Byline: Farrokh Alemi, Departments of Health Administration and Policy (Dr Alemi and Ms Guralnik) and Global and Community Health (Dr Roess), George Mason University, Fairfax, Virginia; and Health Administration and Policy, George Mason University College of Health, Fairfax, Virginia (Dr Vang).; Jee Vang; Elina Guralnik; Amira Roess Abstract BACKGROUND: The importance of various patient-reported signs and symptoms to the diagnosis of coronavirus disease 2019 (COVID-19) changes during, and outside, of the flu season. None of the current published studies, which focus on diagnosis of COVID-19, have taken this seasonality into account. OBJECTIVE: To develop predictive algorithm, which estimates the probability of having COVID-19 based on symptoms, and which incorporates the seasonality and prevalence of influenza and influenza-like illness data. METHODS: Differential diagnosis of COVID-19 and influenza relies on demographic characteristics (age, race, and gender), and respiratory (eg, fever, cough, and runny nose), gastrointestinal (eg, diarrhea, nausea, and loss of appetite), and neurological (eg, anosmia and headache) signs and symptoms. The analysis was based on the symptoms reported by COVID-19 patients, 774 patients in China and 273 patients in the United States. The analysis also included 2885 influenza and 884 influenza-like illnesses in US patients. Accuracy of the predictions was calculated using the average area under the receiver operating characteristic (AROC) curves. RESULTS: The likelihood ratio for symptoms, such as cough, depended on the flu season--sometimes indicating COVID-19 and other times indicating the reverse. In 30-fold cross-validated data, the symptoms accurately predicted COVID-19 (AROC of 0.79), showing that symptoms can be used to screen patients in the community and prior to testing. CONCLUSION: Community-based health care providers should follow different signs and symptoms for diagnosing COVID-19 during, and outside of, influenza season.