COVID-19 is the name of sickness headed by SARS-CoV-2, which gated the confinement restrictions since March 2020. At the beginning the S protein was identified as the "key" that enhances entering human body, due to its affinity with ACE2 receptor. ACE2 receptor is known to be expressed in a variety of tissues in a manner in which that location increases their infection-probabilities in exposure to this virus. The brain contains two regions where ACE2 is manly expressed: 1) The olfactory bulb which is thought to be involved in loss of smell and facilitating entering to the Central Nervous System, on the other hand 2) the brainstem keeps imbibed the Pre-Botzinger complex, a mediator of respiratory rhythm, showed its implications in oxygen depletion because of abnormal working of O2, and CO2 sensing chemoreceptors. In concern with PNS it is considered virus-nociceptors interaction as the most likely reason to muscular pain and headache.