The Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) was a novel network of networks created in response to the COVID-19 pandemic. This program brought together a large matrix of clinical research networks to swiftly design and/or implement concurrent clinical studies. Successful coordination of this large-scale collaboration required innovative solutions for timely and transparent centralized operations reporting. As the Administrative Coordinating Center (ACC) for CONNECTS, RTI International developed and maintained a web-based infrastructure that served as the central communication and reporting hub. This single-platform approach provided a robust collection of key topics to support daily operational oversight (e.g., enrollment and retention, site coverage, study milestones, financial tracking). Underlying data acquisition, harmonization, and portal reporting methods aimed to address nuances of the network of networks (e.g., disparate data sources, diverse user needs) while providing the necessary speed and agility to combat the COVID-19 pandemic. The resulting system was well received, readily adapted to changes, and successfully supported three years of early COVID-19 research. Although the CONNECTS central reporting methods arose from necessity during an urgent and dynamic public health emergency, they are a model for efficient and effective centralized operational reporting for any large-scale public health research effort.