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About: Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its ‘semeiotic’. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.

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