoV-2 variants in Switzerland by genomic analysis of wastewater samples

The continuing emergence of SARS-CoV-2 variants of concern and variants of interest emphasizes the need for early detection and epidemiological surveillance of novel variants. We used genomic sequencing of 122 wastewater samples from three locations in Switzerland to monitor the local spread of B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2 at a population level. We devised a bioinformatics method named COJAC (Co-Occurrence adJusted Analysis and Calling) that uses read pairs carrying multiple variant-specific signature mutations as a robust indicator of low-frequency variants. Application of COJAC revealed that a local outbreak of the Alpha variant in two Swiss cities was observable in wastewater up to 13 d before being first reported in clinical samples. We further confirmed the ability of COJAC to detect emerging variants early for the Delta variant by analysing an additional 1,339 wastewater samples. While sequencing data of single wastewater samples provide limited precision for the quantification of relative prevalence of a variant, we show that replicate and close-meshed longitudinal sequencing allow for robust estimation not only of the local prevalence but also of the transmission fitness advantage of any variant. We conclude that genomic sequencing and our computational analysis can provide population-level estimates of prevalence and fitness of emerging variants from wastewater samples earlier and on the basis of substantially fewer samples than from clinical samples. Our framework is being routinely used in large national projects in Switzerland and the UK. 

/pdf/early-detection-and-surveillance-of-sars-cov-2-genomic-3vck83rv.pdf

Early detection and surveillance of SARS-CoV-2 genomic variants in wastewater using COJAC

Several SARS-CoV-2 variants of concern (VOC) are spreading rapidly in different regions of the world. The underlying mechanisms behind their transmission advantage remain unclear. We measured viral load in 950 individuals and found that infections with variant Alpha exhibit a higher viral load and longer viral shedding compared to non-VOC. We then used a transmission model to analyze the spread of variant Alpha in Geneva, Switzerland, and variant Beta in South Africa. We estimated that Alpha is either associated with a 37% (95% compatibility interval, CI: 25–63%) increase in transmissibility or a 51% (95% CI: 32–80%) increase of the infectious duration, or a combination of the two mechanisms. Assuming 50% immune evasion for Beta, we estimated a 23% (95% CI: 10–37%) increase in transmissibility or a 38% (95% CI: 15–78%) increase of the infectious duration for this variant. Beta is expected to outgrow Alpha in regions where the level of naturally acquired immunity from previously circulating variants exceeds 20% to 40%. Close monitoring of Alpha and Beta in regions with different levels of immunity will help to anticipate the global spread of these and future variants.

/pdf/a-tale-of-two-variants-spread-of-sars-cov-2-variants-alpha-2hxm2djfhc.pdf

A tale of two variants: Spread of SARS-CoV-2 variants Alpha in Geneva, Switzerland, and Beta in South Africa

The emergence of a novel SARS-CoV-2 B.1.1.7 variant sparked global alarm due to increased transmissibility, mortality, and uncertainty about vaccine efficacy, thus accelerating efforts to detect and track the variant. Current approaches to detect B.1.1.7 include sequencing and RT-qPCR tests containing a target assay that fails or results in reduced sensitivity towards the B.1.1.7 variant. Since many countries lack genomic surveillance programs and failed assays detect unrelated variants containing similar mutations as B.1.1.7, we used allele-specific PCR, and judicious placement of LNA-modified nucleotides to develop an RT-qPCR test that accurately and rapidly differentiates B.1.1.7 from other SARS-CoV-2 variants. We validated the test on 106 clinical samples with lineage status confirmed by sequencing and conducted a country-wide surveillance study of B.1.1.7 prevalence in Slovakia. Our multiplexed RT-qPCR test showed 97% clinical sensitivity and retesting 6,886 SARS-CoV-2 positive samples obtained during three campaigns performed within one month, revealed pervasive spread of B.1.1.7 with an average prevalence of 82%. Labs can easily implement this test to rapidly scale B.1.1.7 surveillance efforts and it is particularly useful in countries with high prevalence of variants possessing only the ΔH69/ΔV70 deletion because current strategies using target failure assays incorrectly identify these as putative B.1.1.7 variants.

/pdf/surveillance-of-sars-cov-2-lineage-b-1-1-7-in-slovakia-using-4zzq7mwdlb.pdf

Surveillance of SARS-CoV-2 lineage B.1.1.7 in Slovakia using a novel, multiplexed RT-qPCR assay.

Impact of vaccination and non-pharmaceutical interventions on SARS-CoV-2 dynamics in Switzerland

https://www.dora.lib4ri.ch/eawag/islandora/object/eawag%3A23581/datastream/PDF/Chen-2021-Quantification_of_the_spread_of-%28published_version%29.pdf

Quantification of the spread of SARS-CoV-2 variant B.1.1.7 in Switzerland.

Background In December 2020, the United Kingdom (UK) reported a SARS-CoV-2 Variant of Concern (VoC) which is now coined B.1.1.7. Based on the UK data and later additional data from other countries, a transmission advantage of around 40-80% was estimated for this variant [1, 2, 3]. Aim The goal of this study is to estimate the transmission fitness advantage and the effective reproductive number of B.1.1.7 through time for data from Switzerland. Methods We collected genomic surveillance data from 11.8% of all SARS-CoV-2 confirmed cases across Switzerland between 14.12.2020 and 11.03.2021. It allows us to determine the relative proportion of the B.1.1.7 variant on a daily basis and to quantify the transmission advantage of the B.1.1.7 variant on a national and a regional scale. Results We propose a transmission advantage of 43-52% of B.1.1.7 compared to the other circulating variants. Further, we estimate a reproductive number for B.1.1.7 above 1 for Jan. 1, 2021 until now while the reproductive number for the other variants was below 1. In particular, for the time period up to Jan. 17 we obtain a reproductive number of 1.24 [1.07-1.41] and from Jan. 18 until March 1 we obtain 1.18 [1.06-1.30] based on the whole genome sequencing data. For March 10-16, we obtain 1.14 [1.00-1.26] based on all confirmed cases among which B.1.1.7 is dominant at this stage. Switzerland tightened measures on 18.01.2021 and released measures on 01.03.2021. Conclusion In summary, the dynamics of increase in the frequency of B.1.1.7 is as expected based on the observations in the UK. B.1.1.7 increased in absolute numbers exponentially with the point estimate for the doubling time being around 2-3.5 weeks. Our plots are available online and are currently regularly updated with new data to closely monitor the spread of B.1.1.7.

/pdf/quantification-of-the-spread-of-sars-cov-2-variant-b-1-1-7-2b2ckked5k.pdf

Laura Neff

Papers

Quantification of the spread of SARS-CoV-2 variant B.1.1.7 in Switzerland.

Quantification of the spread of SARS-CoV-2 variant B.1.1.7 in Switzerland