Early Cryptic Transmission and Evolution of SARS-CoV-2 in Human Hosts

 

Libing Shen

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Funan He

Fudan University - School of Life Sciences

DOI: https://dx.doi.org/10.2139/ssrn.3724275

PDF: https://papers.ssrn.com/sol3/Delivery.cfm/e6ec762e-683f-4fd6-838e-06fbbff4e222-MECA.pdf?abstractid=3724275&mirid=1&type=2

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is first identified in Wuhan City at the end of December 2019 and responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. So far this pandemic has claimed more than one million lives all over the world and its origin is still unknown.

Methods: In this study, we developed a method to search the least mutated strain using SARS-CoV-2 whole genome sequences. By parsimony principle, the least mutated strain should be the phylogenetic root for all SARS-CoV-2s. We further investigated the SARS-CoV-2’s adaptive evolutionary process in human hosts using the least mutated strain as the phylogenetic root and analyzed its strain diversity in different countries/regions.

Findings: According to their coding region identity, we classified 4571 SARS-CoV-2 genome sequences into 2449 viral strains collected from human hosts between December 2019 and July 2020. We found that the SARS-CoV-2 (NC_045512) strain first identified in Wuhan is not the least mutated strain. There are 41 SARS-CoV-2 strains harboring fewer global point mutations than the NC_045512 strain in our dataset. The least mutated strain can be found in eight countries across four continents due to SARS-CoV-2’s low mutability. Eight positive selection sites are identified in five SARS-CoV-2’s genes and four of them were present in the early stage of SARS-CoV-2’s human-to-human transmission. The NC_045512 strain has two positive selection sites, one in RNA-dependent RNA polymerase (L314P) and the other in spike protein (G614D). The statistical analysis of the SARS-CoV-2’s strain diversity in different countries/regions shows that the Indian subcontinent has the highest strain diversity. Furthermore, based on the SARS-CoV-2’s mutation rate, we estimate that the earliest SARS-CoV-2 transmission in human hosts could be traced back to July or August of 2019.

Interpretation: Our result shows that Wuhan is not the place where human-to-human SARS-CoV-2 transmission first happened. Before it spread to Wuhan, SARS-CoV-2 has already experienced adaptive evolution during its human-to-human transmission. The positive selection sites could contribute to the different clinical features of different SARS-CoV-2 strains. Both the least mutated strain’s geographic information and the strain diversity suggest that the Indian subcontinent might be the place where the earliest human-to-human SARS-CoV-2 transmission occurred, which was three or four months prior to the Wuhan outbreak. Our study helps to elucidate the early cryptic transmission and evolution of SARS-CoV-2 in human hosts and provide the new thinking for the global management of the COVID-19 pandemic.

Funding Statement: None to declare.

Declaration of Interests: None to declare.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3724275