Background: The symptom burden experienced by patients with cancer who contract the COVID-19 (C19) infection remains to be fully understood. To accurately assess this symptom burden, we developed a valid, reliable patient-reported outcome (PRO) measure of C19 symptoms combined with a known measure of cancer symptom burden. Methods: Within the institutional initiative on COVID-19 and cancer named Data-Driven Determinants for COVID-19 Oncology Discovery Effort (D3CODE), patients with cancer and PCR-positive C19 tests were invited to participate in this longitudinal study after providing consent. Pts completed the EQ-5D-5L and the 13 symptom severity and 6 interference items of the core MD Anderson Symptom Inventory (MDASI) plus 14 COVID-specific symptom items generated from literature and expert review. Items were measured on a 0-10 scale, 0 = none to 10 = worst imaginable symptom or interference. Demographic and disease information was collected. Psychometric procedures determined validity and reliability of the MDASI-COVID. Results: 600 pts enrolled, mean age 56.5y (range 20 to 91y). 59% female, 80% white. 78% solid tumors, 19% heme cancers. 12.5% required hospitalization for C19. Median number of days between positive C19 test and PRO completion was 17 days. Mean overall health rating on EQ-5D-5L was 78.3 (SD 19.6), best being 100. Highest mean (M) severity symptoms on the MDASI-COVID were fatigue (M 3.45, SD 2.17), drowsiness (M 2.50, SD 2.89), sleep disturbance (M 2.44, SD 2.99), malaise (M 2.37, SD 3.05), and distress (M 2.27, SD 2.90). Most severe (≥ 7) symptoms) reported were fatigue (21.3% of pts), change in taste (14.8%), change in smell (14.4%), malaise (14.3%), sleep disturbance (14.3%), and drowsiness (14%). Internal consistency (Cronbach α) of the 27 symptom items was 0.957, of the 6 interference items was 0.937. Mean severity of the 27 symptom items was significantly correlated with overall EQ-5D-5L health rating (correlation = -0.45, P < 0.0005), demonstrating concurrent validity. Mean symptom severity and interference showed known-group validity between patients who required C19 hospitalization (symptom M 2.32, SD 2.09; interference M 3.29, SD 3.02) and those who did not (symptom M 1.69, SD 1.85; interference M 2.20, SD 2.64) (symptom P 0.007; interference P 0.004). Conclusions: We have validated a novel PRO, the MDASI-COVID, to quantify the combined symptom burden in patients with cancer and COVID-19. This measure allows longitudinal evaluation of COVID-19 on cancer symptom burden and provide clinicians with an accurate tool for ongoing symptom assessment and management. Longitudinal analysis on long-term symptoms related to COVID-19 and cancer are ongoing.