Understanding Long Term Neurological Complications of COVID-19
Medically Reviewed by Kobi Nathan, Pharm.D., M.Ed., CDP, BCGP, AGSF
Written By Zuzanna Pociecha
Sleep Disorders
May 1, 2022
Zuzanna Pociecha is a student pharmacist at the Wegmans School of Pharmacy at St. John Fisher College and will graduate with her Pharm.D degree in May 2023. She plans to pursue postgraduate residency training to specialize as a clinical pharmacist in a hospital setting.
SARS-CoV-2 infection, known as COVID-19 disease, was first identified in Wuhan, China, in December of 2019. In just a short span of three months, it had spread across the globe and was officially declared a pandemic by the World Health Organization (WHO) in March of 2020.

It was a time of shock and uncertainty for everyone in the world. The world became still as most businesses, schools, and workplaces had closed down, and the only time we could see our friends and family was on a computer screen or six feet away behind a mask.

The SAR-CoV-2 virus is a type of coronavirus that causes COVID-19 disease. The family of coronaviruses has existed for a long time and was first discovered by a scientist in 1937.

The coronavirus that causes COVID-19 disease is a subtype of coronavirus that was more recently discovered and will cause infection on a scale of mild to severe in most people.

Two years after the pandemic started, so much has been discovered about the virus and disease. Vaccines and medications are now readily available to the entire population.

Normalcy has been mostly reinstated as schools, workplaces, and businesses have opened their doors after uncertainty.

A lot has changed since the initial “lockdown” of the start of the pandemic; however, so much more has still yet to be identified.

There is evidence of long-term brain injury and negative impact on cognitive function in historical pandemics and disease outbreaks such as the flu.

The flu pandemic of 1889 and 1892, known as the “Russian flu,” has been linked to long-term neurological effects such as severe nerve pain, chronic fatigue syndrome, headache, irritability, inflammation of the nerves, psychosis, anxiety, and paranoia.

Meanwhile, the flu pandemic of 1918-1919 has been linked to Encephalitis, Parkinsonism, and Catatonia, primarily affecting a person’s mobility.

Similarly, one of the biggest concerns of COVID-19 disease after the initial infection is its effect in the long term, especially with the population at highest risk; the elderly. It is essential to be aware of what could result from coronavirus disease five years from now, ten years, 15 years, etc.

The collected evidence so far suggests that the effects of covid-19 manifest as persistent symptoms in many patients.

These individuals are commonly known as the “long haulers.” COVID-19’s long-term effects (long covid) are being closely observed and studied by several investigators.

One systematic review confirms symptoms of impaired mental health, stomach, heart problems, inflammatory syndrome pain, and central nervous system effects.

Risk Factors For Severe COVID-19 infection

Severe COVID-19 illness is associated with further complications, often presenting as intense shortness of breath and needing a ventilator.

Severe disease could progress to critical conditions in which people develop Acute Respiratory Distress Syndrome, cardiac (heart) dysfunction, failure of multiple organ systems, and death.

People of advanced age (>65 years) are at high risk of developing severe COVID-19 infection.

According to the CDC, 81% of COVID-19-related deaths are accounted for by people of advanced age.

Other health problems or risk factors for severe disease include cancer, chronic kidney disease, organ transplant, chronic lung or liver disease, cystic fibrosis, diabetes, dementia, neurologic complications, heart disease, HIV infection, disabilities, mental health disorders, obesity, pregnancy, stroke, smoking, and other conditions.

Neurological Problems from COVID-19

It is unknown whether COVID-19 may cause diseases like Alzheimer’s Disease, Parkinson’s Disease, or Multiple Sclerosis, nor is it known if it accelerates illness in a person with the predisposing factors of the disease.

However, there is research being done in this field because there is reason to believe that COVID-19 affects the processes in the brain that are disrupted in diseases like Alzheimer’s Disease, Parkinson’s Disease, and Multiples Sclerosis.

COVID-19 and Alzheimer’s Disease

Alzheimer’s Disease, a neurological disease, is frequently recognized as memory loss and confusion that gets worse over time.

It has been shown that COVID-19 also plays a role in memory loss and confusion for a prolonged period. These symptoms were discovered in the new medical term coined “Long COVID.”

Essentially, Alzheimer’s Disease progresses when parts of the brain called neurons lose function and are lost.

This process is sped up by inflammation or swelling in the brain. COVID-19 itself will also speed up these processes.

In addition, the COVID-19 virus binds to a particular target called the ACE-2 receptor. The ACE-2 receptor is also expressed in the processes in the brain that promote the progression of Alzheimer’s Disease.

Studies are currently being done to determine whether there is a causal relationship between COVID-19 and Alzheimer’s Disease.

However, it is essential to consider that the complete progression of Alzheimer’s Disease often takes up to 20 years.

COVID-19 and Parkinson’s Disease

Parkinson’s Disease results from inflammation or swelling in the brain leading to loss of neurons and their function, similar to how Alzheimer’s Disease progresses.

The difference between Parkinson’s Disease and Alzheimer’s Disease is that Parkinson’s Disease primarily affects a part of the brain called the Substantia nigra striatum.

In contrast, Alzheimer’s Disease affects many parts of the brain. Since Parkinson’s Disease affects the Substantia nigra striatum, some of the common symptoms of Parkinson’s Disease involve tremors, limb rigidity, and movement disorders affecting one’s ability to walk.

We already know that COVID-19 causes cognitive decline (memory loss and confusion), so there is also reason to believe that COVID-19 can accelerate Parkinson’s Disease progression and onset and potentially affect the area of the brain that Parkinson’s Disease affects.

This is also a significant area of research for scientists and medical professionals and is currently being actively investigated. Another connection between Parkinson’s Disease and COVID-19 is the loss of taste and smell.

It is widely recognized that one of the first symptoms of Parkinson’s Disease is the loss of taste and smell.

COVID-19 and Multiple Sclerosis

Multiple Sclerosis (MS) is an autoimmune disorder that affects the brain and the spinal cord leading to numbness and tingling in the extremities, memory loss, pain, mood changes, and sometimes paralysis.

MS results from one’s immune system attacking the brain and spinal cord neurons by damaging the myelin, protecting the nerve fibers in a healthy brain.

When myelin is damaged, the connections of nerve fibers in the brain can no longer function resulting in the neurological symptoms of MS.

COVID-19 also causes demyelination in the brain and spinal cord due to a ‘cytokine storm,’ an intense inflammatory response during severe COVID-19 infection.

COVID-19 and Ischemic Stroke

There is direct evidence that individuals over the age of 50 are at high risk of suffering from ischemic stroke due to acute COVID-19 infection regardless of predisposing risk factors.

COVID-19 and other CNS complications There is additional evidence that covid-19 patients over 50 are at a higher risk for developing encephalopathy, Guillain-Barré syndrome, and critical illness neurological manifestations.

Less Prevalent Complications in the Elderly

Many medical conditions are less prevalent in the elderly that still occur in the younger population.

These conditions include demyelinating disease, loss of smell, and taste, encephalitis, myelitis, meningitis, and Acute Disseminated Encephalomyelitis (ADEM).

Demyelinating disease occurs at similar rates across all ages. It is a general condition in which the myelin sheath is deteriorated and is most commonly seen in disease states like Multiple Sclerosis.

This makes sense because the diagnosis of Multiple Sclerosis can occur at any point.

Being of greater age does not put you in a higher risk category for acquiring the disease but that does not mean you are less likely to be diagnosed with MS. 

Encephalitis, Myelitis, and Meningitis 

Encephalitis is generally acquired acutely post-infection of COVID-19 and can result in brain tissue inflammation.

Meanwhile, myelitis is the inflammation of the spinal cord, and meningitis is the inflammation of the brain and spinal cord that typically results from bacterial or viral infections. The development of encephalitis, myelitis, or meningitis due to COVID-19 infection was seen predominantly in children under the age of 19. 

 

Multisystem Inflammatory Syndrome in Children (MIS-C) 

Multisystem Inflammatory Syndrome in Children is a condition in which children present with chronic inflammation of several body organs such as the heart, brain, kidneys, lungs, skin, or eyes.22 This medical condition is mainly discovered in children after previous COVID-19 illness.

PICS – What is it and What the Elderly Need to Know

Post Intensive Care Syndrome (PICS) involves cognitive, mental, and physical symptoms that appear shortly after a patient has recovered and been discharged from an Intensive Care Unit.

The ICU experience for a patient may often be traumatizing. They are at a very high risk of developing delirium.

Patients are often put under sedation, and they may not remember anything from their hospital stay, known as “brain fog.”

Once a patient survives, they experience anxiety, depression, long-term cognitive decline, difficulty concentrating, chronic pain, and no improvement in general health.

In addition to PICS affecting patients who survive the ICU, PICS-F is a term to describe the hardships families face when helping their loved one who is primarily affected by PICS.

Family members and friends may suffer from grief, anxiety, depression, and stress associated with taking care of their loved ones and witnessing the suffering and pain they are in both their acute and chronic illnesses.

Generally speaking, more than 25-75% of ICU survivors experience PICS, and more than 80% of ICU survivors are readmitted to a rehabilitation or nursing facility within two years of being discharged from the ICU.

These statistics are expected to increase tremendously over the next few years due to the COVID-19 pandemic.

Conclusion

Patients with COVID-19 infection in critical condition and require an intensive care setting are at high risk of facing death or acquiring PICS if they recover from illness.

Once patients progress to this stage of disease, they often require mechanical ventilation.

Regardless of age, around 50% of patients that require mechanical ventilation in the ICU will acquire PICS.

Other risk factors for PICS development include stroke, alcoholism, acute respiratory distress syndrome (ARDS), cardiac arrest, glucose dysregulation, severe sepsis, trauma, renal replacement therapy, and prior cognitive impairment.

Many of these risk factors are seen in patients with COVID-19 infection. COVID-19 has caused over 6.2 million deaths and over 450,000,000 recovered cases as of April 2022.

Many people who have recovered from COVID-19 in an intensive care setting will face endless challenges for the rest of their lives.

Unfortunately, individuals who suffer from PICS will not be the same as before their critical illnesses.

People get better progressively, but it takes a multitude of time and effort from themselves and their loved ones.

We continue to witness the acute phase of the current COVID-19 pandemic, but it is anticipated that the long-term complications of COVID-19 and PICS will become the next public health crisis.

Health care professionals are still researching and learning more about this syndrome and how to help patients affected by this syndrome.

 In the meantime, awareness continues to be spread, and clinics are being set up to see patients and families suffering from the consequences of PICS.

Summary/Conclusion 

  • The elderly population is at a high risk of acquiring severe COVID-19 infection and has a higher occurrence of neurological complications associated with COVID-19 compared to the younger population
  • There are a lot of known, immediate neurological complications of COVID-19 infections such as ischemic stroke, headache, seizures, Guillain-Barre syndrome, loss of taste or smell, encephalopathies, inflammatory disease, and demyelinating disease 
  • There are a lot of unknown neurological complications of COVID-19 infection, but they are currently being researched and investigated.
  • COVID-19 ICU survivors are at high risk for Post Intensive Care Syndrome (PICS)
  • Thoughts for future concern include Alzheimer’s disease, Parkinson’s Disease, Multiple Sclerosis, expedited cognitive decline, Post Intensive Care Syndrome, and many other neurological implications
  • The best way to prevent severe COVID-19 infection is to get vaccinated on a scheduled basis according to the CDC guidelines and take precautions such as social distancing, washing your hands, and disinfecting high-touch surfaces

 

 

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