Abstract Objective Integrating clinical research into routine clinical care workflows within electronic health record systems (EHRs) can be challenging, expensive, and labor-intensive. This case study presents a large-scale clinical research project conducted entirely within a commercial EHR during the COVID-19 pandemic. Case Report The UCSD and UCSDH COVID-19 NeutraliZing Antibody Project (ZAP) aimed to evaluate antibody levels to SARS-CoV-2 virus in a large population at an academic medical center and examine the association between antibody levels and subsequent infection diagnosis. Results The project rapidly and successfully enrolled and consented over two thousand participants, integrating the research trial with standing COVID-19 testing operations, staff, lab, and mobile applications. EHR-integration increased enrollment, ease of scheduling, survey distribution and return of research results at a low cost by utilizing existing resources. Conclusion The case study highlights the potential benefits of EHR-integrated clinical research, expanding their reach across multiple health systems and facilitating rapid learning during a global health crisis.