Abstract Text: Borrelia burgdorferi is a bacterial spirochete that causes Lyme disease (LD). Patients with LD exhibit a high degree of variability in clinical presentation and disease severity, suggesting individual immune responses may drive this heterogeneity. Unfortunately, even after receiving a correct diagnosis and standard of care antibiotic treatment, approximately 10% of people will experience persistent symptoms. This is similar to observations with Long COVID, which has significant overlap in symptom presentation as chronic LD. Currently, there are no known biomarkers that can distinguish between acute and chronic LD, or predict which acute LD patients will return to health. We have found an antibody signature that can distinguish acute LD patients who continued to have chronic symptoms after treatment from those who returned to health. With that, we have designed a clinical study, MAESTRO, to test the accuracy of our ratiometric antibody score and to create an extensive biobank to investigate differences between acute and chronic LD, compared to Long COVID and healthy controls. Through the MIT Center for Clinical and Translational Research, we will collect blood, saliva, and urine samples, as well as optional sweat, throat swabs, and vaginal/menstrual samples. Biological specimen sampling will be paired with cognitive, eye, and hypermobility testing. We will also follow the acute LD participants who experience symptoms post-treatment, as well as matched participants from the other cohorts, longitudinally with follow-up visits at 6 and 12 months. These data will allow us to test our antibody ratio as a biomarker for predicting recovery from LD.