Impact of COVID 19 on the Nervous System

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Original Editor - User Name
Top Contributors - Srishti Banerjee, Kim Jackson, Aminat Abolade and Rishika Babburu

Introduction

With the outbreak of coronavirus, the major areas of concern were the respiratory system. However, it has been established that coronavirus affection can extend beyond the respiratory system and one of the deadly areas of affection is the effect of the virus on the nervous system. A wide range of neurological manifestations have been reported during and post covid conditions.

Pathophysiology

Invasion via the olfactory route.

Loss of smell has been reported as one of the earliest symptoms of covid infection. It has been established by the evidence of an increase in MRI signal to the olfactory cortex suggestive of infection in the nervous system. The virus gains access to the central nervous system via the bloodstream, infecting the endothelial cells. Secondly the virus can enter the peripheral nervous system through retrograde neuronal routes. The virus could be internalized in nerve terminals by endocytosis, transported retrogradely, and spread trans-synaptically to other brain regions

Angiotensin-converting enzyme -2 ( ACE-2) receptor present in the nasal mucosa is exploited by the virus. ACE-2 receptor is also present in organs such as kidneys , lungs, and in tissues of the nervous system. The presence of ACE-2 receptors in the tissues of the nervous system is hypothesized to be the reason that the virus leads to neurological manifestations.

The virus from the general circulation can pass into the cerebral circulation, where due to sluggish movement of the blood in the microcirculation along with the high rate of the load from the initial sites of infection facilitates the interaction of a protein present in the coronavirus known as spike protein ( S protein ) with the ACE-2 receptors present in the capillary endothelium. Following this, there is the budding of the virus in the capillary endothelium leading to the spread of the virus in areas of the brain and brainstem via Virchow-Robin spaces surrounding arterioles and venules.

Cytokine Storm is another mechanism reported to be responsible for neurological manifestations in covid infection. Cytokine storm is defined as dysfunctional, uncontrolled, continuous activation of inflammation. This leads to acute respiratory distress syndrome, renal failure, myocardial injury, the severity of illness, the requirement of intensive care unit admission, the requirement of mechanical ventilation, and mortality. The presence of inflammatory markers such as C-reactive protein and leukocytes confirm the presence of cytokine storm. Diffuse illness of CNS has been reported and temporal association between inflammatory markers and CNS dysfunction is yet to be established. However, it is known that release of of interleukin-6 causes vascular leakage and activation of complement and coagulation cascades , in addition to this patients with severe covid infection presents with higher levels of D-dimer, which is a marker of a hypercoagulable state and endogenous fibrinolysis . These may be the factors that cause acute cerebrovascular disease. Cytokine storm is also responsible for causing arthralgia.

Pneumonia is a common clinical feature of covid infection , however the systemic hypoxia occuring due to pneumonia causes damage to the brain cells and other nerve cells.