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The emergence of Variants of Concern (VOCs) of SARS-CoV-2 with increased transmissibility, immune evasion properties, and virulence poses a great challenge to public health. Despite unprecedented efforts to increase genomic surveillance, fundamental facts about the evolutionary origins of VOCs remain largely unknown. One major uncertainty is whether the VOCs evolved during transmission chains of many acute infections or during long-term infections within single individuals. We test the consistency of these two possible paths with the observed dynamics, focusing on the clustered emergence of the first three VOCs, Alpha, Beta, and Gamma, in late 2020, following a period of relative evolutionary stasis. We consider a range of possible fitness landscapes, in which the VOC phenotypes could be the result of single mutations, multiple mutations that each contribute additively to increasing viral fitness, or epistatic interactions among multiple mutations that do not individually increase viral fitness—a “fitness plateau”. Our results suggest that the timing and dynamics of the VOC emergence, together with the observed number of mutations in VOC lineages, are in best agreement with the VOC phenotype requiring multiple mutations and VOCs having evolved within single individuals with long-term infections.
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This content will become publicly available on April 21, 2026
A data‐driven sliding‐window pairwise comparative approach for the estimation of transmission fitness of SARS‐CoV‐2 variants and construction of the evolution fitness landscape
Estimating the transmission fitness of SARS‐CoV‐2 variants and understanding their evolutionary fitness trends are important for epidemiological forecasting. Existing methods are often constrained by their parametric natures and do not satisfactorily align with the observations during COVID‐19. Here, we introduce a sliding‐window data‐driven pairwise comparison method, the differential population growth rate (DPGR) that uses viral strains as internal controls to mitigate sampling biases. DPGR is applicable in time windows in which the logarithmic ratio of two variant subpopulations is approximately linear. We apply DPGR to genomic surveillance data and focus on variants of concern (VOCs) in multiple countries and regions. We found that the log‐linear assumption of DPGR can be reliably found within appropriate time windows in many areas. We show that DPGR estimates of VOCs align well with regional empirical observations in different countries. We show that DPGR estimates agree with another method for estimating pathogenic transmission. Furthermore, DPGR allowed us to construct viral relative fitness landscapes that capture the shifting trends of SARS‐CoV‐2 evolution, reflecting the relative changes of transmission traits for key genotypic changes represented by major variants. The straightforward log‐linear regression approach of DPGR may also facilitate its easy adoption. This study shows that DPGR is a promising new tool in our repertoire for addressing future pandemics.
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- PAR ID:
- 10587106
- Publisher / Repository:
- WILEY
- Date Published:
- Journal Name:
- Quantitative Biology
- Volume:
- 13
- Issue:
- 4
- ISSN:
- 2095-4689
- Subject(s) / Keyword(s):
- viral pathogen, fitness
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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