MS Thesis Defense | SARS-CoV-2 Intra-host Evolution In Immunocompromised Patients for the Emergence of Variants of Concerns by Azari Ibrahim Bantan

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Building 3, Level 5, Conference Room 5209


Unexpected high mutations detected in new emerging variants of concern (VOCs) of 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in the case of 
omicron, raises concerns and efforts to understand their evolutionary trajectory. Several 
hypotheses have been discussed in literature to conceptualize the source of their 
emergence, including intra-host viral evolution in immunocompromised patients. These 
high-risk hosts are immune vulnerable, thus grant opportunities for the emergence of 
new variants through a persisting virus winning against host immunity, and selection for 
viral mutations driven by treatment interventions. Not many studies have investigated 
the evolutionary rate of SARS-CoV-2 in immunocompromised candidates. Therefore, the 
purpose of this study is to reveal the potential mechanisms underlying the emergence of 
VOCs by exploring substitution rate of SARS-CoV-2 genomes from surveyed COVID-19 
immunocompromised patients’ studies. First, SARS-CoV-2 genome sequences were 
collected at sequential time series throughout host infection, which were reported in the 
previous studies. Then, phylogenetic analysis was initially conducted followed by 
mutation rate analysis using two substantial similar approaches to calculate the rate in i) 
substitutions per month and ii) substitutions per site (per year). The mutation tendency 
of SARS-CoV-2 in immunocompromised hosts was compared to reported VOCs, 
particularly to omicron. Most patients showed significant high mutation rate due to 
prolonged infection and selection pressure by treatment interventions (i.e., convalescent 
plasma and antibodies). However, it is important to note the diverse evolutionary rate 
across the patients, probably due to the variation in sampling time points and various 
treatments regimes. Here, higher rate of intra-host viral evolution is detected in 
immunocompromised patients, which potentially lead to the emergence of VOC. This 
research highlights the need for sequencing efforts in high-risk individuals, updating 
treatment strategies along with further analysis on adaptive mutants pronounced as a 
result of intra-host evolution. Together, such findings provide an ultimate synergy for 
future public health guidelines and infection control measures.


Azari has received her BSc degree in Medical Genetics from the Medical School at 
Swansea University, UK, in 2020. There, she has experienced working in the immunology 
research department to discover host-dependent microenvironment in shaping the 
innate metabolic immune response upon elevated fructose exposure associated with 
cancer and infectious diseases. Soon after, she was admitted at KAUST for M.S. in 
Bioscience and joined the Computational Bioscience Research Center (CBRC) to conduct 
her master’s thesis. Currently, her bioinformatics research, supervised by Prof. Takashi 
Gojobori, is focused on understanding the evolutionary rate of SARS-CoV-2 in 
immunocompromised patients.

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