Vascular manifestations of COVID-19 comprise either venous or arterial thrombosis or stroke in subjects under the age of 50, sometimes with a severe phenotype that can resemble the “catastrophic” clinical picture associated with antiphospholipid antibodies (aPL). In patients with systemic autoimmune diseases such as Systemic Lupus Erythematosus (SLE), aPL represent the major cause of thrombosis (either arterial or venous or microangiopathic) and pregnancy morbidity. aPL are pathogenic autoantibodies that can cause the same vascular and obstetric manifestations also in subjects without any other autoimmune disease, suffering from the so called Primary Antiphospholipid Syndrome (APS) [43]. The more severe form of APS (the “catastrophic” APS, CAPS) is characterized by a rapidly occurring multiorgan thrombotic damage with histopathological evidence of microangiopathy [44], recalling pictures described in patients with COVID-19. CAPS is usually preceded by a precipitating factor, which is an infection in the majority of the cases [45]. The link between infection and aPL was first observed when patients with different autoimmune conditions were found to be positive for the serological test of syphilis, whose antigen was described as a mixture of phospholipids, including cardiolipin [46]. Nowadays, the detection of aPL is performed by anticardiolipin (aCL) and anti-beta2glicoprotein I (anti-b2GPI) immunoassays and by the functional coagulation test lupus anticoagulant (LA), according to the international consensus APS classification criteria [47].