04692nam a2200325 i 4500 MY-KuUP 20260406175835.0 t||||fr|||| 000 0 ta 260406t20252025my a|||fr|||| 000 0 eng d THE0010437 (Local) Hardback UMPSA eng UMPSA rda FIST .U46 2025 r Thesis Ummu Afeera Binti Zainulabid, author. Sars-cov-2 genomic surveillance in pahang, malaysia : a two-year window on the pandemic (december 2019 to november 2021) / Ummu Afeera Binti Zainulabid Kuantan, Pahang : UMPSA, 2025 © 2025 xxviii, 336 pages : illustrations (some color) 30 cm. + 1 CD-ROM rdacontent text rdamedia unmediated rdacarrier volume rda text file PDF Faculty of Industrial Sciences and Technology Include bibliographical reference The COVID-19 pandemic, driven by the novel coronavirus, SARS-CoV-2, has presented unparalleled challenges to global public health. There is limited understanding of the genomic dynamics and epidemiology of the virus during the early outbreak, hindering effective control and mitigation efforts. The objectives of this study are to develop an effective approach to enhance SARS-CoV-2 genome sequencing quality, elucidate the impact of genomic mutation among local variants, and investigate the role of sequencing in clinical application. This study presents findings from a comprehensive investigation into the genomic landscape and transmission patterns of SARS-CoV-2 within the local context of Pahang, Malaysia, from December 2019 to November 2021. Utilizing innovative hybrid sequencing methods via de novo assembly and annotation approaches, we conducted one of the earliest genomic studies of SARS-CoV-2 in Malaysia, providing valuable insights into viral evolution and variant dynamics. Our analysis identified the emergence of the D614G mutation as early as March to May 2020, preceding official reports by the Ministry of Health. This mutation is predicted to increase both the stability and molecular flexibility of the Pahang/IIUM91 S protein based on computational analysis using DynaMut. Additionally, we studied the impact of key variants of concern among 1,356 individuals infected with SAR-CoV-2, including Beta and Delta, along with locally circulating variants B.1.524 and AU.2, on the epidemiology of COVID-19 in the region. Notably, we discovered a unique mutation at G1223C exclusively in Pahang SARSCoV- 2 D614G variants. This mutation is underreported and warrants further investigation. Furthermore, the N439K mutation observed in the Receptor-Binding Domain (RBD) of AU.2 deserves additional attention and monitoring due to its potential to increase virus infectivity while evading antibody-mediated immunity. In addition to genomic analysis, we employed network analysis for outbreak investigation, identifying "superspreaders" and mitigating hospital outbreaks, facilitating the selection of representative samples for sequencing in resource-limited settings. This approach enhanced our understanding of local transmission dynamics and guided targeted public health interventions during the outbreak and in the near future. Furthermore, our study revealed rare clinical manifestations of SARS-CoV-2, such as acquired hemophilia and AVNRT related to specific mutations in NSP3 and C3037T, respectively, highlighting the diverse clinical spectrum of the disease. Despite the strengths of our study, including pioneering genomic SARS-CoV-2 research in Malaysia and innovative methodological approaches, several limitations were identified. These include constraints related to sample size and available resources, highlighting the ongoing need for investment in sequencing infrastructure and capacity-building initiatives. In conclusion, this study provides valuable insights into the genomic dynamics and epidemiology of SARS-CoV-2 in Pahang, Malaysia. Our findings contribute to the global understanding of COVID-19 and emphasize the significance of interdisciplinary collaboration, data sharing, and community engagement in addressing public health challenges. Moving forward, concerted efforts are needed to strengthen genomic surveillance, enhance research capabilities, and implement evidence-based interventions to control the spread of the virus and mitigate its impact on society. Faculty of Industrial Sciences and Technology Dissertations Universities and colleges Dissertations Theses Dissertations lcc THESIS 0 0 lcc 0 0 10000 10000 2026-04-06 0 FIST .U46 2025 r Thesis T000004762 2026-04-06 17:59:27 2026-04-06 THESIS 0 0 lcc 0 0 10000 10000 2026-04-06 0 CD13982 T000004763 2026-04-06 18:00:15 2026-04-06 THESIS 104636 104642