Several potential pathophysiological mechanisms were suggested for headaches: A direct invasion of SARS-CoV-2 to the trigeminal nerve endings in the nasal cavity, trigemino-vascular activation due to involvement of the endothelial cells of the vessel walls with a high expression of angiotensin-converting enzyme (ACE2), and the release of the proinflammatory mediators and cytokines during COVID-19 might stimulate the perivascular trigeminal nerve endings [1,26]. The gene discussed is ACE; the disease is Headache.