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INVITED EDITORIAL
Year : 2020  |  Volume : 8  |  Issue : 1  |  Page : 2-4

Cerebrovascular complications of COVID-19


BRAINS Neuro Spine Center, Bengaluru, Karnataka, India

Date of Submission19-Aug-2020
Date of Acceptance22-Aug-2020
Date of Web Publication1-Oct-2020

Correspondence Address:
Dr. N K Venkataramana
BRAINS Neuro Spine Center, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcvs.jcvs_13_20

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How to cite this article:
Venkataramana N K. Cerebrovascular complications of COVID-19. J Cerebrovasc Sci 2020;8:2-4

How to cite this URL:
Venkataramana N K. Cerebrovascular complications of COVID-19. J Cerebrovasc Sci [serial online] 2020 [cited 2020 Nov 27];8:2-4. Available from: http://www.jcvs.com/text.asp?2020/8/1/2/296920



The world is going through the crisis of corona infection as the COVID-19 pandemic. Although the affected have a wide spectrum ranging from a symptomatic to fatal, many factors about the virus still remains a puzzle. Although significant numbers have recovered, long-term implications are yet to be seen and understood. Viruses are small particles whose origin remains controversial. Virus is a Latin word meaning 'Slimy liquid or Poison'. They can attack humans, animals as well as plants; hence, Beijerinck in 1898 described them as Contagium vivum fluidum. They are less than 200 nm in size and hence invisible. Modern techniques such as culturing cells on glass and later the electron microscope could reveal the true nature of them.

Unlike bacteria, viruses cannot live independently. They need a host to live. In biology, life is characterised with certain known facts such as growth, reproduction, maintaining homoeostasis, response to stimuli, to carry out metabolic processes and evolve as population. By these attributes, viruses cannot be classified as living organisms. They remain as obligatory intracellular parasites. Yet, they can maintain themselves and evolve over time that makes them very special. Hence, they confuse the biologists till today and probably represent different types of organisms altogether in the tree of life. Although, in strict sense, they are not living organisms, they occupy a very special taxonomic position, placed in their own kingdom. Probably, they represent a parallel evolution.

A true virus contains deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) and protein. The nucleic acid encodes the genetic information that is unique for each type of virus. The extracellular part called virion contains a unique protein that helps identify the host; virus has a shell called capsid that surrounds the nucleic acid. Each virus has only either DNA or RNA and never both. They can be further characterised by nature and type of nucleic acid such as single strand or double strand. Viruses do not have ribosomes hence cannot synthesise proteins on their own. Similarly, they do not have adenosine triphosphate and energy storage system. Hence, compulsorily, they have to depend on a host cell for energy and protein synthesis. They are compelled to be parasites. They can reproduce only in a host cell.

Normally, virus reaches a cell and gets attached to it by the help of virion called adsorption. Then, it penetrates the cell. Subsequent action depends upon its nature and congenial environment. In suitable situations, they can multiply and destroy the host cells or can remain dormant. Once environment is suitable, the nucleic acid of virus gets injected into the cytoplasm of the host cell. Then, this nucleic acid gets integrated with the nucleic acid of the host cell. The moment this happens, the host cell becomes a slave and behaves like a viral nucleic acid completely. From then on, all the instructions to the host cell goes from the viral nucleic acid. Depending on certain chemical and physical factors, the viral nucleic acid instructs the host ribosomes to produce viral proteins. It will also use the energy reserves of host cells and start multiplying. The host cell actually produces the exact photo prints of viruses. They assemble and produce fresh virions. Then, they cause the lysis of host cell killing them instantly. The release of pro gene virions moves across into another adjacent cell to repeat the process. Hence, viruses have two unique abilities such as entering a cell as particles and taking total control once they are in.

The origin of viruses is controversial. Several hypothetical propositions are there.

Virus first theory proposes that viruses existed in the pre-cellular world. They were self-replicating units. With time, they got more organised and acquired enzymes of synthesis. These enzymes synthesised membranes around forming a cell and cellular organisms. Accordingly, they existed before bacteria. If so, why they remain as particles till today is difficult to explain. Evolution and this cannot go together.

Others proposed the progressive or escape theory – viruses formed from the genetic elements that gained ability to move between cells. This phenomenon is clearly seen in certain viruses. Later on, scientists also put forward the regressive theory. Through a steady regressive or reductive process, they have lost the genetic information from free living ancestors and became parasites. However, none of them are satisfactory as on today. There is evidence that viruses existed simultaneously and were using bacteria to multiply. Scientists also think that a fragment of DNA or RNA from prokaryotic or eukaryotic host became viruses. There were no fossils identified for viruses. Hence, as on today, the origin of viruses remains conjunctural. Virologists believe that both viruses and bacteria were together at the same time, and viral evolution also happened at the same rate. Hence, the viral evolution is described as 'polyphylatic' evolution. They are probably evolutionary off shoots.

COVID-19 infection from corona, the RNA virus, is known to cause acute respiratory distress syndrome and hyper-immune response called cytokine storm as the cause of morbidity and mortality. However, a hyper-coagulable state has been described in the critical patients, leading to cerebrovascular complications. Still, clinicians are understanding the immediate, acute as well as long-term complications associated with COVID-19 infection. Recent accumulated evidence shows that COVID-19 infection is an independent risk factor for the stroke. New-onset cerebrovascular disease is noted in 5.9% of patients afflicted by COVID. Among the neurological complications, stroke is the leading problem by 85%. The remaining includes cerebral venous thrombosis, intra-cerebral haemorrhage, subarachnoid haemorrhage apart from encephalopathy and seizures. Large vessels are affected in majority contributing to 46% of the cerebrovascular disease. The average time of onset of stroke is 12 days from the start of the infection. Young individuals, particularly belonging to Black Hispanic and Asian community, are more prone. In the population with stroke, COVID as a cause or concomitant infection is a worldwide debate. However, the pooled analysis of the published data so far indicates that the stroke risk increases by 2.5-fold as per the odds of severe COVID infection. The occurrence of stroke in COVID infection increases the risk of death, need for intensive care, as well as ventilatory care, and is also known to increase the mortality rate. Presence of pneumonia in critical COVID patients is an added risk factor for the occurrence of stroke.

Presence of hyper-coagulable state in these patients can explain the increased risk for the cerebrovascular system integrity. In addition, they also have increased inflammatory markers. The haemorrhagic transformation of existing stroke is also known in COVID infection. Presence of arterial clots has been described in 3.7% of patients, from the Netherlands in their foremost publications. Subsequently, large-vessel occlusion as a cause of stroke was described from the UK. Increased mortality in the elderly came from the experience of New York. China has described bilateral strokes in the brain. Computed tomography (CT) scans showed classical evidence of stroke in the brain with or without haemorrhagic transformation. Viral neurotropism, endothelial dysfunction, coagulopathy, inflammation, hypoxia and embolic phenomena from the heart are some of the possible mechanisms described for the occurrence COVID-related strokes.

Neurotropism is demonstrated by the presence of virus in the cerebrospinal fluid, neuronal cells as well as endothelial cells. The coronavirus binds to the receptors through the angiotensin-conversion enzyme 2 (ACE2) present in the spike protein.

ACE2 is expressed abundantly in the cerebral endothelial cells. Binding of viruses to these receptors disrupts the auto-regulatory function, leading to elevated blood pressure and rupture of vessels as well as endothelial dysfunction. Alteration of coagulation pathway is another proposed mechanism. Elevation of the D-dimer, fibrin and fibrinogen degradation products suggests the possibility of such mechanism. At the same time, prothrombin time (PT) and anti-thrombin activity is decreased. The monocytes and endothelial activation lead to the release of cytokines causing disseminated intravascular coagulation. Few others implied cytokine-related systemic inflammation mediated by interleukin 6. This inflammatory response can eventually lead to stroke. As this virus can cause myocardial injury, associated emboli formation could lead to embolic stroke as demonstrated by the presence of clots in the larger vessels. Significant involvement of the lungs can cause prolonged hypoxia which in turn can contribute to the origin of stroke.

Majority of times, stroke occurs in already hospitalised patients. It is easier to miss the findings in them due to blunting of sensorium as well as limited clinical examination. CT scan is diagnostic. There could be haemorrhagic transformation apart from proper intra-cerebral haemorrhage.

No standard treatment is in vogue till now as the evidence is still growing. Anticoagulant as an empirical treatment is questionable with elevated D-dimer. Although anti-platelets are being used routinely, the data are insufficient to support its therapeutic as well as prophylactic roles. We still need to watch these affected patients or long term for all possible complications that can occur in immediate post-COVID or in the long term. Meticulous data collection and reviews will help us establish the possible clinical correlations in due course of time. Till then, it is important to identify the high-risk group and be vigilant in identifying such complications to treat them effectively in time.






 

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