COVID-19 is a Real Headache!

Abstract

After the emergence of a novel coronavirus named SARS-CoV-2, coronavirus disease 2019 (COVID-19) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID-19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%-34% of the hospitalized COVID-19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID-19 patients were new-onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19. Symptomatic COVID-19 patients, around 6%-10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS-CoV-2 directly or through the vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia. We concluded that as a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.

Keywords: angiotensin-converting enzyme 2; coronavirus disease 2019; headache pathophysiology; headache symptoms; inflammatory mediators; vasculopathy.

Fig. 1

Schematic diagram of pathophysiological role of Angiotensin‐converting enzyme 2 (ACE2) in COVID‐19. Angiotensin II (Ang II), produced by ACE, acts through AT1 receptor (AT1R) and mediates various functions all around the body including peripheral and central nervous system (red arrows). On the contrary, Ang 1‐7 generated by cleavage of Ang II by ACE2, acts through Mas receptor (MasR) and exert opposite functions (green arrows). Thereby, ACE2 not only terminates Ang II, but also generates a peptide, counterbalancing the effects of Ang II/AT1R axis. Upon SARS‐CoV‐2 binding, internalization of ACE2 downregulates its protective functions, leaving pathogenic Ang II/AT1R actions unbalanced. Endothelial Nitric Oxide Synthase (eNOS), Reactive Oxygen Species (ROS).