Selection for infectivity profiles in slow and fast epidemics, and the rise of SARS-CoV-2 variants
- Collège de France, France
- Institut Pasteur, UMR2000, CNRS, France
- The University of Hong Kong, China
- Sorbonne Université, France
- Institut Pasteur, France
Abstract
Evaluating the characteristics of emerging SARS-CoV-2 variants of concern is essential to inform pandemic risk assessment. A variant may grow faster if it produces a larger number of secondary infections ('R advantage') or if the timing of secondary infections (generation time) is better. So far, assessments have largely focused on deriving the R advantage assuming the generation time was unchanged. Yet, knowledge of both is needed to anticipate impact. Here we develop an analytical framework to investigate the contribution of both the R advantage and generation time to the growth advantage of a variant. It is known that selection on a variant with larger R increases with levels of transmission in the community. We additionally show that variants conferring earlier transmission are more strongly favoured when the historical strains have fast epidemic growth, while variants conferring later transmission are more strongly favoured when historical strains have slow or negative growth. We develop these conceptual insights into a new statistical framework to infer both the R advantage and generation time of a variant. On simulated data, our framework correctly estimates both parameters when it covers time periods characterized by different epidemiological contexts. Applied to data for the Alpha and Delta variants in England and in Europe, we find that Alpha confers a +54% [95% CI, 45-63%] R advantage compared to previous strains, and Delta +140% [98-182%] compared to Alpha, and mean generation times are similar to historical strains for both variants. This work helps interpret variant frequency dynamics and will strengthen risk assessment for future variants of concern.
Data availability
The codes used for the analyses are available at https://github.com/FrancoisBlanquart/selection_variantThe data used for the analysis is previously available data that is publicly available. A cleaned version of the data used for the analysis is also available herehttps://github.com/FrancoisBlanquart/selection_variant
Article and author information
Author details
François Blanquart
Benjamin John Cowling
Funding
Centre National de la Recherche Scientifique (Momentum to FB)
- François Blanquart
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ben S Cooper, Mahidol University, Thailand
Publication history
- Received: November 23, 2021
- Preprint posted: December 9, 2021 (view preprint)
- Accepted: May 8, 2022
- Accepted Manuscript published: May 19, 2022 (version 1)
- Version of Record published: June 17, 2022 (version 2)
- Version of Record updated: June 28, 2022 (version 3)
Copyright
© 2022, Blanquart et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Selection for infectivity profiles in slow and fast epidemics, and the rise of SARS-CoV-2 variants
eLife 11:e75791.
https://doi.org/10.7554/eLife.75791
Further reading
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- Epidemiology and Global Health
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have been key drivers of new coronavirus disease 2019 (COVID-19) pandemic waves. To better understand variant epidemiologic characteristics, here we apply a model-inference system to reconstruct SARS-CoV-2 transmission dynamics in South Africa, a country that has experienced three VOC pandemic waves (i.e. Beta, Delta, and Omicron BA.1) by February 2022. We estimate key epidemiologic quantities in each of the nine South African provinces during March 2020 to February 2022, while accounting for changing detection rates, infection seasonality, nonpharmaceutical interventions, and vaccination. Model validation shows that estimated underlying infection rates and key parameters (e.g. infection-detection rate and infection-fatality risk) are in line with independent epidemiological data and investigations. In addition, retrospective predictions capture pandemic trajectories beyond the model training period. These detailed, validated model-inference estimates thus enable quantification of both the immune erosion potential and transmissibility of three major SARS-CoV-2 VOCs, that is, Beta, Delta, and Omicron BA.1. These findings help elucidate changing COVID-19 dynamics and inform future public health planning.
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- Epidemiology and Global Health
Background:
Vitamin D supplements are widely prescribed to help reduce disease risk. However, this strategy is based on findings using conventional epidemiological methods which are prone to confounding and reverse causation.
Methods:
In this short report, we leveraged genetic variants which differentially influence body size during childhood and adulthood within a multivariable Mendelian randomization (MR) framework, allowing us to separate the genetically predicted effects of adiposity at these two timepoints in the lifecourse.
Results:
Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), there was strong evidence that higher childhood body size has a direct effect on lower vitamin D levels in early life (mean age: 9.9 years, range = 8.9–11.5 years) after accounting for the effect of the adult body size genetic score (beta = −0.32, 95% CI = −0.54 to –0.10, p=0.004). Conversely, we found evidence that the effect of childhood body size on vitamin D levels in midlife (mean age: 56.5 years, range = 40–69 years) is putatively mediated along the causal pathway involving adulthood adiposity (beta = −0.17, 95% CI = −0.21 to –0.13, p=4.6 × 10-17).
Conclusions:
Our findings have important implications in terms of the causal influence of vitamin D deficiency on disease risk. Furthermore, they serve as a compelling proof of concept that the timepoints across the lifecourse at which exposures and outcomes are measured can meaningfully impact overall conclusions drawn by MR studies.
Funding:
This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/1).
