No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2

Abstract

COVID-19 is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised animal reservoir. Due to this recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any homoplasies observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we develop a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a curated set of recurrent mutations identified within a dataset of 46,723 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent mutations currently in circulation appear to be evolutionary neutral and primarily induced by the human immune system via RNA editing, rather than being signatures of adaptation. At this stage we find no evidence for significantly more transmissible lineages of SARS-CoV-2 due to recurrent mutations.

Epidemic trends of SARS-CoV-2 associated with immunity, race, and viral mutations

“…A global analysis of SARS-CoV-2 genomes reported that recurrent mutations did not increase the number of descendants, arguing against positive selection of mutants (22). However, as the present study has revealed, transmissible variants expand in niches that reflect population heterogeneity and avoidance of defensive herd immunity and viral competition.…”

“…However, as the present study has revealed, transmissible variants expand in niches that reflect population heterogeneity and avoidance of defensive herd immunity and viral competition. Therefore, even if the virus is highly transmissible, it cannot spread freely throughout the world, so a collective analysis of the world's subtypes (22) does not reveal a niche spread. Such context-sensitive propagation of the subtypes could only be visualized by scrutinizing the local spread.…”

“…Gene mutations continue to occur in the process of transmission from person to person because of the error-prone viral RNA polymerase and RNA editing (22). However, even if mutations continue to occur, they are not selected unless they cause amino acid changes that enhance virus transmission.…”

Epidemic trends of SARS-CoV-2 associated with immunity, race, and viral mutations

“…Gene mutations continue to occur in the process of transmission from person to person because of the error-prone viral FNA polymerase and RNA editing. 27 However, even if mutations continue to occur, they are not selected unless they are new protein changes that further increase the efficiency of virus transmission. As the mutation epidemic curve shows, the emergence of new mutations associated with virus spread have peaked out, strongly suggesting that there is little room for mutations to make more fit viruses.…”

Understanding the implications of SARS-CoV-2 re-infections on immune response milieu, laboratory tests and control measures against COVID-19

“…Second, coinfection of same host due to a recombination between two viral lineages may trigger genomic variability [ 20 ]. Third, mutations acquired through evolution can undergo induction by host RNA editing mechanisms which is associated with innate immune response [ 21 , 22 , 23 ]. Currently, there is no evidence that recurrent mutations in SARS-CoV-2 can lead to increased viral transmission.…”