This paper contributes to a better understanding of a system of pandemic knowledge exchanges. Therefore, three different case studies conducted in Germany, Greece, and Turkiye and executed in multiple countries were analyzed in the context of Mode 3 knowledge production and the Quintuple Helix system. While the Quintuple Helix system describes the knowledge exchange processes between the systems of science, economy, politics, public, and natural environment of societies for sustainable innovation processes, Mode 3 emphasizes the importance of a creative environment for research and innovation. The COVID-19 pandemic revealed that the need for knowledge exchange with the media-based public increased dramatically. In both models, Mode 3 and the Quintuple Helix but also in the Design Thinking approach, the creative environment incorporates the knowledge of the media-based public. Nonetheless, the reality of the public is constructed as media reality. Therefore, a mix of evidence-based and opinion-based knowledge is produced and transferred during knowledge exchange in the context of innovation processes including public engagement. It could be understood that the mediating entities media and general practitioners have a similar double function in the context of knowledge exchange with the public during the pandemic times. The results reveal the big need for knowledge communication and exchange platforms which on the one hand strengthen citizen participation by transforming opinion-based into evidence-based content. On the other hand, reach the status of a global standard medium for the pandemic knowledge exchange accepted by all stakeholders of the Quintuple Helix. This generates a shared-knowledge environment with a gain for all systems of the Quintuple Helix during the sustainable innovation processes.