The Pathogen Genomics group in KAUST uses a combination of high-throughput sequencing, comparative and functional genomics protocols and bioinformatic analysis tools to study natural genomic alterations and pathogenicity determinants in selected parasitic protists, bacteria and viruses with significant impact on human and animal health. KAUST Smart Health Initiative (KSHI) is funding several of these projects. Our KSHI-funded projects cover a wide range of topics on Health and Wellness including genomic surveillance of endemic viruses, and metagenomics-driven discovery of pathogens and microbiomes in health and disease in Saudi Arabia. During my presentation, I shall be focusing on KSHI-funded projects on COVID-19 and Dengue in Saudi Arabia under the umbrella of the KSHI. In addition, I shall be presenting our recent and ongoing studies on the role of the Nucleocapsid protein mutations of the SARS-CoV-2 in COVID-19 severity. All these projects involve active collaborations with several healthcare institutions within the KSA and the Saudi MOH regional research laboratories.