Abstract
Fever of Unknown Origin (FUO) remains a diagnostic challenge for clinicians, with multiple infectious and non-infectious etiologies. SARS-CoV-2 can determine a prolonged viral shedding in the immunocompromised host, firstly in those receiving B-cell targeted therapies, being responsible of persistent infection which may configure as a FUO. We report two cases of long-lasting fever in patients with multiple sclerosis and B-cell depletion, finally diagnosed as COVID-19. We suggest the inclusion of SARS-CoV-2 testing in the differential diagnosis of FUO.