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.