With an alarmingly high rate of Long COVID, it is essential to address the lack of understanding of the pathogenesis and susceptibility to Long COVID. This study aims to investigate how symptoms and immunological markers of Long COVID are correlated in order to develop better biomarkers and inform strategies to accurately identify patients at high risk for developing Long COVID. It has been found that underlying health conditions increase the likelihood of developing Long COVID. Additionally, certain symptoms during COVID-19 infection have been linked to Long COVID. However, the immune system activity has not been well investigated for its correlation to the susceptibility and severity of Long COVID symptoms. In our study, human subjects from the United States and United Kingdom will be followed for a year, where they will be tested weekly for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), draw blood for immune system activity analysis, and report symptoms bidaily. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) will be used to detect and quantify the presence of SARS-CoV-2. Qualitative information about participants will be collected via the ZOE Health Study app to enable the collection of clinical metadata such as symptoms. This study’s unique and sizeable prospective cohort will provide critical knowledge about the susceptibility of patients to Long COVID by pre-existing symptomatology and immune markers. Moreover, we will better understand the possible mechanisms and pathogenesis of the disease.