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020 _aTHE0010437 (Local)
_qHardback
040 _aUMPSA
_beng
_cUMPSA
_erda
090 _aFIST .U46 2025 r Thesis
100 1 _aUmmu Afeera Binti Zainulabid,
_eauthor.
245 1 0 _aSars-cov-2 genomic surveillance in pahang, malaysia
_b: a two-year window on the pandemic (december 2019 to november 2021) /
_cUmmu Afeera Binti Zainulabid
264 1 _aKuantan, Pahang :
_bUMPSA,
_c2025
264 4 _c© 2025
300 _axxviii, 336 pages :
_billustrations (some color)
_c30 cm. +
_e1 CD-ROM
336 _2rdacontent
_atext
337 _2rdamedia
_aunmediated
338 _2rdacarrier
_avolume
347 _2rda
_atext file
_bPDF
500 _aFaculty of Industrial Sciences and Technology
502 _aInclude bibliographical reference
504 _aThe 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.
610 2 0 _aFaculty of Industrial Sciences and Technology
_xDissertations
650 0 _aUniversities and colleges
_xDissertations
650 0 _aTheses
_xDissertations
942 _2lcc
_cTHESIS
999 _c104636
_d104642