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Host Immune Response Driving SARS-CoV-2 Evolution
Rui Wang1, Yuta Hozumi1, Yong-Hui Zheng2
1Department of Mathematics, Michigan State University, East Lansing, MI 48824, USA.
Abstract:
The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance in controlling and combating the coronavirus disease 2019 (COVID-19) pandemic. Currently, over 15,000 SARS-CoV-2 single mutations have been recorded, which have a great impact on the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2's 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 overreaction 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 COVID-19 infection 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.
Insights
Host immune responses, specifically APOBEC and ADAR gene editing, drive most SARS-CoV-2 mutations. Viral evolution trends and high-risk populations for COVID-19 were also identified.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- The transmission and evolution of SARS-CoV-2 are critical for managing the COVID-19 pandemic.
- Over 15,000 SARS-CoV-2 mutations have been documented, impacting diagnostics, vaccines, and therapeutics.
- Limited understanding exists regarding SARS-CoV-2 evolutionary patterns.
Purpose of the Study:
- To conduct a comprehensive genotyping analysis of SARS-CoV-2 mutations.
- To identify the primary drivers of viral mutations.
- To investigate demographic and geographic variations in COVID-19 severity and viral evolution.
Main Methods:
- Comprehensive genotyping analysis of existing SARS-CoV-2 mutations.
- Analysis of mutation types and their correlation with host immune responses (APOBEC, ADAR).
- Comparative analysis of population responses across different continents and age groups.
Main Results:
- Host immune responses, via APOBEC and ADAR gene editing, account for approximately 65% of recorded SARS-CoV-2 mutations.
- Children under five and the elderly may face higher COVID-19 risks due to exaggerated immune responses.
- Populations in Oceania and Africa exhibit more intense reactions to SARS-CoV-2 infection compared to Europe and Asia.
- The ratio of C > T to T > C mutations can predict the evolutionary order of related viral sequences.
Conclusions:
- Host APOBEC and ADAR gene editing are major contributors to SARS-CoV-2 genetic diversity.
- Specific age groups and geographic populations display differential susceptibility and immune responses to SARS-CoV-2.
- Mutation type ratios offer insights into viral evolutionary trajectories.
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