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COVID-19 is most commonly characterised by fever, cough, and breathing difficulties and is known to affect multiple organ systems in the body.  

Research suggests that almost half of the patients of coronavirus disease report neurological symptoms of COVID-19 including confusion, delirium, headache and dizziness. Another neurological symptom, sudden loss of sense of smell is suggested to be one of the stronger indicators of COVID-19 infection when it appears along with the standard flu-like symptoms of the condition.

Some of the neurological symptoms are temporary and resolve themselves gradually along with the infection. However, autopsy reports from early 2020 suggest that the virus can enter the cerebrospinal fluid and may even cause encephalitis (swelling in the brain) and brain damage. 

Since the early days of the pandemic, researchers have been warning about possible long-term neurological impacts of COVID-19 even after the acute disease is resolved.

Over the past few months, patients have reported lingering neurological symptoms ranging from brain fog to depression and a persistent loss of smell. 

However, experts suggest that longitudinal studies are still needed to understand the full scope of the long term effects of COVID-19 on the brain. (Read more: Permanent lung damage in COVID-19)

Here is what we know so far about the possible long term effects of COVID-19 on the brain:

  1. How does COVID-19 enter the brain?
  2. Effects of COVID-19 on the brain and central nervous system
  3. Long term effects of COVID-19 on brain
  4. Doctors for Can COVID-19 cause permanent brain damage?
  5. COVID-19 linked brain nerve damage seen in 11-year-old; AIIMS doctors to write up a case study

SARS-CoV-2 mostly transmits through respiratory droplets. When an infected person coughs, sneezes or talks, the droplets from their mouth can stay in the air for a while but then fall on nearby objects. When a healthy person touches these virus-contaminated objects, the virus sticks to their hands. It enters the person’s respiratory tract when the individual touches their nose or mouth without washing hands. 

There are various theories of how COVID-19 enters and affects the brain:

  • ACE2 receptors, the cell surface receptors that the COVID-19 causing virus uses to enter healthy cells, are present in the brain. The receptors have been found on neurons in the cerebral cortex, hypothalamus, substantia nigra (mid-brain basal ganglia structure) and the brain stem.
  • It is suggested that the virus enters the brain through the olfactory bulbs present in the nose. However, in some studies, SARS-CoV-2 was not found in the immediate areas in the olfactory lobe even when it was found in the patient’s brain.
  • Another suggestion was that the virus travels through synapses (the connections between neurons) of the trigeminal and vagus nerve from the respiratory tract and the gut. This would also suggest the spread of the virus and its effect on the peripheral nervous system.
  • And the final suggested mechanism is through the lymphatic or circulatory system, as the virus directly diffuses through the vascular endothelium (the lining of the blood vessels) in the brain. SARS-CoV-2 has been found scattered in the brain, clustering more around the blood vessels. 

Scientists are still not sure about which of these routes the virus actually takes to affect the peripheral and central nervous system.

What causes brain damage in COVID-19?

As with the mode of spread to the CNS (central nervous system), the exact cause of brain damage in COVID-19 has also not been determined yet: experts indicate that it could be due to the viral infection itself or the inflammation that occurs when the body responds to the infection

Read more: COVID-19 and inflammation

In an article published in Nature, Dr Michael Zandi, a neurologist associated with the University College London, suggested that it is highly unlikely that a virus can cause a CNS infection and that damage due to inflammation seems the more likely cause. However, nothing can be said for sure as of now.

In a study done by Dr Zandi and his colleagues, inflammatory disorders like encephalitis and encephalomyelitis (inflammation of the brain and spinal cord) were seen in COVID-19 patients both during and after the acute disease is over.

You might also be interested in Can COVID-19 cause permanent heart damage?

COVID-19 presents with an array of neurological symptoms that may originate from infection in various areas of the brain. Here is a list of these symptoms as per a study published in the journal Therapeutic Advances in Neurological Disorders:

Symptoms associated with localisation of infection in the CNS:

Symptoms associated with localisation in the peripheral nervous system (PNS)

Symptoms associated with localisation in muscles

However, as already mentioned, no data has yet proven that the neurological symptoms of COVID-19 are due to the infection itself. Increased risk of stroke in COVID-19 patients has been linked to inflammation and blood clotting. Stroke, in turn, is linked to hypoxemia (low oxygen in the blood) and brain damage. Similarly, symptoms like headache and muscle pain may also occur due to systemic inflammation, rather than negative effects on the brain.

As of October 2020, nearly 10 months since the first case of COVID-19 was reported in Wuhan, China, scientists are still investigating how SARS-CoV-2 works in an acute infection.

Additionally, as more people are recovering from the infection, meaning they get two negative RT-PCR results within a span of a day, the long term effects of the disease are being studied now.

Long COVID is the term used to denote the symptoms that coronavirus patients are reporting even after they get discharged from the hospital. While these symptoms mostly include persistent fatigue, chest pain and cough, patients have also reported neurological symptoms like confusion, brain fog and anosmia (loss of smell) that don't seem to be going away.

According to an article published in the journal Anesthesia & Analgesia, COVID-19 patients suffer from depression and anxiety due to prolonged separation from their loved ones and society and the many ICU procedures they undergo. The prolonged hospital stay also exacerbates their preexisting mental health conditions. Generalised inflammation and neurological tropism of the virus is also indicated to lead to post COVID muscle atrophy. (Neurological tropism is one way to say that the virus can preferentially attack the nervous system). 

Loss of myelin sheath (the outer covering of brain cells)—similar to what is seen in multiple sclerosis—was seen in a 54-year-old woman recovering from COVID-19. She had anosmia, headache and loss of taste during acute infection. Myelin sheath helps quickly transfer signals between brain cells. This demyelination was reported in a case study to cause seizures

A study published in the journal The Clinical Neuropsychologist suggested that those who experience symptoms like brain fog, headache, fatigue, sleep disturbance and anxiety after recovering from COVID-19 may be suffering from PTSD. As per the study, the neurological symptoms of COVID-19 suggest the effect of the disease on the brain. However, when it comes to the long term effects on the brain, it becomes really difficult to differentiate the ones caused by the infection and those that are more psychological.

Patients who recover from COVID-19, especially those who were intubated, admitted in the ICU or needed mechanical ventilation, may worry that their brain is permanently damaged by the disease. Those who suffered from delirium or psychosis may be plagued by fear or hallucinations long after they are cured of the disease. Studies have suggested that even those with otherwise mild COVID-19 develop neurological symptoms as one of the major presentations of the disease. (Read more: Post-COVID care for patients who are recovering)

But not every patient with persistent neurological symptoms actually has brain damage due to the infection. That said, due to the paucity of data, nothing can be confirmed about the prevalence of brain damage and the associated neurological symptoms in COVID-19 patients.

Dr. Arun R

Dr. Arun R

Infectious Disease
5 Years of Experience

Dr. Neha Gupta

Dr. Neha Gupta

Infectious Disease
16 Years of Experience

Dr. Lalit Shishara

Dr. Lalit Shishara

Infectious Disease
8 Years of Experience

Dr. Alok Mishra

Dr. Alok Mishra

Infectious Disease
5 Years of Experience

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References

  1. Yeshun Wu, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020 Jul; 87: 18–22. PMID: 32240762
  2. Pereira Antonio. Long-Term Neurological Threats of COVID-19: A Call to Update the Thinking About the Outcomes of the Coronavirus Pandemic. Front Neurol. 2020; 11: 308. PMID: 32362868.
  3. T Greenhalgh. Management of post-acute covid-19 in primary care. BMJ 2020;370:m3026.
  4. Paterson Ross W, et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain, awaa240. 2020 July.
  5. Tsivgoulis Georgios, et al. Neurological manifestations and implications of COVID-19 pandemic. Ther Adv Neurol Disord. 2020; 13: 1756286420932036. PMID: 32565914.
  6. Vittori Alessandro, et al. COVID-19 Pandemic Acute Respiratory Distress Syndrome Survivors: Pain After the Storm?. Anesthesia & Analgesia, July 2020; 131(1): 117-119.
  7. Zanin Luca, et al. SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir (Wien). 2020 May 4 : 1–4. PMID: 32367205.
  8. UCLA health [Internet]. University of California. Oakland. California. US; Brain fog' following COVID-19 recovery may indicate PTSD
  9. Yavarpour-Bali H. and Ghasemi-Kasman M. Update on neurological manifestations of COVID-19.. Life Sciences, 15 September 2020; 257:118063. Epub 9 July 2020. PMID: 32652139.
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