Long COVID: Neuropathies

Acute viral infection can be very challenging for both patients and their clinicians,  but the infection is also contributing to various complications throughout multiple systems and organs in the body. Viral infection can have long-term consequences for both the central nervous system (CNS) and the peripheral nervous system (PNS). SARS-CoV-2-associated PNS complications affect many people with Long COVID, causing a variety of different neuropathies and symptoms. But what is peripheral neuropathy, how is it related to COVID, and what can you expect if you experience post-COVID neuropathy?

What is Peripheral Neuropathy?

The peripheral nervous system (PNS) is a complex communication network of nerves that transport signals from the central nervous system (CNS) to areas throughout your body. The messages that travel through the PNS can include everything from telling muscles to contract, letting you know that your feet are cold, or helping to control your heart and blood vessels. Peripheral neuropathy is an umbrella term for over 100 different types of conditions that involve damage to the peripheral nerves. 

Nerve damage can cause nerve signaling disruption in three different ways: a complete loss of communication through the nerves, incorrect communication, or communication being sent when it shouldn’t. For example, if a person has a complete loss of nerve communication, they may experience numbness or a loss of feeling in the affected area. For those with incorrect communication, something that should not cause pain, such as a blanket, may become very painful when touching the skin. If the nerves send messages at incorrect times, one may experience muscle twitching or excessive sweating without activity. 

Peripheral neuropathies can be mild to disabling, depending on the type and severity of the damage, as well as the type of nerve fibers affected. Symptoms can develop over days, weeks, or months and, in mild cases, can often improve on their own without the need for treatment. Unlike the nerves in your central nervous system, peripheral nerve cells continue growing throughout your life, so it is possible to completely recover from some peripheral neuropathies, though it can take years to fully repair.

What Nerves Are Affected?

Which peripheral neuropathy you have depends on the number of nerves affected. With mononeuropathy, only one nerve is damaged, as you see with carpal tunnel syndrome. Multiple mononeuropathy, also known as mononeuropathy multiplex, features nerve damage to two or more nerves in different areas of the body. With polyneuropathy, most of the nerves in the PNS are damaged and symptoms are widespread, such as with Guillain-Barre syndrome.

Types of Peripheral Neuropathy

Peripheral neuropathies are divided into categories based on the type of nerves affected. In most cases, neuropathies affect all types of nerve fibers to some degree, however, they can be isolated to one category. Symptoms of peripheral neuropathy are determined by the type of nerves affected and will vary between individuals. There are three main classifications when it comes to peripheral neuropathies: motor, sensory, and autonomic.

• Motor Neuropathy – this affects the motor nerves that relay messages to your muscles that you control, such as for walking, picking up your morning cup of coffee, or talking to your friends.
• Sensory Neuropathy – the sensory nerves are responsible for touch and feelings, such as the pain you feel from a cut, changes in temperature, or feeling the touch of others.
• Autonomic Neuropathy – autonomic nerves work to regulate parts of your body that you do not consciously control, such as breathing, digestion, heart rate, and blood pressure.

Symptoms of Neuropathy

The symptoms experienced in people with neuropathy vary depending on the nerve type and the severity of the damage. Symptoms are also dependent on whether the damage affects the large or small nerve fibers. Large diameter fibers are insulated with myelin and damage to these nerves typically causes motor nerve symptoms but can contribute to some sensory symptoms as well. Small fibers do not have a myelin layer and most play a role in sensation and autonomic function. To better understand the symptoms’ differences, we have broken down the symptoms by nerve damage.

Motor Nerve Symptoms

The motor nerves are responsible for signaling your muscles for movement. When these nerves sustain damage, the most common symptom seen is muscle weakness. For example, muscle weakness in the legs may make walking difficult. Other symptoms associated with motor nerve damage include:

• Painful muscle cramps
• Involuntary muscle contractions (fasciculations)
• Decreased muscle tone
• Loss of deep tendon reflexes (the involuntary reflex that occurs with percussion of the tendon, such as when a clinician uses the percussion hammer on the patellar tendon below your kneecap to test for reflexes)

Depending on the neuropathy, progression of the disease can lead to muscle wasting, or atrophy, as is seen in multifocal motor neuropathy (MMN).

Sensory Nerve Symptoms

Sensory nerve symptoms differ depending on whether the damage affects the small or large nerve fibers. While damage to either fiber causes symptoms that are sensory in nature, they are slightly different, so we will break symptoms down based on fiber type.

Large Nerve Damage

• Decreased sensation to vibrations or touch
• Hands and feet may experience abnormal sensations, feeling as though the patient is wearing gloves or socks
• Loss of reflexes
• Problems with positional awareness – for example, you may be unable to sense where your foot is when walking, resulting in problems with mobility.

Small Nerve Damage

• Decreased sensation of pain in a concentrated area, such as a pinprick
• Increased sensitivity to general pain (hyperalgesia)
• Abnormal pain from stimulation that does not normally cause pain (allodynia) – for example, your bed sheets touching your skin can cause extreme pain
• Decreased temperature sensations
• Tingling, burning, and pain in toes and feet 
• Changes in cold or warm temperatures can provoke pain
• Symptoms worsen at night

Autonomic Nerve Symptoms

Symptoms for autonomic nerve dysfunction depend on the nerves involved but can affect multiple areas of the body and cause debilitating symptoms and conditions, including postural orthostatic tachycardia syndrome (POTS). Symptoms can affect the stomach and digestive system, the health and lungs, and the bladder. Some autonomic symptoms and conditions can include:

General Symptoms

• Lack of/excessive sweating
• Heat intolerance, often brought on by activity
• Sexual dysfunction (problems with erection for men and vaginal dryness and orgasm issues for women)
• Unexplained weight loss

Heart and Lung Symptoms

• High/low blood pressure, often with extreme changes occurring when standing
• Abnormal heart rate or rhythm
• Chest pain
• Dizziness/lightheadedness often occurs with positional changes
• Fainting
• Exhaustion/fatigue
• Shortness of breath with activity or exercise

Stomach and Digestive Symptoms

• Constipation
• Diarrhea
• Feeling full after only a few bites of food
• Nausea after eating
• Trouble controlling bowel movements
• Trouble swallowing
• Bloating
• Vomiting undigested food

Bladder Symptoms

• Difficulty starting urination
• Incomplete bladder emptying
• Leaking urine

Causes of Neuropathies 

Neuropathy is a very common condition and there are many different causes of nerve damage that contribute to them. While diabetes is the most common cause of neuropathy, there are many more causes including:

• Autoimmune disorders, such as lupus and rheumatoid arthritis
• Infections, such as HIV, Epstein Barr virus (EBV), and SARS-CoV-2
• Vitamin deficiencies
• Metabolic disease
• Heavy metal poisoning
• Thyroid conditions
• Nerve trauma
• Certain medications, such as those used for cancer and high blood pressure
• Pressure on the nerves, such as with carpal tunnel syndrome
• Excessive cold temperature exposure

Treatment Options for Neuropathy

Treatment for neuropathies depends on which nerves are affected and if they are caused by any underlying conditions. While some forms of neuropathy can be treated and, in some cases, cured, not all neuropathies are as easily managed. Treatments first focus on controlling the underlying condition, such as diabetes. Treatment then focuses on managing and controlling symptoms, as well as trying to prevent any further nerve damage. This can include medications, dietary changes, immune suppression or immune-modulating treatments, transcutaneous electrical nerve stimulations (TENS), or surgical intervention.

Neuropathies and Long COVID

Many Long COVID patients are experiencing varying forms of neuropathy as a major symptom. Two main neuropathic conditions that we are seeing occur with Long COVID include postural orthostatic tachycardia syndrome (POTS) and Guillain-Barre syndrome (GBS). In addition, Long COVID patients hospitalized during their acute infection may experience neuropathy as a result of prone-position bedding while in the ICU. Those with pre-existing diabetes before their acute case of COVID have a higher risk of developing neuropathies with Long COVID or experiencing a worsening of their pre-existing neuropathy.