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Background: Following the COVID-19 pandemic declaration, the World Health Organization recommended suspending neglected tropical diseases (NTD) control activities as part of sweeping strategies to minimise COVID-19 transmission. Understanding how NTD programs were impacted and resumed operations will inform contingency planning for future emergencies. This is the first study that documents how South-East Asian and Pacific NTD programs addressed challenges experienced during the COVID-19 pandemic. Methodology/Principal findings: Data was collected through semi-structured interviews with 11 NTD Program Coordinators and related personnel from Fiji, Papua New Guinea, The Philippines, Timor-Leste, and Vanuatu. Constructivist grounded theory methods were drawn on to generate an explanation of factors that enabled or hindered NTD program operations during the COVID-19 pandemic. The COVID-19 pandemic disrupted NTD programs in all countries. Some programs implemented novel strategies by partnering with services deemed essential or used new communications technology to continue (albeit scaled-back) NTD activities. Strong relationships to initiate cross-program integration, sufficient resources to implement adapted activities, and dedicated administrative systems were key enabling factors for recommencement. As the COVID-19 pandemic continued, exacerbating health resources scarcity, programs faced funding shortages and participants needed to find efficiencies through greater integration and activity prioritisation within their NTD units. Emphasising community-led approaches to restore trust and engagement was critical after widespread social anxiety and disconnection. Conclusions/Significance: Sustaining effective NTD programs during a global emergency goes beyond managing immediate activity disruptions and requires attention to how NTD programs can be better ensconced within wider health programs, administrative, and social systems. This study underscores the importance of pre-emergency planning that reinforces NTD control programs as a critical service at all health systems levels, accompanied by governance arrangements that increase NTD staff control over their operations and strategies to maintain strong community relationships. Ensuring NTD units are supported via appropriate funding, personnel, and bureaucratic resources is also required. Author summary: Disruptions to health services during the COVID-19 pandemic may delay progress in neglected tropical diseases (NTDs) control by several years. Current studies of how NTD programs responded to the challenges arising from the COVID-19 pandemic are largely from African settings and focus on earlier periods during the pandemic when policy advice was most stringent. In contrast, this study documents how NTD staff and other related personnel in five South-East Asian and Pacific countries adapted to changing situations throughout the pandemic. We found a difference in the strategies NTD programs initially used to manage the immediate challenges of strict new public health measures compared to those used later in the pandemic's evolution when seeking to recommence usual programs. Initially, some NTD programs devised new ways of offering modified services, primarily though cross-program integration with other health services that were allowed to continue operating. When operations re-commenced, NTD programs faced financial challenges that meant human and resource efficiencies in these units needed to be found. The cumulative impact of pandemic-related restrictions and misinformation eroded community trust in health programs more broadly and required NTD staff to rebuild local relationships. The lessons learned in these settings may help NTD programs in these and other regions prepare for prolonged future emergencies. [ABSTRACT FROM AUTHOR]