Variant-specific SARS-CoV-2 within-host kinetics

Abstract

Since early 2021, SARS-CoV-2 variants of concern (VOCs) have been causing epidemic rebounds in many countries. Their properties are well characterized at the epidemiological level but the potential underlying within-host determinants remain poorly understood. We analyze a longitudinal cohort of 6944 individuals with 14 304 cycle threshold (Ct) values of reverse-transcription quantitative polymerase chain reaction (RT-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.

Keywords: SARS-Cov2; ddPCR; variant of concern; viral dynamics; within-host.

Figure 1

Data set formatting steps. n indicates the number of tests, that is, Ct values, analyzed. For the IDS1 assay, the analyses were performed directly on the Ct values because the provider did not have any remaining tests to use with the ddPCR calibration. Furthermore, the assessment of the virus lineage (i.e., wild type or variants of concern) was only performed for tests with Ct values lower or equal than 30. For results obtained using the IDS2 and Perkin assays, Ct values were converted into viral genome copies before subsequent analysis and the assessment of the virus lineage was only performed for tests with more than 5.4log₁₀ copies/ml

Figure 2

Ct value as a function of SARS‐CoV2 copy number. The shape indicates the virus lineage and the color variant screening assay used to obtain the Ct value for the control probe targeting the N gene. Virus copy number was estimated using a droplet digital polymerase chain reaction targeting the N gene

Figure 3

Within‐host longitudinal Ct data as a function of the virus lineage. The dots represent the observed values. The bold dots represent the median value for each day and each strain. The lines represent the linear model for an average patient (median age, nonhospitalized). (A) Model with Ct values of historical lineages versus the Alpha variant. (B) Model of virus copies per milliliter of Alpha versus Delta variant. Both models were set approximately on the same scale on the y‐axis

Figure 4

Impact of the differential viral genome copies on the transmissibility. (A) Relationship between infectivity and Ct, after the viral genome copies peak, for the historical strain. (B) The linear model parameters were used, with the demography of each country, to infer the transmission advantage of the variants. The error bars represent the 95% bootstrap quantile