Saudi Cultural Missions Theses & Dissertations
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Item Restricted Investigating the impact of coronavirus infections on the host respiratory microbiome(University of Liverpool, 2024-05) Alrezaihi, Abdulrahman; Hiscox, JulianCoronaviruses, including the recent SARS-CoV-2, present a complex challenge for public health due to their ability to cause illnesses ranging from asymptomatic infection to patients suffering severe symptoms and death. This thesis employed advanced sequencing methods to identify and study different coronaviruses, from seasonal varieties to MERS-CoV and SARS- CoV-2, and their interactions with the host microbiome in both human clinical samples and animal models. This was underpinned by Oxford Nanopore long-read sequencing combined with modifications of sequence-independent single primer amplification (SISPA). This research aims were to improve the ability to detect coronaviruses, particularly in samples with low viral loads, by modifying different enrichment methods that were designed to detect SARS-CoV-2, identify lineages, and simultaneously define the nasal microbiome. The study revealed changes in the microbiome of patients with coronavirus infections, showing how the virus and the nasal microbiome interact. The data indicated that certain bacterial populations were more predominant in specific groups of patients with COVID-19 or MERS, potentially affecting the course of their illness. The investigation showed that dysbiosis, or microbial imbalance, was significant within coronavirus infections and occurred irrespective of the virus type (MERS-CoV or SARS-CoV-2) and mortality outcome. The investigation compared these patterns in human patients with those observed in a mouse model of SARS-CoV-2 that recapitulated severe disease. This study specifically identified differences in the microbiome between the upper and lower respiratory tracts. Examining the lower respiratory tract in humans is not common as this involves invasive sampling, and use of samples from intensive care patients facilitated this research. This comparison clarified how SARS- CoV-2 affected various parts of the respiratory system and showed that changes in viral load affected the microbiome composition within these distinct areas. Furthermore, the study defined how the microbiome changed throughout the infection, particularly in patients with severe illness who required intensive care.38 0