Host immune response driving SARS-CoV-2 evolution

TL;DR

This study analyzes SARS-CoV-2 mutations, revealing host immune responses as a primary mutation driver, and highlights demographic and geographic factors influencing infection severity and mutation patterns.

Contribution

It provides a comprehensive genotyping analysis linking host immune mechanisms to mutation patterns and demographic factors affecting COVID-19 risk and viral evolution.

Findings

Host immune response via APOBEC and ADAR causes 65% of mutations.

Children under five and the elderly may have higher COVID-19 risk.

Population differences influence immune response and mutation patterns.

Abstract

The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance to the controlling and combating of coronavirus disease 2019 (COVID-19) pandemic. Currently, near 15,000 SARS-CoV-2 single mutations have been recorded, having a great ramification to the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2 evolutionary characteristics and general trend. In this work, we present a comprehensive genotyping analysis of existing SARS-CoV-2 mutations. We reveal that host immune response via APOBEC and ADAR gene editing gives rise to near 65\% of recorded mutations. Additionally, we show that children under age five and the elderly may be at high risk from COVID-19 because of their overreacting to the viral infection. Moreover, we uncover that populations of Oceania and Africa react significantly more intensively to SARS-CoV-2 infection than those of Europe and Asia, which may explain why African Americans were shown to be at increased risk of dying from COVID-19, in addition to their high risk of getting sick from COVID-19 caused by systemic health and social inequities. Finally, our study indicates that for two viral genome sequences of the same origin, their evolution order may be determined from the ratio of mutation type C$>$T over T$>$C.