COVFlow: virus phylodynamics analyses from selected SARS-CoV-2 sequences

Phylodynamic analyses generate important and timely data to optimise public health response to SARS-CoV-2 outbreaks and epidemics. However, their implementation is hampered by the massive amount of sequence data and the difficulty to parameterise dedicated software packages. We introduce the COVFlow pipeline, accessible at https://gitlab.in2p3.fr/ete/CoV-flow, which allows a user to select sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database according to user-specified criteria, to perform basic phylogenetic analyses, and to produce an XML file to be run in the Beast2 software package. We illustrate the potential of this tool by studying two sets of sequences from the Delta variant in two French regions. This pipeline can facilitate the use of virus sequence data at the local level, for instance, to track the dynamics of a particular lineage or variant in a region of interest.

From Delta to Omicron: analysing the SARS-CoV-2 epidemic in France using variant-specific screening tests (September 1 to December 18, 2021)

We analysed 131,478 SARS-CoV-2 variant screening tests performed in France from September 1st to December 18, 2021. Tests consistent with the presence of the Omicron variant exhibit significantly higher cycle threshold Ct values, which could indicate lower amounts of virus genetic material. We estimate that the transmission advantage of the Omicron variant over the Delta variant is +105% (95% confidence interval: 96-114%). Based on these data, we use mechanistic mathematical modelling to explore scenarios for early 2022.

Spread of SARS-CoV-2 Delta variant infections bearing the S:E484Q and S:T95I mutations in July and August 2021 in France

Analysing 92,598 variant screening tests performed on SARS-CoV-2 positive samples collected in France between 1 July and 31 August 2021 shows an increase of Kappa-like infections. Full genome sequencing reveals that these correspond to Delta variants bearing the S:E484Q mutation. Most of these sequences belong to a phylogenetic cluster and also bear the S:T95I mutation. Further monitoring is needed to determine if this trend is driven by undocumented superspreading events or an early signal of future viral evolutionary dynamics.

Inferring SARS-CoV-2 variant within-host kinetics

Since early 2021, SARS-CoV-2 variants of concern (VOCs) have been causing epidemic rebounds in many countries. Their properties are well characterised at the epidemiological level but the potential underlying within-host determinants remain poorly understood. We analyse a longitudinal cohort of 6,944 individuals with 14,304 cycle threshold (Ct) values of qPCR VOC screening tests performed in the general population and hospitals in France between February 6 and August 21, 2021. To convert Ct values into numbers of virus copies, we performed an additional analysis using droplet digital PCR (ddPCR). We find that the number of viral genome copies reaches a higher peak value and has a slower decay rate in infections caused by Alpha variant compared to that caused by historical lineages. Following the evidence that viral genome copies in upper respiratory tract swabs are informative on contagiousness, we show that the kinetics of the Alpha variant translate into significantly higher transmission potentials, especially in older populations. Finally, comparing infections caused by the Alpha and Delta variants, we find no significant difference in the peak viral copy number. These results highlight that some of the differences between variants may be detected in virus load variations.

The SARS-CoV-2 B.1.351/V2 variant is outgrowing the B.1.1.7/V1 variant in French regions in April 2021

SARS-CoV-2 variants threaten our ability to control COVID-19 epidemics. We analyzed 36,590 variant-specific RT-PCR tests performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Contrarily to January to March 2021, we found that the V2 variant had a significant transmission advantage over V1 in some regions (15.1 to 16.1% in Ile-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of V2 and the high levels of immunization in these regions.

SARS-CoV-2 variants of concern are associated with lower RT-PCR amplification cycles between January and March 2021 in France

SARS-CoV-2 variants raise concern regarding the mortality caused by COVID-19 epidemics. We analyse 88,375 cycle amplification (Ct) values from variant-specific RT-PCR tests performed between January 26 and March 13, 2021. We estimate that on March 12, nearly 85% of the infections were caused by the V1 variant and that its transmission advantage over wild type strains was between 38 and 44%. We also find that tests positive for V1 and V2/V3 variants exhibit significantly lower cycle threshold (Ct) values.

Epidemiological and clinical insights from SARS-CoV-2 RT-PCR cycle amplification values

The SARS-CoV-2 pandemic has led to an unprecedented daily use of molecular RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of amplification cycles (Ct), is debated because of strong potential biases. We analyze a national database of tests performed on more than 2 million individuals between January and November 2020. Although we find Ct values to vary depending on the testing laboratory or the assay used, we detect strong significant trends with patient age, number of days after symptoms onset, or the state of the epidemic (the temporal reproduction number) at the time of the test. These results suggest that Ct values can be used to improve short-term predictions for epidemic surveillance.

Rapid SARS-CoV-2 variants spread detected in France using specific RT-PCR testing

SARS-CoV-2 variants raise major concerns regarding the control of COVID-19 epidemics. We analyse 40,000 specific RT-PCR tests performed on SARS-CoV-2-positive samples collected between Jan 26 and Feb 16, 2021. We find a high transmission advantage of variants and show that their spread in the country is more advanced than anticipated.