Headache as a Significant Central Nervous System Manifestation of COVID-19 Infection

In recent years, the world has witnessed the emergence of dangerous respiratory diseases with coronaviruses, including the severe acute respiratory syndrome (SARS) by the SARS-CoV, Middle East respiratory syndrome (MERS) by the MERS-CoV, and coronavirus disease 2019 (COVID-19) by the SARS-CoV-2. The disease now affects most countries in the world. Coronavirus is generally known to cause respiratory disease, but clinical and experimental studies show that this disorder affects several organs including the central nervous system (CNS).1-3 The CNS effects of COVID-19 are not well-known owing to being an emerging phenomenon, however, it is worth understanding. The virus enters the cells of the human body using the cellular receptor angiotensinconverting enzyme 2 (ACE2). In a normal condition, this receptor is expressed in very small amounts in the CNS. The virus can be transmitted to the CNS through systemic circulation or across the cribriform plate of the ethmoid bone in the early and secondary stages of COVID-19 infection. Broad spectrum of neurological manifestations such as ageusia, anosmia, headache, sensory disturbances and epilepsy have been observed in some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease due to hyper coagulation state is also emerging as an important complication. Altered level of consciousness and encephalitis are other presentations in patients with COVID-19.4,5 Almost all the articles reviewed focused on macro-and microscopic changes in the lungs, and only a handful of information from other organs and systemic findings were presented. Comprehensive study after autopsy in the brain is very important and more research needs to be done.6-9 A better understanding of the function of coronavirus in the CNS and accurate identification of the damage can help in treatment planning and prognosis of the disease.10,11 In addition, hypoxia may occur in the CNS (hypoxic ischemic encephalopathy) due to respiratory failure. Thrombotic microangiopathy can also occur.12 Hence, it is of paramount importance that in the early and uncomplicated stages of coronavirus infection, the patient’s CNS be examined. There is still insufficient information to provide a complete picture of the pathophysiology of SARS-CoV-2 infection. Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish nonspecific complications of severe disease (e.g. hypoxic encephalopathy and critical care neuropathy).4 In light of the above mentioned, further studies on patients with progressive or worsening CNS findings should be performed more carefully to make the undiscovered effects of this virus on the CNS clearer to the world. So far, we have mentioned CNS involvement in general and now we aim to give a brief summary of studies on headache attributed to COVID-19 infection. The reports on the neurological presentations are rising significantly and headache has the lead on the symptom list. Headache associated with systemic infections is usually nonspecific and actually there are no particular distinguishing or characteristic features. It was reported that headache was a frequent symptom in COVID-19 infection and there was an extreme diversity in its characteristics. In one observational case study that included patients Headache as a Significant Central Nervous System Manifestation of COVID-19 Infection Saeideh Salehizadeh1 ID , Negar Bizhani2 ID , Zahra Arab-Mazar2 ID , Sara Rahmati Roodsari3* ID