Project Summary/Abstract Severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) has rapidly spread across the world. As of June, 2021, over 171 million laboratory-confirmed cases and greater than 3.68 million deaths have been reported globally. This increase in cases has been associated with emergence of new variants which have increased transmissibility and severity. While Southeast Asia kept COVID-19 cases under relative control in 2020. In 2021, SARS-CoV-2 began to spread rapidly and caused continuing outbreaks in the region. In Africa, the genomic surveillance gap, combined with very fragile health systems with limited management capacities, exposes the continent to possible new COVID-19 waves that could prove to be much more severe on the continent, where vaccination clearly remains at a very timid stage. The overall goal of the project is to increase sequencing capacity and add to the depth of sequencing knowledge available in South East Asia and African countries with 4 Specific Aims. 1)To increase sequencing numbers for samples from certain regions. We will focus on samples from land borders with Thailand and Vietnam and community transmission in Cambodia stemming from the February 20th ?event.? These sequences will help to understand community transmission within Cambodia. In Africa, we will increase sequencing numbers from samples from African countries with very low sequencing coverage including Mali, Burkina Faso, Guinea, Côte d?Ivoire, Guinea-Bissau, Niger, Cabo-Verde, Mauritania, Tunisia, Madagascar, Cameroon, Equatorial Guinea and Central Africa Republic. We will confirm known variants of concern as well as detection of potential local new variants. 2)To increase sequencing numbers for samples from patients with atypical profiles. We will systematically collect data at epidemiological level for demographical data, clinical symptoms, COVID-19 vaccination status, history of COVID-19 in relation with patients. We will focus on re-infected patient samples, severe COVID-19 cases and post-vaccinated SARS-CoV-2 infected patients. 3) To monitor introduction and dissemination of known VOCs using molecular sub-typing tools. We will help participating countries building up molecular capacities to subtype known variants. 4) Identify viral genetic determinants of high transmissibility and disease severity. Sequences from severe cases will be analyzed in comparison to the sequences from the randomly selected group to identify viral genetic signatures associated to disease severity. Regarding the transmissibility, we will rely on circulation dynamics of the detected variants in each country as well as in all countries. Overall, the studies outlined in this proposal will rapidly add essential sequence data needed regarding COVID-19 cases in lower?middle income, least-developed countries. They will provide the basis for further study on inter-/intra-host variant emergence and vaccine escape in a unique population from a least-developed country in an understudied, but vitally important, region of the world.