Date of Award

12-20-2024

Degree Type

Thesis

Degree Name

MPhil in Biological and Biomedical Sciences

First Advisor

Dr Sayed Ali Raza Shah Bukhari

Second Advisor

Prof. Dr. Zahra Hasan

Third Advisor

Dr. Javaria Ashraf

Department

Biological and Biomedical Sciences

Abstract

Background: The COVID-19 pandemic, caused by SARS-CoV-2, resulted in a global health and economic crisis with varying disease severity across populations. Emerging evidence suggests mitochondrial DNA (mtDNA) haplogroups and variants influence COVID-19 susceptibility and severity in host. This study explores the role of mtDNA responses in COVID-19.
Objective: To investigate mitochondrial haplogroups and mtDNA markers (variants) in Pakistani COVID[1]19 patients, aiming to identify host genetic factors associated with disease severity and understand changes in mitochondrial responses during infection. With a focus on the analysis of major variants, haplogroups and Global Private Mutations (GPM) and their role in disease severity.
Methods: A case-control study was conducted at The Aga Khan University Hospital, a tertiary care hospital in Karachi, Pakistan using mitochondrial DNA sequence data of samples from COVID[1]19 patients with varying disease severities, including mild (n=30), moderate (n=29) to critical/severe (n=28) infections.These were compared to mitochondrial genomes of healthy controls (n= 30). All samples were sequenced using the Illumina MiSeq platform. Bioinformatics-based analysis was used to identify variable genetic markers between study groups and with disease onset and severity. Statistical analysis was performed using GraphPad Prism 10, and a p-value of < 0.05 is considered significant.
Results: Our analysis identified population-specific mitochondrial variations, global private mutations, and haplogroups to be associated with COVID-19 onset and severity. Statistical significance was observed in the distribution of M haplogroup in the CS group with P value 0.0345. Other than that, haplogroup M was predominant in HC and AMD groups as well. Haplogroup U was also frequently observed specifically in the moderate group and is associated with moderate to high level of disease in our population. Mutation 5186T within MT-ND2 (NADH dehydrogenase 2) ,gene was the most prevalent in the MOD group while variant 13597A was present in CS deceased group and 310.1T in ATP6 was dominant in CS Alive group. Global Private Mutation 310.1C in control region of the mtDNA was prevalent in moderate group. However, in the mild and healthy control group, 310.1C in control region, 514d and 515d within COI (Cytochrome c Oxidase subunit I) gene and TL1 (tRNA Leucine 1) gene respectively were frequently observed suggesting these mutations has a protective influence on the disease severity.
Conclusions: Our findings enhance the understanding of the role of mtDNA in COVID-19 susceptibility and severity, potentially with the identification of at-risk populations. These insights can inform the development of targeted therapeutic strategies considering specific population and improve healthcare outcomes in COVID-19 infection

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