Introduction For patients at high risk of severe COVID-19 disease, antiviral therapeutic options are available to reduce the risk of hospitalization or death. Although many countries have developed national guidelines for COVID-19 management that include use of antiviral agents, it is unclear how these guidelines are used in daily clinical practice. This study aims to assess the management of high-risk COVID-19 patients in the Middle East, Africa, and Eastern Europe, with a focus on understanding current practices, challenges, and potential strategies for improvement. Methods Healthcare professionals (HCPs) from the Middle East, Africa, and Eastern Europe came together at a regional summit in February 2023 to share perspectives on the therapeutic management of patients at high risk of serious COVID-19 disease in the community. Summit participants represented diverse medical specialties, geographical regions, and healthcare settings. Key insights gathered during the summit were supplemented with evidence from the published literature via a non-systematic literature search of MEDLINE and online sources such as government reports since the start of 2020 to identify articles on disease burden, unmet needs, treatment access, antiviral therapy, guidelines related to individuals with COVID-19 at high-risk for poor outcomes in low- and middle-income countries (LMICs). Together, these sources were used by the authors to generate their recommendations for future priorities and optimal care pathways globally. Results Specific insights gathered from the summit were that participants reported that primary care is the first point of contact for high-risk patients, but the role of primary care physicians (PCPs) in treatment is uncertain. Additionally, participants highlighted that between-country differences in the care pathway for high-risk patients are due to variations in local treatment practices, healthcare system structures, and resourcing. In line with the published literature, participants agreed that HCP education is needed to support the identification, counseling, and appropriate management of high-risk patients and that pharmacists have a critical role to play in identifying clinically important potential interactions with antiviral treatment and recommending appropriate adjustments. Furthermore, patient hesitancy can result in late presentation, delayed treatment, and potential progression of symptoms. HCPs should proactively counsel high-risk patients, so they are aware of their risk and its implications and understand what to do if they experience symptoms of COVID-19. Targeted educational initiatives for patients are needed to mitigate reluctance to undergo COVID-19 testing and counter COVID-19 misinformation. Conclusion Collaboration among stakeholders is essential to optimize COVID-19 management for high-risk patients globally, ensuring effective implementation of guidelines and improving outcomes.