As the meninges have high quantities of blood vessels and ACE2, damage to these blood vessels and meninges inflammation resulting from SARS-Cov2 can lead to symptoms of meningitis, such as acute headache, stiff neck, confusion, and seizure. 

Syracuse University

- Encephalopathy (overall)
- Ischemic Stroke
- Multisystem Inflammatory Syndrome in Children (MIS-C)
- Induce brain and spine demyelinating lesions
- Mast cell activation
- Acute cerebrovascular disease 
- Intracranial hemorrhage
- Seizure (caused by meningitis)
- Neuroinflammatory syndromes 
- Post-infection cerebral changes

COVID-19 Reports on Patient Neurological Symptoms, Organized by Symptoms Affecting the CNS

Fotuhi, M., Mian, A., Meysami, S., & Raji, C. A. (2020). Neurobiology of COVID-19. Journal of Alzheimers Disease, 76(1), 3-19. doi:10.3233/jad-200581
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200581

Neurobiology of COVID-19

In studies conducted in Wuhan, China and France, 93 patients total were found with encephalopathy. Most of these patients experienced symptoms such as dizziness, headaches, and a reduced state of consciousness.

Encephalopathy in COVID-19 Patients.

- Encephalopathy
- Meningism
- Headaches
- Ataxia
- Dysarthria
- Dysphagia
- Splenium of the corpus callosum (SCC) lesions

Multisystem Inflammatory Syndrome in Children (MIS-C) in COVID-19 Patients: CNS Symptoms

SARS-CoV-2 is known to activate mast cells in affected patients, along with other immune cells including monocytes/macrophages, neutrophils, T cells, killer cells, and resident tissue epithelial and endothelial cells. These various groups cells have been thought to induce the "cytokine storm syndrome" that is experienced by COVID-19 patients. However, since mast cells are well-expressed throughout the body (including the CNS) and are involved in certain neuroinflammatory diseases, it is hypothesized that their activation by SARS-CoV-2 upregulates certain neuroinflammatory responses, which may result in some of the other symptoms observed in COVID-19 patients, including ischemic stroke.

Mast Cell Activation in COVID-19 Patients

In the study by Li et al., a majority of the 221 COVID-19 patients had ischemic infarcts in both small and large arterial vessels, and 13 (5.4%) had imaging-confirmed cerebrovascular disease. Another study by Oxley et al. reported 5 patients under age 50 with cerebrovascular disease and noted that even without presenting typical respiratory symptoms, young healthy patients with COVID-19 may experience large strokes. The 5 young patients were treated with either antiplatelet or anticoagulation.


Acute Cerebrovascular Disease in COVID-19 Patients

While a majority of COVID-19-related strokes have been ischemic, a few have been intercranial hemorrhage, although the causes of the latter are not yet understood. One potential explanation is that SARS-Cov2 binds to and downregulates ACE2, slowing the conversion of angiotensin II to angiotensin, and that since higher levels of angiotensin II are associated with vasoconstriction, this causes blood vessels in the brain to rupture. ACE2 polymorphism may explain the increased risk of intracranial hemorrhage among the East Asian population.


Intracranial Hemorrhage in COVID-19 Patients

Potential Link Between Seizure and Meningitis in COVID-19 Patients

Neuroinflammation is an innate immune response to percieved threats in the nervous system, which can lead to neurological complications. In a study of 43 patients, 12 developed neuroinflammatory syndromes, including:

- Encephalitis 
- Acute disseminated encephalomyelitis (including acute haemorrhagic leucoencephalitis and ADEM-like illnesses)
- Myelitis

Neuroinflammatory Syndromes in COVID-19 Patients 

Several studies have suggested that COVID-19 patients have long-term structural changes within certain structures in their brains. As an example, an MRI- and DTI-based 3-month follow up study from Lu et al. (2020) found that patients have significantly higher gray matter volumes in their olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus, and right cingulate gyrus. General diffusivity had declined. Left hemisphere changes correlated with memory loses, while other right hemisphere changes correlated with smell loss. 

Post-Infection Cerebral Changes in COVID-19 Patients

- Impact of COVID-19 on Outcomes in Ischemic Stroke Patients in the United States
- COVID-19 Is an Independent Risk Factor for Acute Ischemic Stroke
- Prevalence and Outcomes of Acute Ischemic Stroke Among Patients ≤50 Years of Age With Laboratory Confirmed COVID-19 Infection
- Characteristics and Comparison of 32 COVID-19 and Non-COVID-19 Ischemic Strokes and Historical Stroke Patients
- Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke

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