Decomposing the sources of SARS-CoV-2 fitness variation in the United States

Abstract

The fitness of a pathogen is a composite phenotype determined by many different factors influencing growth rates both within and between hosts. Determining what factors shape fitness at the host population-level is especially challenging because both intrinsic factors like pathogen genetics and extrinsic factors such as host behavior influence between-host transmission potential. This challenge has been highlighted by controversy surrounding the population-level fitness effects of mutations in the SARS-CoV-2 genome and their relative importance when compared against non-genetic factors shaping transmission dynamics. Building upon phylodynamic birth–death models, we develop a new framework to learn how hundreds of genetic and non-genetic factors have shaped the fitness of SARS-CoV-2. We estimate the fitness effects of all amino acid variants and several structural variants that have circulated in the United States between February 2020 and March 2021 from viral phylogenies. We also estimate how much fitness variation among pathogen lineages is attributable to genetic versus non-genetic factors such as spatial heterogeneity in transmission rates. Before September 2020, most fitness variation between lineages can be explained by background spatial heterogeneity in transmission rates across geographic regions. Starting in late 2020, genetic variation in fitness increased dramatically with the emergence of several new lineages including B.1.1.7, B.1.427, B.1.429 and B.1.526. Our analysis also indicates that genetic variants in less well-explored genomic regions outside of Spike may be contributing significantly to overall fitness variation in the viral population.

Phylogenetic and phylodynamic approaches to understanding and combating the early SARS-CoV-2 pandemic

“… A selection of studies providing phylodynamic estimates of both growth and clock rates are listed; other studies have published estimates of clock rates 79 , 122 or reproduction numbers 30 , 32 , 81 , 137 , 138 . Confidence intervals are provided where available (95% highest posterior density (HPD)).…”

The first three waves of the Covid-19 pandemic hint at a limited genetic repertoire for SARS-CoV-2

“… 2021 ). Nevertheless, it was estimated that the fitness benefit of these two mutations in combination was very minor, when comparing pre-September 2020 US data with later data (Kepler, Hamins-Puertolas and Rsmussen 2021 ). These authors speculate that their counter-intuitive finding may be due to genetic backgrounds in which these mutations were found, but by September 2020 Janus was already on the rise (Fig.…”

Evasion of Vaccine-Induced Humoral Immunity by Emerging Sub-Variants of SARS-CoV-2

“…Another question is why Beta+R346K did not proliferate despite its immune-escaping capacity. Kepler et al decomposed the fitness of pathogens into intrinsic factors such as viral genetics and extrinsic factors such as climate and host factors [ 25 ]. Unlike the Alpha and the Delta variants, proliferation of the Beta variant was quite limited.…”