Vision Problems After COVID: Causes and Treatment

ATHER  |  BRAIN INJURY AWARENESS November 9, 2022Medically Reviewed by Dr. Alina Fong Cognitive FX

When most people think of COVID-19 symptoms, they often recall the most common acute symptoms: brain fog, sore throat, congestion, headaches, and the like. What many don’t know is that long COVID can affect your vision for months after contracting the illness.

Current studies show that 1 in 10 COVID patients experience at least one eye problem, such as dryness, redness, blurred vision, or sensitivity to light. Conjunctivitis is common in the early stages of the illness, and for some patients, it’s the first sign of a COVID-19 infection. 

However, as we’ll discuss in this article, the real number of patients experiencing eye issues is likely higher, and the range of symptoms is much broader. Red and watery eyes are easy to spot, but it can be challenging for patients to recognize symptoms that stem from gaze and focus abnormalities. Some examples of potentially vision-related symptoms are headaches, difficulty focusing while reading, feeling overwhelmed in crowded spaces, dizziness while in a moving vehicle, and more. Because most research studies (a) rely on asking patients about their symptoms and (b) don’t include all of the appropriate tests to diagnose vision problems, many post-COVID vision changes go unreported. 

We also know that COVID patients don’t just experience vision problems. They also have a wide range of symptoms, from cognitive issues to digestive problems. The best approach to recovery for these patients is one that considers the whole person. It’s key that post-COVID patients find a provider who can address the wide range of effects long COVID has throughout the body and who is willing to diagnose the root issue (rather than treating just symptoms).

At Cognitive FX, we look at how the virus has affected your brain and body, then devise a plan to restore normal function. Our approach involves a combination of aerobic exercise and multidisciplinary therapies to address specific issues that you’re experiencing, including problems with your vision if you have them.  

n this article, we’ll look at:

Our treatment was originally designed to help post-concussion patients recover from persistent symptoms. After just one week of treatment, over 90% of our patients show improvement. Thus far, we’ve seen similar results with long COVID patients who pass our current screening criteria. To discuss your specific symptoms of COVID-19 and determine whether you’re eligible for treatment at our clinic, schedule a consultation.

Can COVID-19 Cause Vision Problems?

Soon after the coronavirus pandemic started in 2020, ophthalmologists worldwide started reporting how patients infected with the virus were experiencing visual symptoms during their illness. Common symptoms identified during these early stages included conjunctivitis, dry and itchy eyes, blurry vision, and sensitivity to light.  

However, over the past two years, the medical community and ophthalmology experts spotted a wider range of symptoms than previously expected, such as issues with saccades (how your eye switches focus from point to point), control of eye movements, and communication issues between the vestibular and visual systems. These issues are difficult for patients themselves to recognize and many doctors are not trained to look for and diagnose them. As a result, there are some misconceptions about the impact of COVID-19 on vision. 

When you think of problems with vision, you might think of people who need to wear glasses. Some see well at a distance but need glasses to see images that are near (hyperopia), while others can see objects that are near clearly but need glasses to see distant objects (myopia). Someone with 20/20 vision can see both near and far objects clearly and thus does not need glasses.

However, it’s possible to have vision-related changes triggered by COVID-19 and to still have 20/20 vision. Many vision problems don’t affect visual acuity. Patients’ eyes may not converge or diverge correctly. They might struggle with certain types of eye movement, experience reduced peripheral vision, not see clearly when they’re moving… the list of possible problems with your eyes is quite long. 

This brings us to our first misconception: Many patients believe that just because they haven’t noticed any problems with their vision that their eyes and visual system are functioning normally. In reality, it can be quite difficult to detect problems in your own vision because your brain does its best to compensate. 

Instead of noticing your eye problems, you’re more likely to experience the symptoms those eye problems result in: headaches, dizziness, nausea, difficulty concentrating, fatigue, and more. Most people are not aware of how the visual system can cause these symptoms, and they never think to seek help from a vision specialist. 

A second misconception is that vision problems caused by COVID-19 are rare. This is somewhat supported by clinical studies. Studies over the past two years found ocular manifestations in patients with COVID-19 ranging from 2% to 32%, with most results hovering around 10%

However, we believe the real value is much higher. Most of these studies only followed participants for a few weeks and looked for obvious symptoms like red and itchy eyes, which are easy to detect. Symptoms like problems with divergence (the ability to focus on a distant object) and convergence (the ability to focus on a close object) require specialized tests.

In addition, symptoms may not develop immediately and might come and go in waves like many other long COVID symptoms. To get a more accurate understanding of the situation, we need clinical studies which follow patients for more extended periods and which test for a wider range of symptoms. 

Vision Symptoms Caused by COVID-19

One of the most commonly reported eye conditions caused by COVID-19 in both children and adults is conjunctivitis (colloquially called pink eye). Some studies found that 9 in 10 patients with eye symptoms experience this condition. These patients often experience red and itchy eyes, dry eyes, watery eye discharge, sensitivity to light, and eye pain. In some cases, this eye condition may also cause blurry vision and swollen eyes. 

In addition to conjunctivitis, vision symptoms caused by COVID-19 may include the following:

  • Ocular irritation
  • Red eyes
  • Eye soreness
  • Blurry vision
  • Tunnel vision
  • Double vision
  • Vision loss
  • Floaters in the eyes
  • Cotton wool spots
  • Loss of peripheral vision
  • Uveitis (inflammation of the eye)
  • Eye infection
  • Swollen eyelids
  • Sensitivity to light
  • Glaucoma
  • Divergent and convergent issues
  • Saccades problems
  • Gaze fixation issues
  • Problems with focus
  • Vestibular-ocular deficiencies
  • Retinal artery occlusion and retinal vein occlusion caused by hemorrhage or blood clots

Causes of Vision Problems After COVID-19

There are many possible ways to explain how COVID-19 can cause vision problems. For most patients, it’s likely a mixture of multiple factors. Some of the most important reasons include…

  • Disruption of the Autonomic Nervous System (ANS)
  • Neurovascular Coupling (NVC) dysfunction
  • Direct impact on brain function related to vision
  • Vestibular issues
  • Pre-existing visual dysfunction
  • Side effects of medication
  • Blood clots
  • Direct viral attack on the eyes
  • Ventilators

Disruption of the Autonomic Nervous System (ANS)

We’ve discussed in a previous post how COVID-19 can disrupt the normal functioning of the autonomic nervous system (ANS). 

Along with other important functions like controlling heart rate and blood pressure, this part of the nervous system is also involved in vision. Specifically, it controls the movement of the iris to fine-tune the amount of light that enters the eye, similar to a camera aperture. 

The ANS has two important components: the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). Stimulation of the sympathetic branch, which triggers “fight or flight” responses when the body is under stress, induces pupil dilation. In contrast, stimulation of the parasympathetic system, known for “rest and digest” functions, causes the pupil to contract.

Under normal circumstances, SNS and PNS work in balance, and the size of the pupils change as needed. In COVID patients, however, the SNS tends to be dominant, which may cause some vision issues, such as light sensitivity and blurry vision. 

Neurovascular Coupling (NVC) Dysfunction

Vision problems can also occur if there’s a disruption in the way nerve cells receive the resources they need to function normally. Under normal circumstances, brain cells get nutrients and oxygen from a network of blood vessels. The dynamic relationship between blood vessels and the particular neuronal clusters they supply with resources is called neurovascular coupling (NVC). 

If this dynamic relationship is disrupted, affected regions of the brain may struggle to perform regular functions. Researchers have already established that COVID-19 can have a long-term impact on the brain. Recently, a study found damage in multiple brain regions over four months in elderly adults after they experienced a COVID infection. If you want to find out more, we have written about this important study in more detail in another post

It’s not unreasonable to think that if the virus affects function in the visual cortex — the primary region of the brain that receives and processes visual information — it can lead to vision problems such as poor visual acuity, loss of field of vision, and sensitivity to light.

If you notice that your vision gets worse during or after highly demanding cognitive tasks, it’s likely that you’re experiencing symptoms caused by NVC dysfunction. It’s also not unusual for the effects of NVC dysfunction to combine with ANS dysfunction. 

Vestibular Issues

Many COVID-19 patients also experience symptoms affecting the vestibular system, including dizziness, balance problems, and vertigo. A common complaint for these patients is that their vision is also affected. They can have problems focusing on objects or “seeing” objects moving from side to side. (There are evolving hypotheses linking COVID’s effect on the brainstem to these symptoms.)

This occurs because the vestibular system communicates with the eyes via an automatic function called the vestibulo-ocular reflex (VOR). The VOR is crucial to maintaining both balance and clear vision, controlling the position of the eyes so that when you move, you can keep your gaze stable and fixed on a certain point. However, if this system is not working properly due to a Sars-CoV-2 infection, patients may experience blurry or double vision, even though there’s nothing wrong specifically with the eyes. 

Pre-existing Visual Dysfunction

Some patients have vision problems they aren’t aware of which are then exacerbated by COVID-19. The brain does an amazing job of compensating for small problems in eye coordination and other visual issues. But if your brain is affected by COVID-19, it may not have enough bandwidth to compensate for those issues any longer. The result is a seemingly new set of vision problems when in reality, they just weren’t bad enough to cause symptoms until now.

Side-effects of Medication

Some commonly prescribed drugs can have adverse ocular effects. Some of these go away when the patient stops taking the medication, but others may cause irreversible vision loss.

This is particularly dangerous for COVID patients with diabetes, heart disease, and hypertension. For example, some medications for hypertension and diabetes cause abnormalities in pupil size, while some drugs for heart disease increase the risk of cataracts and cause eye irritation. The list of medications with a potential impact on vision includes steroids, antihistamines, antipsychotics, and any meds that affect blood flow. (Some research shows a large increase in the incidence of macular degeneration linked to blood pressure medication).

In addition, some antiviral medications can cause mild eye inflammation and redness, as well as blurry vision and ocular pain. However, there is no evidence that meds routinely used to treat most COVID-19 patients can cause vision problems. 

Our advice is to contact your physician or eye doctor if you experience any visual symptoms. Most symptoms are only mild, and you may feel that these problems are a reasonable trade-off for a potentially life-saving drug. Make sure you inform your doctor of all the medications you take, including prescription and over-the-counter, along with the dosages.

Other Possible Causes

Poor blood flow to the retina and corneaBlurred vision can result from the virus blocking, or at least restricting, the blood supply to the eye. This is known as retinopathy. Without nutrients and oxygen, the tissue in the retina may start to swell and die, making this area look white and fluffy, like cotton wool. These are commonly known as cotton wool spots and do not typically affect a person’s visual acuity, but may cause eye pain. 

Direct viral attack: The virus may be able to get into the body through the eyes. If SARS-CoV-2 reaches the surface of the eye, it can travel through the mucous membrane and eventually reach the retina all the way in the back of the eye. Expression of the ACE-2 receptor allows the virus to infect cells in the eye, which may explain many symptoms such as conjunctivitis, red and itchy eyes, and blurry vision. Given the connection between the eye and brain via the optic nerve, infection of the retina could be a way for the virus to reach the brain and cause further damage. 

Ventilators: It’s possible that COVID patients who suffered a severe COVID-19 infection develop vision problems after being on a ventilator. A study suggested that some patients on ventilators have nodules growing on the macula of the eye (this macular part processes what’s directly in front of the eyes), increasing the risk of conjunctivitis, vascular problems, and potential loss of vision. 

Treatment at Cognitive FX

Most long COVID patients who experience vision problems and eye disease also have a wide range of other symptoms, such as brain fog, difficulty sleeping, and headaches, to name just a few. Instead of looking at visual issues in isolation, our approach is to tackle the root of the problem and address multiple symptoms at the same time. 

Before treatment, you will undergo a detailed medical examination, allowing our doctors to find out more about your medical history and current symptoms. Part of our evaluation includes a functional Neurocognitive Imaging scan (fNCI) to identify which regions of the brain were affected by neurovascular coupling dysfunction and how well they’re communicating with other brain regions. The scan includes 56 areas of the brain. Using the information from the scan and the medical examination, our team will design a treatment plan custom-made for your needs. 

For example, this part of an fNCI report shows regions involved in reading comprehension, whether they are hypoactive (indicated a blue color on the report), and whether they’re communicating with each other as expected:

Results from a reading comprehension test and brain scan.

During our week-long treatment — called Enhanced Performance in Cognition, or EPIC for short— patients receive multidisciplinary therapy, including… 

  • Vision therapy
  • Neuromuscular therapy
  • Occupational therapy
  • Vestibular therapy
  • Cognitive therapy
  • Sensorimotor therapy
  • Neurointegration therapy
  • Psychotherapy
  • And more.

These therapies are appropriate therapeutic approaches for NVC dysfunction, autonomic dysfunction, vision problems, and vestibular issues. Some of the post-COVID symptoms these therapies can help resolve in addition to vision include…

All of our therapies have a visual component and will address some of your symptoms. However, we also have specific activities to rehabilitate your vision, such as the Brock string and Dynavision.

Our therapists use the Brock string for patients who are experiencing visual perception issues. This tool helps retrain the eyes to work together to focus on beads located at different distances along the string.

Dynavision is a computerized light board where patients push buttons as they light up, following different patterns on the board. The task may be as simple as hitting every button that lights up as quickly as possible, or it may be more challenging, where you only hit the green and avoid the red lights. This is a great tool to improve oculomotor coordination and for activating a number of brain regions involved in movement, cognition, and vision. 

Many of our patients experience significant improvements in just one week in many of their symptoms, but vision problems often need more than one week’s worth of therapy. It may take from six months to a year of vision therapy for your eyes to fully recover. We can refer you to a vision specialist in your hometown and show you how to do specific exercises at home. 

Our patients report a significant decrease in symptoms related to emotional function, sleep, concentration, clarity of thought, memory, and light sensitivity at the end of one week of treatment. 

While many other symptoms show direct improvement, they often require some rest at home or continuing therapy for a more marked improvement. Many patients are understandably tired after an intense week-long treatment protocol and experience less fatigue when they’re able to rest at home.

Percent symptom decrease based on 43 patient evaluations.

At the end of the week, you will receive a second fNCI scan to see how your brain is improving. Then, our clinicians will analyze your results and give you some homework, which typically includes aerobic exercise, cognitive games, and cognitive rest to help you continue your recovery journey at home.

Tips to Help You Cope With Vision Symptoms at Home

Not surprisingly, COVID long haulers with visual symptoms can experience difficulties with many activities during the day, including cooking, shopping, watching television, and reading. Here are a few tips to improve eye health and cope with your symptoms at home and work:

  • Follow the 20-20-20 rule: If your work involves long periods of the day in front of a computer or any other activities that rely heavily on your vision, you might suffer from mental fatigue, dry eyes, and headaches. Throughout the day, take a 20-second break away from the computer every 20 minutes and focus on an object about 20 feet away from you. This is a quick and easy exercise to reduce eye strain. Also, limit screen time as much as possible. 
  • Palming to relax your eyes: Cup your hands and apply gentle pressure over the sockets of your eyes for about 30 seconds. Close your eyes and breathe deeply. You can repeat this exercise throughout the day to relax your eyes. For your eye care routine, you may also find it helpful to apply eye drops (but avoid overuse). 

COVID-19 inflammation results in urine cytokine elevation and causes COVID-19 associated cystitis (CAC)

Authors: Laura E Lamb 1Nivedita Dhar 2Ryan Timar 3Melissa Wills 3Sorabh Dhar 4Michael B Chancellor 5 PMID: 33213997 PMCID: PMC7644255 DOI: 10.1016/j.mehy.2020.110375

Abstract

Coronavirus disease 2019 (COVID-19) causes a wide range of symptoms, including several unexpected symptoms such as loss of taste, skin changes, and eye problems. We recently observed patients with documented COVID-19 develop de novo severe genitourinary symptoms, most notably urinary frequency of ≥ 13 episodes/24 h and nocturia ≥ 4 episodes/night. We call these associated urinary symptoms COVID-19 associate cystitis (CAC). COVID-19 severity is associated with inflammation. We collected urine samples from COVID-19 patients, including patients with CAC, and found elevation of proinflammatory cytokines also in the urine. It has been previously shown that patients with urinary incontinence and ulcerative interstitial cystitis/bladder pain syndrome have elevated urinary inflammatory cytokines compared to normal controls. We therefore hypothesize that CAC, with presentation of de novo severe urinary symptoms, can occur in COVID-19 and is caused by increased inflammatory cytokines that are released into the urine and/or expressed in the bladder. The most important implications of our hypothesis are: 1) Physician caring for COVID-19 patients should be aware of COVID-19 associate cystitis (CAC); 2) De novo urinary symptoms should be included in the symptom complex associated with COVID-19; and 3) COVID-19 inflammation may result in bladder dysfunction.

Patients with COVID-19 develop new, worsening overactive bladder symptoms

Authors: Maria Marabito American Urological Association 9/15/2021

Patients with COVID-19 reported experiencing severe genitourinary symptoms during infection, and new or worsening overactive bladder symptoms after recovery, according to recent findings from two studies.

The data were presented at the American Urological Association meeting.

Overactive bladder symptom scores.
Chen W, et al. MP63-02: New or worsening overactive bladder symptoms after recovery from COVID-19. Presented at: American Urological Association meeting; Sept. 10, 2021 (virtual meeting).

During infection

Michael B. Chancellor, MD, a professor of urology at Oakland University Beaumont School of Medicine, and colleagues conducted a study to determine whether genitourinary symptoms were associated with pro-inflammatory cytokines in the urine of patients with COVID-19. The analysis included 53 patients with normal renal function who were hospitalized for COVID-19 and 12 asymptomatic control patients. The researchers assessed patients with an AUA Urology Care Foundation Overactive Bladder (OAB) Assessment Tool to determine their urinary symptoms based on a scale of 0 to 25, with increasing scores representing increasing severity. They also collected urine samples from patients, which were then tested for SARS-CoV-2 and pro-inflammatory cytokines. Patients’ median age was 64.5 years.

The median total OAB symptom score among patients with COVID-19 was 18, with a range from four to 21. Quality of life scores ranged from eight to 24, with a median of 19; higher scores related to better quality of life. Patients with symptoms of COVID-19-associated cystitis experienced increased urinary urgency, frequency, nocturia and pain as well as worsening quality of life, according to Chancellor.

The researchers found that most patients with COVID-19 did not have the virus in their urine. However, levels of inflammatory cytokines, including interleukin-6, IL-10, GRO/CXCL and C-reactive protein, were significantly increased in patients with COVID-19. These cytokines may correlate with severity and duration of COVID-19 infection, Chancellor said.

“In conclusion, our study shows that COVID-19 can have de novo and severe genitourinary symptoms that are highly bothersome,” Chancellor said during a prerecorded presentation.

The symptoms experienced by patients with COVID-19 fall under the umbrella of OAB, Suzette E, Sutherland, MD, director of female urology at the University of Washington and moderator of the presentation, noted.

After recovery

In a separate study, Nivedita Dhar, MD, a urologist at the DMC Medical Group in Michigan, and colleagues assessed OAB symptoms after patients recovered from COVID-19. Using the same OAB Assessment Tool, the researchers collected symptom and quality of life scores among patients who were recovering from COVID-19 in a hospital between May 22, 2020, and Dec. 31, 2020. The median age of patients was 64.5 years and the median length of stay in the hospital was 10 days.

Dhar and colleagues identified 350 patients with new or worsening OAB symptoms. In patients with a new onset of OAB symptoms, the median symptom score was 18. Individuals with worsening OAB symptoms had a median score of 8 before developing COVID-19 and a median score of 19 after recovery, according to the data. Meanwhile, the median quality of life score among all patients was 19. In those with worsening OAB, the median quality of life score before COVID-19 was 9 compared with a score of 20 after recovery.

Dhar and colleagues concluded that the exacerbation of OAB symptoms following COVID-19 “was evident by increases in symptom severity scores and deteriorating quality of life.” The pathophysiological mechanisms remain unknown, they added.

Additional research is needed to assess the potential role of COVID-19-associated cystitis in long COVID, Chancellor said.

References:

Chancellor MB, et al. MP29-15: COVID-19 associated cystitis (CAC): increased urinary symptoms and biomarkers of inflammation in urine in patients with acute COVID-19. Presented at: American Urological Association meeting; Sept. 10, 2021 (virtual meeting).

Hypoglossal Nerve Palsy Following COVID-19 Vaccination in a Young Adult Complicated by Various Medicines

Authors: Tatsuhiko OkayasuRyuichi OhtaFumiko YamaneSatoshi AbeChiaki Sano

 September 15, 2022 (see history) DOI: 10.7759/cureus.29212 Cite this article as: Okayasu T, Ohta R, Yamane F, et al. (September 15, 2022) Hypoglossal Nerve Palsy Following COVID-19 Vaccination in a Young Adult Complicated by Various Medicines. Cureus 14(9): e29212. doi:10.7759/cureus.29212

Abstract

Mononeuritis multiplex is a rare form of cerebral nerve palsy caused by various factors. Coronavirus disease 2019 (COVID-19) vaccination could be an etiology of mononeuritis multiplex, which can affect various nerves. Post-COVID-19 and vaccination-related neurological impairments involve cranial nerves such as the facial, trigeminal, and vagal nerves. We report our experience with a 34-year-old man who developed hypoglossal nerve palsy following COVID-19 vaccination, complicated by progressive mononeuritis multiplex. Hypoglossal nerve palsy may occur following COVID-19 vaccination. The symptoms vary and may progress without treatment. Physicians should consider the possibility of mononeuritis multiplex after COVID-19 vaccination and provide prompt treatment for acute symptom progression.

Introduction

Mononeuritis multiplex is a rare form of cerebral nerve palsy caused by various factors, as the etiologies, infection, and autoimmunity are common. Herpes zoster and simplex are the predominant infections in the category of infection [1,2]. Among autoimmune causes, small-to-medium-sized vasculitis, such as an antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and Sjogren’s syndrome, are common [1,2]. The progression of mononeuritis multiplex symptoms varies depending on the human body’s etiology and immunological reactions [3,4]. Severe cases may involve multi-extremity paralysis, which should be treated with intravenous immunoglobulin therapy, steroids, and plasma exchange, according to the etiology [2,5]. Thus, effective treatment requires the detection of etiology and rapid treatment.

COVID-19 and COVID-19 vaccinations are also potential etiologies of mononeuritis multiplex, which can affect various nerves. Based on previous reports, post-COVID-19 and vaccination-related neurological impairments involve cranial nerves such as the facial, trigeminal, and vagus nerves [6-8]. However, there are few reports of mononeuritis multiplex following COVID-19 vaccination. Here, we report a case of mononeuritis multiplex that spread from the right hypoglossal nerve to the right hand and leg. The progression was acute, and the patient required treatment with intravenous immunoglobulin and steroid pulse therapy. Various complications occurred during the clinical course, and the treatment course was complicated. Our case demonstrates the importance of a clinical diagnosis of mononeuritis multiplex with prompt treatment and approaches to reduce long-term complications.

Case Presentation

A 34-year-old man was admitted to our hospital with a chief complaint of dysphasia and difficulty speaking. Ten days before admission, the patient had received the third vaccination for COVID-19. He had a fever of >38 °C one day after vaccination. Seven days before admission, he experienced tingling on the right side of his tongue, followed by dysphagia and difficulty speaking. These symptoms progressed, and the patient noticed that the right side of his tongue had shrunk; therefore, he visited our hospital. He had a past medical history of varicella-zoster virus infection in the first branch of the left trigeminal nerve and had been treated with valaciclovir. The patient did not take any regular medication.

His vital signs at admission were as follows: blood pressure, 114/59 mmHg; pulse rate, 78 beats/min; body temperature, 36.9 °C, respiratory rate, 15 breaths/min; and oxygen saturation, 97% on room air. He was alert to time and place. Physical examination showed that the right half of his tongue was atrophied and shifted to the right during the prostration.

No other abnormal neurological findings were noted. There were no obvious abnormalities in the chest or abdomen and no skin eruptions. Physical examination revealed right hypoglossal nerve palsy; thus, viral infection, brain stroke, brain tumor, meningitis, ANCA-related vasculitis, and Guillain-Barre syndrome was suspected. Blood tests, head magnetic resonance imaging (MRI), head computed tomography (CT), and lumbar puncture were performed. The results were within normal limits (Table 1).

MarkerLevelReference
White blood cells6.83.5–9.1 × 103/μL
Neutrophils5144.0–72.0%
Lymphocytes32.918.0–59.0%
Monocytes80.0–12.0%
Eosinophils6.90.0–10.0%
Basophils1.20.0–3.0%
Red blood cells5.343.76–5.50 × 106/μL
Hemoglobin1611.3–15.2 g/dL
Hematocrit47.833.4–44.9%
Mean corpuscular volume89.579.0–100.0 fl
Platelets24.613.0–36.9 × 104/μL
Total protein6.96.5–8.3 g/dL
Albumin4.43.8–5.3 g/dL
Total bilirubin0.50.2–1.2 mg/dL
Aspartate aminotransferase188–38 IU/L
Alanine aminotransferase274–43 IU/L
Alkaline phosphatase80106–322 U/L
γ-Glutamyl transpeptidase50<48 IU/L
Lactate dehydrogenase165121–245 U/L
Blood urea nitrogen13.98–20 mg/dL
Creatinine0.660.40–1.10 mg/dL
eGFR≥90> 60.0 mL/min/1.73 m2
Serum Na137135–150 mEq/L
Serum K3.93.5–5.3 mEq/L
Serum Cl10198–110 mEq/L
Serum P3.12.7–4.6 mg/dL
Serum Mg21.8–2.3 mg/dL
CK11256–244 U/L
CRP0.07<0.30 mg/dL
Artery blood gas analysis  
pH7.4187.35–7.45 
PCO242.535.0–45.0 mmHg
PO289.375.0–100.0 mmHg
HCO326.920.0–26.0 mmol/L
Lactate1.20.5–1.6 mmol/L
Cerebrospinal fluid testing  
Colorclear 
Cell count10–5 /μL
Protein3615–45 mg/dL
Glucose5748–83 mg/dL
Chloride126.5113–128 mEq/L
Table 1: Initial laboratory data of the patient

eGFR: estimated glomerular filtration rate; CK: creatine kinase; CRP: C-reactive protein

A videoendoscopic examination of swallowing was performed to evaluate dysphagia, with no obvious problems associated with swallowing function. Since the difficulty in moving the tongue and the white coating was remarkable, the patient was referred to a dental and oral surgeon to rule out tongue cancer.

Because the patient had a history of herpes zoster, we also considered viral reactivation and prescribed acyclovir (1500 mg/day) and prednisolone (60 mg/day) from the second day of admission. However, lumbar pain and headache appeared on day four of admission, for which epidural hematoma after lumbar puncture was suspected. Plain lumbar magnetic MRI and head CT showed edematous findings around both kidneys, clinically suggesting the possibility of acute kidney injury due to acyclovir. As the patient tested negative for varicella virus, acyclovir was discontinued (Figure 2).

Edematous-findings-around-both-kidneys-(blue-arrows)
Figure 2: Edematous findings around both kidneys (blue arrows)

On the seventh day of illness, weakness of the right upper and lower extremities and a Romberg’s sign was observed. Plain MRI of the upper arm and nerve conduction velocity tests were performed to investigate the cause, with no positive findings. Blood tests were negative for syphilis, hepatitis, HIV, ANCA, antinuclear antibody, and IgG4. Therefore, a clinical diagnosis of mononeuritis multiplex after administering the COVID-19 vaccine was made. On day seven of admission, prednisolone (60 mg/day), intravenous immunoglobulin (0.4 g/kg/day for five days), and methylprednisolone (1 g/day for three days) were initiated after consultation with a neurology physician. On day nine of admission, muscle pain, and general malaise developed immediately after intravenous methylprednisolone administration. As intravenous methylprednisolone could be the cause, the administration was discontinued, and oral prednisolone (60 mg/day) was started. Subsequently, a tingling pain appeared on the right scalp. He was treated with valacyclovir (3 g/day for one week). Dysphagia and extremity weakness gradually improved after rehabilitation. On day 14, after admission, the patient was transferred to a university hospital for further investigation and advanced rehabilitation.

Discussion

This case showed the possibility of hypoglossal nerve palsy as a rare complication of COVID-19 vaccination, specific neurological complications following COVID-19 vaccination, and the rapid treatment of mononeuritis multiplex to prevent symptom progression.

The relationship between the COVID-19 vaccine and mononeuritis multiplex has been discussed in various studies. Several case reports have shown an increased risk of mononeuritis multiplex within a few days to months after COVID-19 vaccination [8,9]. A review of COVID-19 vaccination also showed that most symptoms related to mononeuritis multiplex were mild and disappeared naturally [10]. However, some cases show severe symptoms that affect the patient’s activities of daily life and require intensive treatment [7,11]. Our patient initially had mild symptoms and did not require treatment for his vital symptoms. However, within one week, the symptoms progressed drastically from the tongue to the extremities, causing difficulties in walking. The clinical course of mononeuritis multiplex varies, and some cases caused by vasculitis from autoimmune and infectious diseases may be progressive [5,12]. Precise follow-up and prompt treatment with intravenous immunoglobulins and steroids should be initiated to prevent disease progression.

Hypoglossal nerve palsy could be a rare symptom following COVID-19 vaccination and warrants further investigation in future studies. Among the complications of COVID-19 vaccination, various neurological complications were reported in 2020 [9,10]. Guillain-Barre syndrome is a well-known but rare complication of COVID-19 vaccination and appears a few weeks after vaccination [13]. Other cranial nerves may also be involved in the complications of COVID-19. Several case reports and reviews have reported facial palsy, the pain of the trigeminal and facial nerves, and diplopia of the oculomotor nerves [10,14]. However, hypoglossal nerve palsy is rare, and its pathophysiology remains unclear. In the present case, the initial finding was difficulty in tongue movement caused by palsy of the hypoglossal nerves, which led to systemic neurological symptoms. Clinicians should consider assessing single cranial symptoms following COVID-19 because of the possible spread of multiple nerve symptoms, causing a decreased quality of life.

The COVID-19 pandemic may persist in the future; therefore, preventable measures are vital. Vaccination is a critical measure for prevention. Although various complications have been reported, they are rare; therefore, vaccination should be promoted [15,16]. However, the possible symptoms following COVID-19 vaccination should be appropriately described, and help-seeking behaviors (HSB) to medical facilities should be facilitated, especially in rural contexts lacking healthcare resources [17-19]. The patient in the present case was younger, but the duration of his visit to the hospital was nearly two weeks. Early treatment could have prevented symptom progression [14]. When the same symptoms occur in older patients, HSB varies and is challenging, causing a greater delay in treatment. Citizens and healthcare professionals should be educated regarding responses to symptoms following vaccination, and information provision should be promoted [20].

Conclusions

Hypoglossal nerve palsy may be a symptom of COVID-19 vaccination. The symptoms vary and may progress without treatment. Physicians should consider the possibility of mononeuritis multiplex after COVID-19 vaccination and provide prompt treatment for acute symptom progression.


References

  1. Mutluay B, Koksal A, Karagoz N, et al.: Early detection of mononeuritis multiplex & diagnosis of systemic diseases thru electrophysiological work out with polyneuropathy as preceeding symptom. J Neurol Sci. 2015, 357:341. 10.1016/j.jns.2015.08.1212
  2. Ghazaei F, Sabet R, Raissi GR: Vasculitic mononeuritis multiplex may be misdiagnosed as carpal tunnel syndrome. Am J Phys Med Rehabil. 2017, 96:e44-7. 10.1097/PHM.0000000000000562
  3. Marques IB, Giovannoni G, Marta M: Mononeuritis multiplex as the first presentation of refractory sarcoidosis responsive to etanercept. BMC Neurol. 2014, 14:237. 10.1186/s12883-014-0237-5
  4. Tanemoto M, Hisahara S, Hirose B, et al.: Severe mononeuritis multiplex due to rheumatoid vasculitis in rheumatoid arthritis in sustained clinical remission for decades. Intern Med. 2020, 59:705-10. 10.2169/internalmedicine.3866-19
  5. Tokonami A, Ohta R, Katagiri N, Yoshioka N, Yamane F, Sano C: Autoimmune vasculitis causing acute bilateral lower limb paralysis. Cureus. 2022, 14:e27651. 10.7759/cureus.27651
  6. Enrique E-R, Javier B, Hernando R, Herney Andrés G: Mononeuritis multiplex associated with SARS-CoV2-COVID-19 infection: case report. Int J Neurol Neurother. 2020, 7:102. 10.23937/2378-3001/1410102
  7. Needham E, Newcombe V, Michell A, et al.: Mononeuritis multiplex: an unexpectedly frequent feature of severe COVID-19. J Neurol. 2021, 268:2685-9. 10.1007/s00415-020-10321-8
  8. Andalib S, Biller J, Di Napoli M, et al.: Peripheral nervous system manifestations associated with COVID-19. Curr Neurol Neurosci Rep. 2021, 21:9. 10.1007/s11910-021-01102-5
  9. Taga A, Lauria G: COVID-19 and the peripheral nervous system. A 2-year review from the pandemic to the vaccine era. J Peripher Nerv Syst. 2022, 27:4-30. 10.1111/jns.12482
  10. Finsterer J, Scorza FA, Scorza C, Fiorini A: COVID-19 associated cranial nerve neuropathy: A systematic review. Bosn J Basic Med Sci. 2022, 22:39-45. 10.17305/bjbms.2021.6341
  11. Oaklander AL, Mills AJ, Kelley M, Toran LS, Smith B, Dalakas MC, Nath A: Peripheral neuropathy evaluations of patients With prolonged long COVID. Neurol Neuroimmunol Neuroinflamm. 2022, 9:10.1212/NXI.0000000000001146
  12. Abdelhakim S, Klapholz JD, Roy B, Weiss SA, McGuone D, Corbin ZA: Mononeuritis multiplex as a rare and severe neurological complication of immune checkpoint inhibitors: a case report. J Med Case Rep. 2022, 16:81. 10.1186/s13256-022-03290-1
  13. Raahimi MM, Kane A, Moore CE, Alareed AW: Late onset of Guillain-Barré syndrome following SARS-CoV-2 infection: part of ‘long COVID-19 syndrome’?. BMJ Case Rep. 2021, 14:10.1136/bcr-2020-240178
  14. Hasan I, Saif-Ur-Rahman KM, Hayat S, et al.: Guillain-Barré syndrome associated with SARS-CoV-2 infection: A systematic review and individual participant data meta-analysis. J Peripher Nerv Syst. 2020, 25:335-43. 10.1111/jns.12419
  15. Machida M, Nakamura I, Kojima T, et al.: Acceptance of a COVID-19 vaccine in Japan during the COVID-19 pandemic. Vaccines (Basel). 2021, 9:10.3390/vaccines9030210
  16. García-Montero C, Fraile-Martínez O, Bravo C, et al.: An updated review of SARS-CoV-2 vaccines and the importance of effective vaccination programs in pandemic times. Vaccines (Basel). 2021, 9:10.3390/vaccines9050433
  17. Cornally N, McCarthy G: Help-seeking behaviour: a concept analysis. Int J Nurs Pract. 2011, 17:280-8. 10.1111/j.1440-172X.2011.01936.x
  18. Ohta R, Ryu Y, Sano C: Older people’s help-seeking behaviors in rural contexts: A systematic review. Int J Environ Res Public Health. 2022, 19:10.3390/ijerph19063233
  19. Shaw C, Brittain K, Tansey R, Williams K: How people decide to seek health care: a qualitative study. Int J Nurs Stud. 2008, 45:1516-24. 10.1016/j.ijnurstu.2007.11.005
  20. Ohta R, Ryu Y, Kitayuguchi J, Sano C, Könings KD: Educational intervention to improve citizen’s healthcare participation perception in rural Japanese communities: A pilot study. Int J Environ Res Public Health. 2021, 18:10.3390/ijerph18041782

Autopsy-Based Pulmonary and Vascular Pathology: Pulmonary Endotheliitis and Multi-Organ Involvement in COVID-19 Associated Deaths

Authors: artina Haberecker University Hospital Zürich Esther I Schwarz University of Zurich Peter Steiger University of Zurich Karl Frontzek University of ZurichSeptember 2021 Respiration 101(2):1-11 DOI:10.1159/000518914License CC BY-NC 4.0

Abstract and Figures

Background: Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (CO-VID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology. Methods: Fifteen SARS-CoV-2 positive autopsies with clinically distinct presentations (age 22-89 years) were retrospectively analyzed with focus on vascular, thromboembolic, and ischemic changes in pulmonary and in extrapulmonary sites. Eight patients died due to COVID-19 associated respiratory failure with diffuse alveolar damage in various stages and/or multi-organ failure, whereas other reasons such as cardiac decompensation, complication of malignant tumors, or septic shock were the cause of death in 7 further patients. The severity of gross and histopathological changes was semi-quantitatively scored as 0 (absent), 1 (mild), and 3 (severe). Severity scores between the 2 groups were correlated with selected clinical parameters, initial chest imaging, autopsy-based cause of death, and compared using Pearson χ2 and Mann-Whitney U tests. Results: Severe pulmonary endotheliitis (p = 0.031, p = 0.029) and multi-organ involvement (p = 0.026, p = 0.006) correlated significantly with COVID-19 associated death. Pulmonary microthrombi showed limited statistical correlation, while tissue necrosis, gross pulmonary embolism, and bacterial superinfection did not differentiate the 2 study groups. Chest imaging at hospital admission did not differ either. Conclusions: Extensive pulmonary endotheliitis and multi-organ involvement are characteristic autopsy features in fatal CO-VID-19 associated deaths. Thromboembolic and ischemic events and bacterial superinfections occur frequently in SARS-CoV-2 infection independently of outcome.

Histological vascular and gross pulmonary vascular findings in SARS-CoV-2 positive autopsies. Images demonstrate severe grade of vascular changes (larger involved areas and high number of foci) (a-d), images show mild grade morphological changes (smaller or only scattered areas involved) (e-h). Numerous (a) and only scattered (e) lymphocytes beneath the endothelium. Multiple middle-and small-sized (b and c) and only scattered small-sized peripheral (f, g) fibrin and leucocytic thrombi. Large multiple areas (d) and only small foci (h) of pulmonary hemorrhagic infarction and consolidation. a-g: H & E stain. b (inset): modified Picro-Mallory stain. H&E, hematoxylin and eosin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Histological vascular and gross pulmonary vascular findings in SARS-CoV-2 positive autopsies. Images demonstrate severe grade of vascular changes (larger involved areas and high number of foci) (a-d), images show mild grade morphological changes (smaller or only scattered areas involved) (e-h). Numerous (a) and only scattered (e) lymphocytes beneath the endothelium. Multiple middle-and small-sized (b and c) and only scattered small-sized peripheral (f, g) fibrin and leucocytic thrombi. Large multiple areas (d) and only small foci (h) of pulmonary hemorrhagic infarction and consolidation. a-g: H & E stain. b (inset): modified Picro-Mallory stain. H&E, hematoxylin and eosin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

Figures – available via license: Creative Commons Attribution-NonCommercial 4.0 International

Content may be subject to copyright.

Covid Linked To Disorder That Causes Sudden Vision Loss, Study Says

Authors: Zachary Snowdon Smith Forbes Apr 14, 2022

Covid-19 infection is linked to eye conditions called retinal vascular occlusions—blockages of blood vessels in the eye that can cause vision loss—according to a study published Thursday by JAMA Ophthalmology that threw light on one of several little-understood long-term effects of the virus.

KEY FACTS

The first condition, called retinal artery occlusions, can cause sudden blurring or loss of vision in one eye, and was found to have increased 29.9% in the period two to 26 weeks after Covid-19 diagnosis compared to the period 26 to two weeks before diagnosis, researchers concluded.

The second condition, retinal vein occlusions, causes similar symptoms to retinal artery occlusions and was even more strongly associated with Covid-19, with a 47% increase in the period two to 26 weeks after Covid-19 diagnosis compared to the period 26 to two weeks before diagnosis, according to the study.

The strong association between Covid-19 and retinal vein occlusions seems to confirm previous research suggesting that Covid-19 generally affects veins more severely than arteries, researchers said—a finding that could help guide treatment approaches for Covid-19 patients.

Even following Covid-19 infection, retinal vascular occlusions remained rare, with retinal artery occlusions affecting about 1 in 333,333 patients and retinal vein occlusions affecting about 1 in 81,967 patients during the period two to 26 weeks after they were diagnosed.

Researchers did not find that Covid-19 patients who were hospitalized were more likely to experience retinal vascular occlusions than those who were not hospitalized.

The study included 432,515 patients without a history of retinal vascular occlusions more than six months prior to their Covid-19 diagnosis, and who were diagnosed with the virus between January 20, 2020 and May 31, 2021.

TANGENT

Retinal vascular occlusions are caused when blood clots or fat deposits block blood vessels in the retina, the part of the eye that receives light and transmits images to the brain. These occlusions may cause damage ranging from slight vision impairments to whole-eye vision loss. Retinal artery occlusion is linked to diabetes, high blood pressure, elevated levels of fat in blood and various disorders affecting the heart or the carotid artery, according to the National Library of Medicine’s MedlinePlus service. Retinal vein occlusion is linked to diabetes, high blood pressure, fatty buildup in the arteries and eye disorders like glaucoma. Outcomes are variable: while many patients regain a degree of vision, there are no reliable treatments for whole-eye vision loss due to a retinal vascular occlusion. These occlusions may indicate the presence of clots or fat deposits elsewhere in the body, warning of a risk of stroke, according to Johns Hopkins Medicine.

KEY BACKGROUND

Though Covid-19’s immediate symptoms have been well documented, scientists have struggled to understand the longer-term effects of the virus. A study published Monday by JAMA Neurology determined that the long-term smell loss reported by some Covid-19 patients is tied to damage to the olfactory bulb, the part of the brain that processes smells. Covid-19 has also been associated with a range of vascular issues such as inflammation of the heart muscle or the sac containing the heart. Some researchers have concluded that much of the damage caused by the coronavirus is not directly inflicted by the virus itself, but by infection symptoms like inflammation, the New York Times reports. The authors of the JAMA Ophthalmology study suggested a similar interpretation, theorizing that the initial vascular damage caused by Covid-19 infection might make some people more vulnerable to a pre-existing risk of retinal vascular occlusions.

CONTRA

It’s possible that the JAMA Ophthalmology study underestimated the risk of retinal vascular occlusions among severely ill patients because those patients’ conditions may have prevented them from informing healthcare staff of vision changes, researchers said.

WHAT WE DON’T KNOW

Further research would be necessary to establish a cause-and-effect relationship between Covid-19 infection and retinal vascular occlusions, researchers said. The JAMA Ophthalmology study established only an association between the two conditions.

Risk of rare heart inflammation may be higher after Moderna than Pfizer COVID vaccine

Authors: ry Van Beusekom | News Writer | CIDRAP News  |  Nov 08, 202

Myocarditis and pericarditis are rare after mRNA COVID-19 vaccination, but rates of the inflammatory heart conditions were twofold to threefold higher after receipt of the second dose of the Moderna vaccine than after the Pfizer/BioNTech formulation, suggests a head-to-head comparison in Canadian adults.

The findings of the observational, population-based analysis were published yesterday in the Journal of the American College of Cardiology.

Researchers from the British Columbia Centre for Disease Control in Vancouver led the study on the diagnosis of myocarditis, pericarditis, or myopericarditis during a hospitalization or emergency department visit within 21 days after receipt of the second mRNA COVID-19 vaccine dose from Jan 1 to Sep 9, 2021. During that period, more than 870,000 Moderna and 2.2 million Pfizer second doses were administered in British Columbia.

Myocarditis is inflammation of the heart muscle, pericarditis is inflammation of the membrane surrounding the heart, and myopericarditis is an extension of pericardial inflammation into the heart muscle.

Risk after COVID infection higher

Rates of myocarditis (31 cases; 35.6 per million second doses) and pericarditis (20; 22.9 per million) were higher after the Moderna vaccine than after Pfizer (28; 12.6 per million and 21; 9.4 per million, respectively). For comparison, rates of myocarditis in the general population during the same period were 2.0 per million in vaccinees 18 to 39 years old and 2.2 per million in older adults.

Relative to the Pfizer vaccine, Moderna was tied to significantly higher chances of myocarditis (adjusted odds ratio [aOR], 2.78; 95% CI, 1.67 to 4.62), pericarditis (aOR, 2.42; 95% CI, 1.31 to 4.46), and myopericarditis (aOR, 2.63; 95% CI, 1.76 to 3.93). The link between Moderna and myocarditis was strongest for men (aOR, 3.21; 95% CI, 1.77 to 5.83) and the younger age-group (aOR for 18 to 39 years, 5.09; 95% CI, 2.68 to 9.66).

A person choosing an mRNA vaccine should “consider the self-limiting and mild nature of most myocarditis events, benefits provided by vaccination, higher effectiveness of the Moderna vaccine against infection and hospitalization [found in prior studies], and the apparent higher risk of myocarditis following COVID-19 infection than with mRNA vaccination,” lead author Naveed Janjua, MBBS, PhD, said in an American College of Cardiology news release.

In a related commentary, Guy Witberg, MD, MPH, and Ilan Richter, MD, MPH, both of Rabin Medical Center in Petah-Tikva, Israel, said the study provides further evidence that heart inflammation is rare after both vaccines.

It “should help put to rest ‘vaccine hesitancy’ due to concerns over cardiac adverse events,” they wrote. “Its results have practical policy implications: for a substantial segment of the population suffering from cardiovascular disease, especially those with left ventricular dysfunction, in whom minimizing risk of myocardial insult is crucial, these data give a strong argument to preferentially use the BNT162b2 [Pfizer] vaccine over mRNA-1273 [Moderna].”

Do COVID-19 and long COVID affect the bladder? Here’s what you should know

Written by: PROFESSOR VIK KHULLAR Published: 17/02/2022 Top Doctors

What is currently known about COVID-19’s effect on the bladder? What symptoms have been reported?

In the initial stages of the pandemic, the main symptom appeared to be a painful bladder, but over time, we have seen more and more patients with urinary frequencypain if they do not pass urine, or a desperate need to pass urine.

Another key element of what is now known as ‘COVID bladder’ is that patients will wake at night to pass urine. Patients who would only generally have one to two urine infections per year are now suddenly suffering from continuous and frequent infections.

COVID bladder has also resulted in patients arriving home with an intense urgency to pass urine, and they will often leak due to not being able to wait when unlocking their front door. Associated with that are long-COVID symptoms that generally include the following:

  • intolerance to food
  • fatigue
  • swelling without any reason
  • skin rashes
  • worsening in diarrhoea and/or constipation
  • dizziness when standing
  • fast heartbeat

Interestingly, important data and research on this has shown that there are certainly abnormalities in white blood cells. These white blood cells seem to decline in people who have long COVID. We have looked at the bladder and we have found declining white cells living in the bladder.

So, the reason why there seems to be less of these white blood cells when we carry out blood tests is that they are going into the tissues, causing inflammation and making everything very irritated.

Another thing that people find quite distressing with COVID bladder is that they will often feel quite anxious. Studies have really shown that COVID bladder can actually affect all parts of the body. Interestingly, the vast majority of patients who have reported these COVID bladder-related symptoms have only suffered from a mild bout of COVID-19.

What is the connection between these symptoms and the COVID-19 virus?

The key thing about these symptoms is that, first of all, what has happened is that doctors who have been investigating have been doctors dealing with the lungs or blood pressure. It is only when we look at the areas which are affected, that, on one hand, there are lung-related symptoms such as difficulty breathing when walking up the stairs.

In terms of the heart, often people will have POTS. This means the person will feel very dizzy when standing, and their heart beats very fast to try and keep the blood pressure up. Both the lungs and heart are related to something called the autonomic nervous system, which is the part of the nervous system that gets involved when people have infections.

We have all experienced a cold before and thought to ourselves “I should be able to sit at my desk and work”, but people suffering from COVID bladder have said that they just feel so ill that they have got to go to bed. Now, the reason they have to go to bed is that their blood pressure is low, the pulse is high, and they have to, by lying down, correct the blood pressure, and as a result, they feel much better.

This is a very normal response to infection, and patients should not be concerned when the body causes these symptoms which affect the heart and the breathing. All of these symptoms are actually responses of the immune system to an infection. What is interesting about COVID-19, however, is that it makes one part of the immune system very angry.

This angry part of the immune system is typically also seen when someone gets a mosquito bite. Nothing much happens in terms of the bite itself, but 24 hours later we see swelling, redness, and pain. We see a similar thing in patients with long COVID, who report muscle pain. It is almost as if the body is experiencing a mosquito bite. People will also describe a feeling of being poisoned, but this is a normal feeling as the body is trying to fight off the virus, even if the virus may not be there anymore.

If a person has these symptoms, what should they do?

There are long COVID clinics where patients can be assessed. Patients will often have a low-grade bladder infection. The body has decided that the virus is in the body, the body has then produced inflammation, and this inflammation has then affected the inside of the bladder. We have now looked at over 60 patients with this, and we find that the inside of the bladder starts to bleed due to this inflammation.

When the wall of the bladder becomes inflamed, the lining becomes very fragile. We keep bacteria out primarily through the skin, so within the bladder, the lining keeps bacteria away. However, when inflammation occurs, that protective skin layer breaks down. As the lining of the bladder has become disrupted, bacteria start to live inside the bladder.

Interestingly, the bacteria that we are finding now inside patients’ bladder is very different to what we found before the outbreak of COVID-19. So, it is a completely different organism because the environment of the bladder has become very different.

Is the course of treatment the same as it would be without the patient also suffering from long COVID?

Treatment of a patient with COVID-19 is normally very acute, with the main aim being to reduce one’s temperature. Usually, patients would be assessed to see if they had a chest infection, and whether this chest infection was caused by bacteria or a left-over of the COVID-19 infection. Patients’ bowel will also be examined.

The long COVID symptoms, however, are present for 12 weeks after the initial infection, so this is something that has an entirely different aspect to it, when compared with acute, “standard” if you like, treatment.

We are not treating a virus or the effects of the virus acutely, but we are trying to calm the immune system that has become angry.

What is your advice for people suffering from long COVID?

The majority of patients that I have seen have had bladder problems, and that I happened to notice that they had other symptoms in the body. We have found that these symptoms really improve with treatment.

One of the crucial things is that vigorous exercise, or trying to beat long COVID does not work, and people end up a lot worse. Try to avoid intense levels of exercise when you are recovering. It is important to exclude other infections as well, such as chest infections and bowel infections. So, it is very important to get these infections under control as quickly as possible because if there is an infection in the body, the immune system is not going to stop, as its job is to protect us at all costs.

What COVID-19 variants are going around in November 2022?

Authors: Nebraska Medicine November 1, 2022

There are currently more than 37,000 cases reported in the United States per day, with test positivity of 8.6%. When test positivity is above 5%, transmission is considered uncontrolled. There are more than 340 deaths per day, and hospitalizations have increased 8% over the last two weeks. 

What COVID-19 variant are we on?

Currently, the dominant variant nationwide is BA.5. “The original omicron variant is gone now,” says Dr. Rupp. “Currently subvariants of omicron are circulating, including BA.5, BA.4.6, BQ.1, BF.7 and BQ.1.1.” 
 

United States COVID-19 graphs through October 29, 2022.
Currently, BA.5 (dark green) is the dominant COVID-19 variant nationwide, followed by BA.4.6. Source: CDC Variant Proportions on November 1, 2022.

BA.5 variant dominating in Nebraska

BA.5 is also the dominant variant in Nebraska, making up 88% of cases. BA.4.6 is the next highest variant, with 6% of Nebraska cases.

Chart of COVID-19 variant data specific to Nebraska.
New COVID-19 variants displace older ones. In the last two weeks, Nebraska has seen an increase in omicron subvariants BA.5 (brown). Source: DHHS Nebraska on November 1, 2022. 

Which COVID-19 variant do I have? And do COVID-19 tests tell you the variant?

When you receive a COVID-19 test, you won’t find out which variant caused your infection. That’s because COVID-19 tests only detect the presence of the virus – they don’t determine the variant.

Genomic sequencing looks at the genetic code of the virus to determine which variant caused the infection.

Nebraska DHHS sequences test samples after a positive test is identified and reports the total percentage of each variant every two weeks. See the latest genomic surveillance report for Nebraska. Sequencing results are used by public health experts to understand variant trends in the community.

Will COVID-19 variants affect the vaccine?

The best way to prevent new variants is to slow the spread of the virus. The great news is that these proven public health strategies continue to work against new variants as well.

  • Get vaccinated
  • Choose outdoor activities over indoor activities whenever possible
  • Wash your hands often
  • Avoid close contact with others
  • Wear a mask in public places
  • Stay home if you’re sick or have symptoms of COVID-19

“We have a lot of disease out there. People should continue to be careful,” Dr. Rupp says. “Get your booster, try to avoid high-risk settings. If you can’t, then I think you should wear a mask.”

BA.4/BA.5 boosters, Novavax and vaccines for kids under 5

Everyone 5 years and up should get an updated COVID-19 booster, if eligible. These updated bivalent boosters offer protection against the latest omicron variants of BA.4 and BA.5, plus the original COVID-19 strain.

COVID-19 vaccines are now available for kids under 5. Now everyone ages 6 months and older can be vaccinated against COVID-19.

The Food and Drug Administration approved the Novavax vaccine July 19. As it uses a more traditional approach to vaccination and vaccine production than the mRNA vaccines already available, it may encourage some people who have not yet been vaccinated to accept vaccine. 

Novavax vaccines are available at the following Nebraska Medicine pharmacies:

As a community and nation, vaccination and booster dose rates need to increase. Evidence shows those vaccinated and boosted continue to be protected against severe disease, hospitalization, and death – even with the latest variants. Unfortunately, the United States is behind compared to other developed countries with only about 34% of those who are eligible to have received a booster actually getting the shot.

Facial Nerve Paralysis and COVID‐19: A Systematic Review

Authors: Amirpouyan Namavarian, MD, 1 Anas Eid, BMSc, 2 Hedyeh Ziai, MD, 1 Emily YiQin Cheng, BSc, 3 and Danny Enepekides, MD, MSc, FRCSC Laryngoscope. 2022 Aug 8 : 10.1002/lary.30333. doi: 10.1002/lary.30333

Abstract

Objective

Several cases of facial nerve paralysis (FNP) post‐COVID‐19 infection have been reported with varying presentations and management. This study aims to identify FNP clinical characteristics and recovery outcomes among patients acutely infected with COVID‐19. We hypothesize that FNP is a potentially unique sequalae associated with COVID‐19 infections.

Methods

A systematic review of PubMed‐Medline, OVID Embase, and Web of Science databases from inception to November 2021 was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines.

Results

This search identified 630 studies with 53 meeting inclusion criteria. This resulted in 72 patients, of which 30 (42%) were diagnosed with Guillain‐Barré Syndrome (GBS). Non‐GBS patients were on average younger (36 vs. 53 years) and more likely to present with unilateral FNP (88%) compared to GBS patients who presented predominantly with bilateral FNP (74%). Among non‐GBS patients, majority (70%) of FNP presented a median of 8 [IQR 10] days after the onset of initial COVID‐19 symptom(s). Treatment for non‐GBS patients consisted of steroids (60%), antivirals (29%), antibiotics (21%), and no treatment (21%). Complete FNP recovery in non‐GBS patients was achieved in 67% patients within a median of 11 [IQR 24] days.

Conclusion

FNP is a possible presentation post COVID‐19 infections, associated with both GBS and non‐GBS patients. Although no causation can be assumed, the clinical course of isolated FNP associated with COVID‐19 raises the possibility of a unique presentation differing from Bell’s palsy, seen with higher proportion of patients developing bilateral FNP and a shorter duration to complete recovery. Laryngoscope, 2022

Keywords: Bell’s palsy, COVID‐19, facial nerve, paralysis

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Abstract

Several cases of facial nerve paralysis (FNP) post‐COVID‐19 infection have been reported. This study aims to identify FNP clinical characteristics and recovery outcomes among patients acutely infected with COVID‐19. A systematic review of databases was performed resulting in 53 included studies and a total of 72 patients, of which 30 (42%) were diagnosed with Guillain‐Barré Syndrome (GBS). Among non‐GBS patients, 70% of FNP presented a median of 8 days after the onset of initial COVID‐19 symptom(s). Complete FNP recovery in non‐GBS patients was achieved in 67% patients within a median of 11 days. Although no causation can be assumed, the clinical course of isolated FNP associated with COVID‐19 raises the possibility of a unique presentation differing from Bell’s palsy, seen with higher proportion of patients developing bilateral FNP and a shorter duration to complete recovery.

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INTRODUCTION

Facial nerve paralysis/palsy (FNP) is a debilitating condition with significant morbidity associated with functional and psychological implications. 1 Although the etiology of FNP is broad, viral‐associated Bell’s palsy is thought to be the most prevalent contributor. 2 Herpes simplex virus (HSV) and Varicella zoster virus (VZV) are known contributors in the development of Bell’s Palsy in the pediatric and adult population. 3 Since the onset of the COVID‐19 pandemic, FNP incidence has increased and there has been a suggested association with COVID‐19 infections. 5 8

Many neurological symptoms have been reported in patients infected with COVID‐19 including anosmia, ageusia, myalgia, paraplegias, and facial palsy among others. 9 10 FNP has been described by numerous studies as an outcome of COVID‐19, either as an isolated symptom in patients who have otherwise been asymptomatic or in combination with other COVID‐19 symptoms. 6 11 Guillain‐Barré Syndrome (GBS), an autoimmune polyneuropathy, is linked to viral infections including Epstein–Barr virus (EBV), VZV, human immunodeficiency virus, and influenza among others. 12 GBS has also been described by numerous case reports as a sequelae of COVID‐19 infections, with many reported cases of FNP. 13 The mechanism of GBS is believed to involve an aberrant immune response resulting in nerve trauma secondary to inappropriate complement activation and inflammatory mediators. 14

The current literature highlights facial paralysis in COVID‐19 infected patients including both adult and pediatric cohorts. Although many case reports have described the presence of acute facial paralysis in COVID‐19 patients, to date, there is no comprehensive systematic review on these patients. The objective of this study is to identify FNP clinical characteristics and recovery outcomes among patients acutely infected with COVID‐19 (confirmed by a positive reverse transcription polymerase chain reaction [RT‐PCR]). We hypothesize that FNP is a potentially unique sequalae associated with COVID‐19 infections. In this systematic review, we summarize the current literature on the presentations of facial nerve paralysis in COVID‐19 patients and describe the management of these patients with the aim of providing guidance for future practitioners on these patients’ clinical diagnosis and management.

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METHODS

Search Strategy

This systematic review was completed using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines (Fig. 1). The search strategy was conducted using Ovid Embase, PubMed‐Medline, CINAHL and Web of Science databases from inception to November 2021. The database search was done by two reviewers (a.e./a.n.). Keywords and medical subject headings (MeSH) included facial, facial nerve, peripheral facial nerve, paralysis, paresis, palsy, droop, impair*, Bell’s palsy, weakness, disease, movement, COVID‐19, coronavirus, covid, and SARS‐CoV‐2. The exact search details used for all databases are found in Table S1.

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Fig. 1

PRISMA flow diagram. aTwo studies were included after a screen of the citations from the papers during the eligibility phase. RT‐PCR = reverse transcription polymerase chain reaction. [Color figure can be viewed in the online issue, which is available at www.laryngoscope.com.]

Inclusion and Exclusion Criteria

Inclusion criteria consisted of studies reporting FNP in adult and/or pediatric patients actively infected with COVID‐19. This was defined as a positive COVID‐19 RT‐PCR result. There was no comparator and the outcomes recorded included study design, patient demographic, and FNP clinical characteristics and recovery outcome. Published original studies including case reports, randomized controlled trials, prospective, or retrospective observational studies, cross‐sectional and case–control trials since journal inception were included. Patients with non‐active COVID‐19 infections (i.e., negative RT‐PCR results) despite positive serology (positive immunoglobulin G) were excluded. Furthermore, papers published in a non‐English language or non‐peer reviewed publications (abstracts, conference posters, reviews, letters to editors, and editorials) were also excluded.

Data Extraction and Analysis

The search titles and abstracts were independently screened by two reviewers (a.e./a.n.) based on the inclusion and exclusion criteria. Complete manuscripts were retrieved and independently reviewed by the same two reviewers. If there were any disagreements in article selection between the two reviewers, these were resolved by consensus. If a disagreement persisted, a third reviewer was consulted (h.z.). All titles, abstracts, and full texts screening were completed using Covidence (version 1501). Cross‐checking of the included articles and relevant reviews, as well as a manual web search was conducted for unidentified articles. Extracted data included study design, study population demographics, and clinical characteristics. Information regarding FNP onset, laterality, House‐Brackmann (HB) score, associated symptoms, investigations, treatments, and outcomes was extracted. Patients in studies that did not report HB score were assigned a score by the reviewers based on the described clinical presentation and HB scale by the reviewers when possible. 15 Similarly, if there was any disagreement between the two reviewers, a third reviewer was consulted.

Risk of Bias Assessment

The Joanna Briggs Institute critical appraisal checklist for case reports and case series assessment tools were used to appraise the quality of the studies. This was independently assessed by two authors (a.e. and e.c.). Discrepancies were resolved by consensus or by involving a third author (a.n.). The quality of the studies was quantified according to the assessment tools and a final quality rating of “Good,” “Fair,” or “Poor” was given (Table S2A and B). For case reports, “Good” was defined as at least 6 out of 8 criteria met, “Fair” as 4 or 5 criteria met, and “Poor” as 3 or less criteria met. For case series, “Good” was defined as at least 7 out of 10 criteria met, “Fair” as 5 or 6 criteria met, and “Poor” as 4 or less criteria met.

Statistical Analysis

Descriptive statistics were computed for all variables. Categorical variables were reported as unweighted frequencies and percentages. Continuous variables were reported as medians and interquartile range (IQR). Subgroup analysis was performed based on GBS status. IBM SPSS Statistics for Windows, Version 27.0 was used for all statistical analyses.

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RESULTS

Study Selection

Our search identified 1064 studies. After duplicates were removed, a total of 630 studies were reviewed for initial screening. Fifty‐two studies met our inclusion, and two studies were found during our screen of citations listed in our included papers. A total of 54 studies were included (Fig. 1), resulting in 73 patients. 5 10 11 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 The characteristics of each study can be found in Table S3.

Clinical Features: Non‐GBS Versus GBS Patients

The clinical presentations are summarized in Table I. Forty‐two percent of patients presented with FNP in the context of GBS. Patients without GBS were younger than those with GBS (36 vs. 54 years, respectively). Additionally, more non‐GBS patients presented with unilateral FNP compared to those with GBS (88% vs. 26%, respectively). Furthermore, non‐GBS patients had a shorter delay to FNP onset (median [IQR]; 8 [10] days) from the onset of initial COVID‐19 symptoms compared to GBS patients (16 [11] days).

TABLE I

Overall Study Demographics and FNP Clinical Presentations.

Non‐GBS (n = 42)GBS (n = 30)
Patients (%)5842
Age (years), median [IQR]36 [22]54 [23]
Male, n (%)19 (49)21 (70)
Onset of FNP relative to COVID‐19 symptoms, n (%)
Only FNP4 (11)0
Before or concurrent7 (19)2 (6.8)
After26 (70)27 (93.1)
Days from initial symptoms to onset of FNP, median [IQR]8 [10]16 [11]
Unilateral FNP, n (%)37 (88)7 (25.9)
Degree of FNP, median [IQR]3 [2]4.5 [3]
Complete recovery of FNP achieved, n (%)20 (67)4 (13.3)
Days to complete recovery of FNP, median11 [24]30

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FNP = facial nerve paralysis; GBS = Guillain‐Barré Syndrome; IQR = interquartile range.

Thirty‐two studies reported the severity of the FNP using the House‐Brackmann scale, the median grade was 3 [IQR 2] and 4.5 [3] for non‐GBS and GBS patients, respectively.

Of the COVID‐19 symptoms, the most reported were fever (36% and 60% in non‐GBS and GBS patients, respectively) and cough (32% and 63% in non‐GBS and GBS patients, respectively). When considering neurological symptoms in patients with COVID‐19 other than FNP, impairments in taste function (e.g., ageusia, hypogeusia or dysgeusia) were most reported (10% in non‐GBS vs. 37% in GBS) followed by impairments in olfaction (8% and 23% in non‐GBS and GBS patients, respectively). The detailed distribution of symptoms associated with COVID‐19 is found in Table II.

TABLE II

Patient Symptoms.

SymptomNon‐GBS (n = 42), n (%)GBS (n = 30), n (%)
Non‐neurologic
Fever10 (36)18 (60)
Cough9 (32)19 (63.3)
Myalgia8 (29)5 (16.7)
Dyspnea5 (18)7 (23.3)
Fatigue3 (11)5 (16.7)
Neurologic
Anosmia or hyposmia3 (8)7 (23.3)
Ageusia, hypogeusia, dysgeusia4 (10)11 (36.7)
Dysarthria04 (13.3)
Dysphagia04 (13.3)
Odynophagia1 (3)1 (3.3)
Diplopia1 (3)3 (10)

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GBS = Guillain‐Barré Syndrome.

When considering the distribution of non‐neurological COVID‐19 symptoms based on patient GBS status, more GBS patients presented with a cough compared to non‐GBS patients (63% vs. 32%, respectively) (Table II). More GBS presented with taste dysfunction (37% vs. 10%), dysarthria (13% vs. 0%), and dysphagia (13% vs. 0%) compared with non‐GBS patients.

Imaging

The distribution of utilized imaging investigations is shown in Table S3. Magnetic resonance imaging was performed in 36 patients, all of which reported no structural pathology contributing to their FNP (i.e., retro cochlear or middle ear pathology).

Treatment

A summary of the management is shown in Table III. The non‐GBS patients were most frequently treated with steroids (n = 25, 60%), followed by antivirals (n = 12, 29%), antibiotics (n = 9, 21%), symptom management/no treatment (n = 9, 21%), intravenous immunoglobulins (IVIG) (n = 4, 10%), hydroxychloroquine (n = 4, 10%), and physiotherapy (n = 2, 5%). On the other hand, patients with GBS were most treated with IVIG (n = 24, 80%), followed by hydroxychloroquine (n = 12, 43%), plasmapheresis (n = 8, 27%), steroids (n = 7, 23%), antivirals (n = 6, 21%), antibiotics (n = 6, 21%), and physiotherapy (n = 1, 3%).

TABLE III

Patient Management.

TreatmentNon‐GBS (%)GBS (%)
Steroids25 (60)7 (23.3)
Antivirals12 (29)6 (21.4)
Antibiotics9 (21)6 (21.4)
Hydroxychloroquine4 (10)12 (42.9)
IVIG4 (10)24 (80)
Plasmapheresis08 (26.7)
Physiotherapy2 (5)1 (3.3)
No treatment9 (21)0

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GBS = Guillain‐Barré Syndrome; IVIG = intravenous immunoglobulins.

Recovery Outcomes: Non‐GBS Versus GBS

More patients presenting without GBS had complete recovery of their FNP symptoms compared to those with GBS (67% vs. 13% respectively; Table I). Among those with complete recovery in the non‐GBS group, the majority (80%) did not have any additional neurological symptoms, whereas a minority (20%) had further cranial nerve involvement. Fifty‐three percent (n = 8) of those 15 patients treated with steroids in the non‐GBS group completely recovered within 60 days. In contrast, only 15% (n = 2/13) of the GBS patients treated with IVIG achieved complete FNP recovery within 44 days. There was insufficient data on steroid therapy among GBS patients to compare outcomes to non‐GBS patients.

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DISCUSSION

This systematic review summarizes FNP in the context of COVID‐19 infections highlighting patients with systemic autoimmune pathology of GBS and isolated FNP (non‐GBS). Most patients had moderate FNP as graded on the HB scale. Of the reported non‐neurological COVID‐19 symptoms, the most common were fever and cough. Patients with and without GBS during COVID‐19 infections presented and progressed with FNP differently, with GBS patients typically presenting with a delayed onset, more severe FNP, and worse facial nerve outcomes. Additionally, the clinical course of isolated FNP associated with COVID‐19 appears to differ from typical Bell’s palsy. Non‐GBS FNP patients had a shorter duration to complete recovery and a higher proportion of bilateral FNP compared to Bell’s palsy patients. This suggests that we may be observing an etiology different than Bell’s palsy patients with differing presentation and prognosis.

Patients diagnosed with GBS were on average older than non‐GBS patients and the duration from the onset of COVID‐19 symptoms to the manifestation of FNP differed considerably between the GBS and non‐GBS diagnosed subgroups. The most common treatments for non‐GBS patients consisted of steroids, antivirals, and antibiotics. Complete recovery of FNP in non‐GBS patients was achieved in over two thirds of patients within an average of under 3 weeks. In contrast, only 17% of GBS patients achieved complete recovery of FNP within an average of over a month.

Clinical Presentation

The initial COVID‐19 symptoms including cough, fever, and dyspnea can be challenging to interpret as they are similar to common upper respiratory tract infections. With the advent of COVID‐19, clinical suspicion of these symptoms has become increasingly recognized and should also be considered when taking a history from a patient presenting with acute FNP. In the context of known viral etiologies related to FNP, COVID‐19 infected patients presented differently. For example, when evaluating the non‐GBS patient category, most patients with FNP after COVID‐19 infection (70%) presented on average 9 days (1–20 days) after the onset of initial COVID‐19 symptom(s). In comparison, FNP secondary to Ramsay Hunt syndrome typically presents either before or concurrently with the typical manifestations including VZV blisters. 64 65

In terms of laterality, bilateral FNP is an extremely rare clinical manifestation of Bell’s palsy, accounting for only up to 2% of these patients. 66 67 68 69 In comparison, a larger proportion (12%) of the isolated FNP patients in this review presented with bilateral FNP. This may be explained by the potentially greater inflammatory impact of the COVID‐19 virus on the facial nerve that has been previously hypothesized. 6 In our study, approximately 75% of the GBS patients presented with bilateral FNP which was higher than non‐GBS patients. Unlike Bell’s palsy, GBS has systemic involvement, more severe symptoms, and highly variable clinical course and outcome. 70

Lastly, a small minority (11%) of the non‐GBS patients presented with FNP as either their presenting or sole symptom of COVID‐19 during an active infection. These findings highlight the importance of considering COVID‐19 infection in the differential diagnosis when evaluating patients with isolated FNP symptoms who may otherwise be asymptomatic. An RT‐PCR for COVID‐19 may be considered in an infectious work‐up of patients presenting with isolated FNP.

Treatments and Outcomes

The most common treatment for non‐GBS patients consisted of steroids, antivirals, and/or antibiotics. Twenty percent of patients had no treatment. According to the American Academy of Neurology (AAN) and the American Academy of Otolaryngology‐Head and Neck Surgery Foundation (AAO‐HNSF), the treatment of Bell’s palsy primarily focuses on the use of corticosteroids and advises against the routine use of antiviral therapy. 71 72 73 However, previous studies have shown that treatment of FNP from Bell’s palsy and RHS with acyclovir and prednisone leads to better outcomes. 74 75 Half of those treated with steroids and half of patients treated with antiviral therapy had complete recovery within 60 days. Among our non‐GBS patients, there were no differences in outcomes between prednisone monotherapy and the combination therapy with antivirals.

Our findings suggest that patients with GBS who develop FNP were more likely to develop severe presentations and were more prone to worse clinical outcomes. Patients presenting with FNP in the context of GBS were most treated with IVIG, followed by hydroxychloroquine, plasmapheresis, and/or steroids. The first line treatments for GBS are plasma exchange or IVIG therapy which should be initiated within 7 and 14 days of symptom onset, respectively, to hasten recovery. 76 In contrast, corticosteroids are not recommended for the treatment of GBS, as several clinical trials have shown no benefit in recovery outcomes compared to placebo. 77 This could explain why steroids were much less commonly used in our GBS patients compared to plasmapheresis and IVIG. Importantly, patients presenting with GBS and FNP were over three times less likely to have complete recovery of FNP compared to non‐GBS patients. This can be explained by the systemic involvement of GBS with more severe symptoms, and highly variable clinical course and outcome. 70

When comparing patients with Bell’s palsy, FNP associated with COVID‐19 infection appeared to have a shorter time to complete recovery. Complete recovery of FNP in non‐GBS patients was achieved in over two thirds of patients within almost 20 days with and without treatments. Previous studies on the natural history of Bell’s palsy have suggested that approximately 85% of patients begin to experience some recovery of their FNP within the first 3 weeks. 71 However, complete recovery of Bell’s palsy with steroid treatment is typically seen in 3–9 months and our study was limited in terms of follow up duration. 78 In our non‐GBS cohort, complete recovery was achieved in the majority (62%) within the first 2 months.

Although our study did not identify any significant predictors of FNP outcomes related to treatment for COVID‐19 patients, this is likely due to the limited sample size, and is an area for future research.

Etiology

Infectious etiology of FNP has a broad differential. Presumed culprits include HSV, VZV, EBV, and Borrelia burgdorferi. With the advent of COVID‐19, our results suggest that the etiology of FNP in non‐GBS COVID‐19 patients is potentially novel.

COVID‐19 has been hypothesized to cause neurologic damage by two distinct mechanisms: (1) dissemination to the central nervous system by hematogenous spread or trans‐neuronally via cranial nerves causing direct neuronal damage due to viral neurotropism and (2) neuronal damage secondary to an abnormal immune‐mediated response. 6 79 The first is thought to be responsible for cranial nerve manifestations (e.g., hypogeusia, hyposmia, headache, and vertigo), whereas the latter mechanism is believed to result in severe complications and contribute to the development of dysimmune neuropathies like GBS. 13 80

Our findings indicate that among the non‐GBS patients, a suggestion can be made of an association between COVID‐19 and a clinical manifestation of FNP, although no causation can be assumed. Although the acute onset and age distribution of the non‐GBS patients present similarly to Bell’s palsy, the differences in clinical presentations and outcomes should be considered. The non‐GBS subgroup had a relatively shorter duration to complete recovery and a higher proportion of bilateral FNP compared to Bell’s palsy patients. 69 78

This study is not without limitations. Firstly, a full infectious work‐up to rule out other potential infectious causes of FNP was done in only 41% patients, although it was non‐contributory except for one patient who also had an active concurrent EBV infection. Secondly, there was variability in the length of follow‐up with the majority being 60 days or less and thus long‐term outcomes data are limited. Since the full recovery of Bell’s palsy typically occurs within a year, this limitation may be underestimating the recovery in our patients. Furthermore, we did not discuss treatment specific outcomes as we were unable to control for multiple patient specific variables and concurrent treatments. Another important limitation is that case reports and case series are more likely to report severe manifestations of COVID‐19. Therefore, the patients included in our study may not represent the complete spectrum of FNP associated COVID‐19, and instead could underestimate the true prevalence of mild, undifferentiated, or undiagnosed cases. Additionally, the onset of FNP was determined relative to patient awareness of related COVID‐19 symptom(s) which may have been non‐specific and may not have been accurately reported. Finally, since the completion of our literature search in November 2021, subsequent omicron and delta variants may not have been adequately represented in our results. Despite these limitations, this study is the first systematic review on patients with COVID‐19 and FNP and may help advance knowledge and guide management of these patients.

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CONCLUSION

Although COVID‐19 symptoms are predominantly respiratory, emerging evidence has highlighted various neurologic manifestations associated with COVID‐19 infections. Our study highlights and delineates the presentations of FNP in the context of COVID‐19 for systemic conditions such as GBS as well as an isolated FNP. Systemic and isolated cases of FNP during COVID‐19 infections present and progress differently. Additionally, the clinical course of isolated FNP associated with COVID‐19 appears to differ from typical Bell’s palsy presentation and prognosis. This suggests that patients with COVID‐19 may have an atypical presentation of Bell’s palsy with a more severe initial presentation and a relatively better prognosis with higher propensity for complete recovery. This review suggests COVID‐19 infection may be associated with the development of a unique clinical manifestation of FNP. There is some literature associating FNP with COVID‐19, although a causal association cannot be definitively assumed. Our study may help future practitioners in identifying FNP as a possible sequela of COVID‐19 infection that may aid in the management of these patients.

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Supporting information

Table S1. Database Search Algorithm.

Table S2A. Case Reports Risk of Bias Assessment.

Table S2B. Case Series Risk of Bias Assessment.

Table S3. Study Demographics

Click here for additional data file.(93K, docx)

REFERENCES

1. Movérare T, Lohmander A, Hultcrantz M, Sjögreen L. Peripheral facial palsy: speech, communication and oral motor function. Eur Ann Otorhinolaryngol Head Neck Dis. 2017;134(1):27‐31. [PubMed] [Google Scholar]

2. Lorch M, Teach SJ. Facial nerve palsy: etiology and approach to diagnosis and treatment. Pediatr Emerg Care. 2010;26(10):763‐769. [PubMed] [Google Scholar]

3. Karalok ZS, Taskin BD, Ozturk Z, Gurkas E, Koc TB, Guven A. Childhood peripheral facial palsy. Childs Nerv Syst. 2018;34(5):911‐917. 10.1007/s00381-018-3742-9. [PubMed] [CrossRef] [Google Scholar]

4. Jeon Y, Lee H. Ramsay Hunt syndrome. J Dent Anesth Pain Med. 2018;18(6):333‐337. [PMC free article] [PubMed] [Google Scholar]

5. Goh Y, Beh DLL, Makmur A, Somani J, Chan ACY. Pearls & Oy‐sters: facial nerve palsy in COVID‐19 infection. Neurology. 2020;95(8):364‐367. [PubMed] [Google Scholar]

6. Lima MA, Silva MTT, Soares CN, et al. Peripheral facial nerve palsy associated with COVID‐19. J Neurovirol. 2020;26(6):941‐944. [PMC free article] [PubMed] [Google Scholar]

7. Figueiredo R, Falcão V, Pinto MJ, Ramalho C. Peripheral facial paralysis as presenting symptom of COVID‐19 in a pregnant woman. BMJ Case Rep. 2020;13(8):e237146. [PMC free article] [PubMed] [Google Scholar]

8. Brisca G, Garbarino F, Carta S, et al. Increased childhood peripheral facial palsy in the emergency department during COVID‐19 pandemic. Pediatr Emerg Care. 2020;36(10):E595‐E596. [PubMed] [Google Scholar]

9. Mackenzie N, Lopez‐Coronel E, Dau A, et al. Concomitant Guillain‐Barre syndrome with COVID‐19: a case report. BMC Neurol. 2021;21(1):135. [PMC free article] [PubMed] [Google Scholar]

10. Ottaviani D, Boso F, Tranquillini E, et al. Early Guillain‐Barré syndrome in coronavirus disease 2019 (COVID‐19): a case report from an Italian COVID‐hospital. Neurol Sci. 2020;41(6):1351‐1354. [PMC free article] [PubMed] [Google Scholar]

11. Bsales S, Olson B, Gaur S, et al. Bell’s palsy associated with SARS‐CoV‐2 infection in a 2‐year‐old child. J Pediatr Neurol. 2021;19(6):440‐442. [Google Scholar]

12. Jasti AK, Selmi C, Sarmiento‐Monroy JC, Vega DA, Anaya JM, Gershwin ME. Guillain‐Barré syndrome: causes, immunopathogenic mechanisms and treatment. Expert Rev Clin Immunol. 2016;12(11):1175‐1189. [PubMed] [Google Scholar]

13. Abu‐Rumeileh S, Abdelhak A, Foschi M, Tumani H, Otto M. Guillain–Barré syndrome spectrum associated with COVID‐19: an up‐to‐date systematic review of 73 cases. J Neurol. 2021;268(4):1133‐1170. [PMC free article] [PubMed] [Google Scholar]

14. Walling AD, Dickson G. Guillain‐Barre syndrome. Am Fam Physician. 2013;87(3):191‐197. [PubMed] [Google Scholar]

15. House JW, Brackmann DE. Facial nerve grading system. Otolaryngol Head Neck Surg. 1985;93(2):146‐147. [PubMed] [Google Scholar]

16. Cabrera Muras A, Carmona‐Abellán MM, Collía Fernández A, Uterga Valiente JM, Antón Méndez L, García‐Moncó JC. Bilateral facial nerve palsy associated with COVID‐19 and Epstein‐Barr virus co‐infection. Eur J Neurol. 2021;28(1):358‐360. [PMC free article] [PubMed] [Google Scholar]

17. Chan JL, Ebadi H, Sarna JR. Guillain‐Barré syndrome with facial diplegia related to SARS‐CoV‐2 infection. Can J Neurol Sci. 2020;47(6):1‐854. [PMC free article] [PubMed] [Google Scholar]

18. Chan M, Han SC, Kelly S, Tamimi M, Giglio B, Lewis A. A case series of Guillain‐Barré syndrome after COVID‐19 infection in New York. Neurol Clin Pract. 2021;11(4):e576‐e578. [PMC free article] [PubMed] [Google Scholar]

19. Chaumont H, San‐Galli A, Martino F, et al. Mixed central and peripheral nervous system disorders in severe SARS‐CoV‐2 infection. J Neurol. 2020;267(11):1‐3127. [PMC free article] [PubMed] [Google Scholar]

20. Corrêa DG, Hygino da Cruz LC, Lopes FCR, et al. Magnetic resonance imaging features of COVID‐19‐related cranial nerve lesions. J Neurovirol. 2021;27(1):1. [PMC free article] [PubMed] [Google Scholar]

21. Dahl EH, Mosevoll KA, Cramariuc D, Vedeler CA, Blomberg B. COVID‐19 myocarditis and postinfection Bell’s palsy. BMJ Case Rep. 2021;14(1):e240095. [PMC free article] [PubMed] [Google Scholar]

22. de Freitas Ribeiro BN, Marchiori E. Facial palsy as a neurological complication of SARS‐CoV‐2. Arq Neuropsiquiatr. 2020;78(10):667. [PubMed] [Google Scholar]

23. Derollez C, Alberto T, Leroi I, Mackowiak MA, Chen Y. Facial nerve palsy: an atypical clinical manifestation of COVID‐19 infection in a family cluster. Eur J Neurol. 2020;27(12):2670‐2672. [PMC free article] [PubMed] [Google Scholar]

24. Doo FX, Kassim G, Lefton DR, Patterson S, Pham H, Belani P. Rare presentations of COVID‐19: PRES‐like leukoencephalopathy and carotid thrombosis. Clin Imaging. 2021;69:94‐101. [PMC free article] [PubMed] [Google Scholar]

25. Gogia B, Gil Guevara A, Rai PK, Fang X. A case of COVID‐19 with multiple cranial neuropathies. Int J Neurosci. 2020;1‐3. 10.1080/00207454.2020.1869001. [PubMed] [CrossRef] [Google Scholar]

26. González‐Castro A, Rodríguez ER, Arnaiz F, Pargada DF. Parálisis facial periférica en pacientes con SARS‐CoV‐2 en decúbito prono. Rev Neurol. 2021;72(8):296‐297. [PubMed] [Google Scholar]

27. Guilmot A, Maldonado Slootjes S, Sellimi A, et al. Immune‐mediated neurological syndromes in SARS‐CoV‐2‐infected patients. J Neurol. 2021;268(3):751‐757. [PMC free article] [PubMed] [Google Scholar]

28. Homma Y, Watanabe M, Inoue K, Moritaka T. Coronavirus disease‐19 pneumonia with facial nerve palsy and olfactory disturbance. Intern Med. 2020;59(14):1773‐1775. [PMC free article] [PubMed] [Google Scholar]

29. Hutchins KL, Jansen JH, Comer AD, et al. COVID‐19‐associated bifacial weakness with paresthesia subtype of Guillain‐Barré syndrome. AJNR Am J Neuroradiol. 2020;41(9):1707‐1711. [PMC free article] [PubMed] [Google Scholar]

30. Juliao Caamaño DS, Alonso Beato R. Facial diplegia, a possible atypical variant of Guillain‐Barré syndrome as a rare neurological complication of SARS‐CoV‐2. J Clin Neurosci. 2020;77:230‐232. [PMC free article] [PubMed] [Google Scholar]

31. Kaplan AC. Noteworthy neurological manifestations associated with COVID‐19 infection. Cureus. 2021;13(4):e14391. [PMC free article] [PubMed] [Google Scholar]

32. Khaja M, Roa Gomez GP, Santana Y, et al. A 44‐year‐old Hispanic man with loss of taste and bilateral facial weakness diagnosed with Guillain‐Barré syndrome and Bell’s palsy associated with SARS‐CoV‐2 infection treated with intravenous immunoglobulin. Am J Case Rep. 2020;21:e927956‐e927951. [PMC free article] [PubMed] [Google Scholar]

33. Kilinc D, van de Pasch S, Doets AY, Jacobs BC, van Vliet J, Garssen MPJ. Guillain–Barré syndrome after SARS‐CoV‐2 infection. Eur J Neurol. 2020;27(9):1757‐1758. [PMC free article] [PubMed] [Google Scholar]

34. Kumar V, Narayanan P, Shetty S, Mohammed AP. Lower motor neuron facial palsy in a postnatal mother with COVID‐19. BMJ Case Rep. 2021;14(3):e240267. [PMC free article] [PubMed] [Google Scholar]

35. Lascano AM, Epiney JB, Coen M, et al. SARS‐CoV‐2 and Guillain‐Barré syndrome: AIDP variant with a favourable outcome. Eur J Neurol. 2020;27(9):1751‐1753. [PMC free article] [PubMed] [Google Scholar]

36. Manganotti P, Bellavita G, D’Acunto L, et al. Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain‐Barré syndrome and polyneuritis cranialis in COVID‐19 patients: a case series. J Med Virol. 2021;93(2):766‐774. [PMC free article] [PubMed] [Google Scholar]

37. McDonnell EP, Altomare NJ, Parekh YH, et al. COVID‐19 as a trigger of recurrent Guillain–Barré syndrome. Pathogens. 2020;9(11):1‐9. [PMC free article] [PubMed] [Google Scholar]

38. Mehta S, Mackinnon D, Gupta S. Severe acute respiratory syndrome coronavirus 2 as an atypical cause of Bell’s palsy in a patient experiencing homelessness. CJEM. 2020;22(5):1‐610. [PMC free article] [PubMed] [Google Scholar]

39. Nanda S, Handa R, Prasad A, et al. Covid‐19 associated Guillain‐Barre syndrome: contrasting tale of four patients from a tertiary care centre in India. Am J Emerg Med. 2021;39:125‐128. [PMC free article] [PubMed] [Google Scholar]

40. Neo WL, Ng JCF, Iyer NG. The great pretender—Bell’s palsy secondary to SARS‐CoV‐2? Clin Case Rep. 2021;9(3):1175‐1177. [PMC free article] [PubMed] [Google Scholar]

41. Ochoa‐Fernández EG, Víllora‐Morcillo N, Taboas‐Pereira A. Parálisis facial periférica en un paciente pediátrico sin factores de riesgo en el contexto de infección por SARS‐CoV‐2. Rev Neurol. 2021;72(5):177‐178. [PubMed] [Google Scholar]

42. Oke IO, Oladunjoye OO, Oladunjoye AO, Paudel A, Zimmerman R. Bell’s palsy as a late neurologic manifestation of COVID‐19 infection. Cureus. 2021;13(3):e13881. [PMC free article] [PubMed] [Google Scholar]

43. Paybast S, Gorji R, Mavandadi S. Guillain‐Barré syndrome as a neurological complication of novel COVID‐19 infection: a case report and review of the literature. Neurologist. 2020;25(4):101‐103. [PMC free article] [PubMed] [Google Scholar]

44. Pelea T, Reuter U, Schmidt C, Laubinger R, Siegmund R, Walther BW. SARS‐CoV‐2 associated Guillain–Barré syndrome. J Neurol. 2021;268(4):1191‐1194. [PMC free article] [PubMed] [Google Scholar]

45. Pfefferkorn T, Dabitz R, von Wernitz‐Keibel T, Aufenanger J, Nowak‐Machen M, Janssen H. Acute polyradiculoneuritis with locked‐in syndrome in a patient with Covid‐19. J Neurol. 2020;267(7):1‐1884. [PMC free article] [PubMed] [Google Scholar]

46. Pinna P, Grewal P, Hall JP, et al. Neurological manifestations and COVID‐19: experiences from a tertiary care center at the frontline. J Neurol Sci. 2020;415:116969. [PMC free article] [PubMed] [Google Scholar]

47. Rana S, Lima AA, Chandra R, et al. Novel coronavirus (COVID‐19)‐associated Guillain–Barré syndrome: case report. J Clin Neuromuscul Dis. 2020;21(4):240‐242. [PMC free article] [PubMed] [Google Scholar]

48. Reyes‐Bueno JA, García‐Trujillo L, Urbaneja P, et al. Miller‐Fisher syndrome after SARS‐CoV‐2 infection. Eur J Neurol. 2020;27(9):1759‐1761. [PMC free article] [PubMed] [Google Scholar]

49. Saberi H, Tanha RR, Derakhshanrad N, Soltaninejad MJ. Acute presentation of third ventricular cavernous malformation following COVID‐19 infection in a pregnant woman: a case report. Neurochirurgie. 2021;68(2):228‐231. [PMC free article] [PubMed] [Google Scholar]

50. Sancho‐Saldaña A, Lambea‐Gil Á, Capablo Liesa JL, et al. Guillain–Barré syndrome associated with leptomeningeal enhancement following SARS‐CoV‐2 infection. Clin Med. 2020;20(4):e93‐e94. [PMC free article] [PubMed] [Google Scholar]

51. Sedaghat Z, Karimi N. Guillain Barre syndrome associated with COVID‐19 infection: a case report. J Clin Neurosci. 2020;76:233‐235. [PMC free article] [PubMed] [Google Scholar]

52. Tard C, Maurage CA, de Paula AM, et al. Anti‐pan‐neurofascin IgM in COVID‐19‐related Guillain‐Barré syndrome: evidence for a nodo‐paranodopathy. Neurophysiol Clin. 2020;50(5):397‐399. [PMC free article] [PubMed] [Google Scholar]

53. Taşlıdere B, Mehmetaj L, Özcan AB, Gülen B, Taşlıdere N. Melkersson‐Rosenthal syndrome induced by COVID‐19. Am J Emerg Med. 2021;41:262.e5‐262.e7. [PMC free article] [PubMed] [Google Scholar]

54. Tekin AB, Zanapalioglu U, Gulmez S, Akarsu I, Yassa M, Tug N. Guillain Barre syndrome following delivery in a pregnant woman infected with SARS‐CoV‐2. J Clin Neurosci. 2021;86:190‐192. [PMC free article] [PubMed] [Google Scholar]

55. Theophanous C, Santoro JD, Itani R. Bell’s palsy in a pediatric patient with hyper IgM syndrome and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Brain Dev. 2021;43(2):357‐359. [PMC free article] [PubMed] [Google Scholar]

56. Tiet MY, Alshaikh N. Guillain‐Barré syndrome associated with COVID‐19 infection: a case from the UK. BMJ Case Rep. 2020;13(7):e236536. [PMC free article] [PubMed] [Google Scholar]

57. Toscano G, Palmerini F, Ravaglia S, et al. Guillain‐Barré syndrome associated with SARS‐CoV‐2. N Engl J Med. 2020;382(26):2574‐2576. [PMC free article] [PubMed] [Google Scholar]

58. Wong PF, Craik S, Newman P, et al. Lessons of the month 1: a case of rhombencephalitis as a rare complication of acute COVID‐19 infection. Clin Med (Northfield Il). 2020;20(3):293‐294. [PMC free article] [PubMed] [Google Scholar]

59. Zain S, Petropoulou K, Mirchia K, Hussien A, Mirchia K. COVID‐19 as a rare cause of facial nerve neuritis in a pediatric patient. Radiol Case Rep. 2021;16(6):1400‐1404. [PMC free article] [PubMed] [Google Scholar]

60. Abolmaali M, Heidari M, Zeinali M, et al. Guillain–Barré syndrome as a parainfectious manifestation of SARS‐CoV‐2 infection: a case series. J Clin Neurosci. 2021;83:119‐122. [PMC free article] [PubMed] [Google Scholar]

61. Almutairi A, Bin Abdulqader S, Alhameed M, Alit S, Alosaimi B. Guillain‐Barré syndrome following COVID‐19: a case report. J Res Med Dent Sci. 2021;9(3):7‐10. [Google Scholar]

62. Bastola A, Sah R, Nepal G, et al. Bell’s palsy as a possible neurological complication of COVID‐19: a case report. Clin Case Rep. 2021;9(2):747‐750. [PMC free article] [PubMed] [Google Scholar]

63. Bigaut K, Mallaret M, Baloglu S, et al. Guillain‐Barré syndrome related to SARS‐CoV‐2 infection. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):785. [PMC free article] [PubMed] [Google Scholar]

64. Kanerva M, Jones S, Pitkaranta A. Ramsay Hunt syndrome: characteristics and patient self‐assessed long‐term facial palsy outcome. Eur Arch Otorhinolaryngol. 2020;277(4):1235‐1245. [PMC free article] [PubMed] [Google Scholar]

65. Aizawa H, Ohtani F, Futura Y, Sawa H, Fukuda S. Variable patterns of varicella‐zoster virus reactivation in Ramsay Hunt syndrome. J Med Virol. 2004;74(2):355‐360. [PubMed] [Google Scholar]

66. Adour KK, Byl FM, Hilsinger RL, Kahn ZM, Sheldon MI. The true nature of Bell’s palsy: analysis of 1,000 consecutive patients. Laryngoscope. 1978;88(5):787‐801. [PubMed] [Google Scholar]

67. Adour KK, Swanson PJ. Facial paralysis in 403 consecutive patients: emphasis on treatment response in patients with Bell’s palsy. Trans Am Acad Ophthalmol Otolaryngol. 1971;75(6):1284‐1301. [PubMed] [Google Scholar]

68. Leibowitz U. Bell’s palsy—two disease entities? Neurology. 1966;16(11):1105‐1109. [PubMed] [Google Scholar]

69. McGoveen FH. Bilateral Bell’s palsy. Laryngoscope. 1965;75(7):1070‐1080. [PubMed] [Google Scholar]

70. Van Den Berg B, Walgaard C, Drenthen J, Fokke C, Jacobs BC, Van Doorn PA. Guillain‐Barré syndrome: pathogenesis, diagnosis, treatment and prognosis. Nat Rev Neurol. 2014;10(8):469‐482. [PubMed] [Google Scholar]

71. Eviston TJ, Croxson GR, Kennedy PGE, Hadlock T, Krishnan AV. Bell’s palsy: aetiology, clinical features and multidisciplinary care. J Neurol Neurosurg Psychiatry. 2015;86(12):1356‐1361. [PubMed] [Google Scholar]

72. Baugh RF, Basura GJ, Ishii LE, et al. Clinical practice guideline: Bell’s palsy. Otolaryngol Head Neck Surg. 2013;149:S1‐S27. [PubMed] [Google Scholar]

73. Gronseth GS, Paduga R. Evidence‐based guideline update: steroids and antivirals for Bell palsy: report of the guideline development subcommittee of the American academy of neurology. Neurology. 2012;79(22):2209‐2213. [PubMed] [Google Scholar]

74. Tang IP, Lee SC, Shashinder S, Raman R. Outcome of patients presenting with idiopathic facial nerve paralysis (Bell’s palsy) in a tertiary centre ‐ a five year experience. Med J Malaysia. 2009;64(2):155‐158. [PubMed] [Google Scholar]

75. Da Costa Monsanto R, Bittencourt AG, Bobato Neto NJ, Beilke SCA, Lorenzetti FTM, Salomone R. Treatment and prognosis of facial palsy on Ramsay Hunt syndrome: results based on a review of the literature. Int Arch Otorhinolaryngol. 2016;20(4):394‐400. [PMC free article] [PubMed] [Google Scholar]

76. Raphaël JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain‐Barré syndrome. Cochrane Database Syst Rev. 2012;7:CD001798. [PubMed] [Google Scholar]

77. Hughes RA, Swan AV, van Koningsveld R, van Doorn PA. Corticosteroids for Guillain‐Barré syndrome. Cochrane Database Syst Rev. 2006;2:CD001446. [PubMed] [Google Scholar]

78. Sullivan FM, Swan IR, Donnan PT, et al. Early treatment with prednisolone or acyclovir in Bell’s palsy. Clin Otolaryngol. 2007;32(6):460. [PubMed] [Google Scholar]

79. Costello F, Dalakas MC. Cranial neuropathies and COVID‐19: neurotropism and autoimmunity. Neurology. 2020;95(5):195‐196. [PubMed] [Google Scholar]

80. Wang L, Shen Y, Li M, et al. Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS‐CoV‐2: a systematic review and meta‐analysis. J Neurol. 2020;267(10):2777‐2789. [PMC free article] [PubMed] [Google Scholar