Characterizing SARS-CoV-2 mutations in the United States

TL;DR

This study analyzes SARS-CoV-2 mutations in the US, revealing four main substrains, their origins, mutation groups, and gender-dependent mutation effects, highlighting increased infectivity and informing containment strategies.

Contribution

It introduces a comprehensive multi-method analysis of US SARS-CoV-2 mutations, identifying distinct substrains, mutation groups, and gender-related mutation effects not previously characterized.

Findings

US SARS-CoV-2 has four main substrains.

Five top mutations originated outside the US, three within the US.

Three US substrains are more infectious.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been mutating since it was first sequenced in early January 2020. The genetic variants have developed into a few distinct clusters with different properties. Since the United States (US) has the highest number of viral infected patients globally, it is essential to understand the US SARS-CoV-2. Using genotyping, sequence-alignment, time-evolution, $k$-means clustering, protein-folding stability, algebraic topology, and network theory, we reveal that the US SARS-CoV-2 has four substrains and five top US SARS-CoV-2 mutations were first detected in China (2 cases), Singapore (2 cases), and the United Kingdom (1 case). The next three top US SARS-CoV-2 mutations were first detected in the US. These eight top mutations belong to two disconnected groups. The first group consisting of 5 concurrent mutations is prevailing, while the other group with three concurrent mutations gradually fades out. Our analysis suggests that female immune systems are more active than those of males in responding to SARS-CoV-2 infections. We identify that one of the top mutations, 27964C$>$T-(S24L) on ORF8, has an unusually strong gender dependence. Based on the analysis of all mutations on the spike protein, we further uncover that three of four US SASR-CoV-2 substrains become more infectious. Our study calls for effective viral control and containing strategies in the US.