Anyone who’s had Covid might encounter side effect which could impact you every day

Authors: Terri-Ann Williams Published: 11:08 ET, Nov 22 2022 The Sun

IF you’ve had Covid-19 then you could be plagued by memory issues, researchers have warned.

Experts at Hull York Medical School said memory function can improve over time, but that those with ongoing Covid symptoms could continue to experience issues.

This is also known as long Covid, with many Brits suffering with the condition, which includes symptoms such as anxiety, brain fog and severe fatigue.

Medics said that it’s widely known the virus can cause respiratory issues, but that memory issues aren’t as well researched.

The experts used an online anonymous survey which included a memory quiz.

Over 5,400 people took part between December 2020 and July 2021, with around 31 per cent having had one Covid infection during that time.

The factors which significantly affected memory scores were found to be Covid-19 status, age, time post-Covid and whether individuals were experiencing ongoing symptoms.

Experts also looked at memory scores and found that those over the age of 25 had a decline in function.

Writing in Plos One, they said that memory scores gradually increased over a period of 17 months post-Covid.

However, those with ongoing symptoms continued to show a reduction in memory scores.

How COVID-19 causes neurological damage

Authors: Date:nnNovember 14, 2022 University of Basel

Summary:It’s not uncommon for people to lose their sense of taste and smell due to a COVID-19 infection. In others, the disease has had an even stronger impact on the nervous system, with effects ranging from lasting concentration problems to strokes. Now, researchers have reported new insights into the development of ‘neuro-COVID’.

It’s not uncommon for people to lose their sense of taste and smell due to a Covid-19 infection. In others, the disease has had an even stronger impact on the nervous system, with effects ranging from lasting concentration problems to strokes. Now, researchers led by Professor Gregor Hutter from the Department of Biomedicine at the University of Basel and University Hospital of Basel have reported new insights into the development of “neuro-Covid” in the journal Nature Communications.

Specifically, the team investigated how different severities of neuro-COVID can be detected and predicted by analyzing the cerebrospinal fluid and blood plasma of affected individuals. Their findings also offer some indications of how to prevent neurological damage due to Covid-19.

The study included 40 Covid-19 patients with differing degrees of neurological symptoms. In order to identify typical changes associated with neuro-Covid, the team of researchers compared these individuals’ cerebrospinal fluid and blood plasma with samples from a control group. They also measured the brain structures of test subjects and surveyed participants 13 months after their illness in order to identify any lasting symptoms.

Holes in the blood-brain barrier

Particularly in the group with the most serious neurological symptoms, the researchers identified a link with an excessive immune response. On the one hand, affected individuals showed indications of impairment of the blood-brain barrier, which the study’s authors speculate was probably triggered by a “cytokine storm” — a massive release of pro-inflammatory factors in response to the virus.

On the other hand, the researchers also found antibodies that targeted parts of the body’s own cells — in other words, signs of an autoimmune reaction — as a result of the excessive immune response. “We suspect that these antibodies cross the porous blood-brain barrier into the brain, where they cause damage,” explains Hutter. They also identified excessive activation of the immune cells specifically responsible for the brain — the microglia.

Blood test as a long-term objective

In a further step, Hutter and his team investigated whether the severity of neurological symptoms is also perceptible in brain structures. Indeed, they found that people with serious neuro-Covid symptoms had a lower brain volume than healthy participants at specific locations in the brain and particularly at the olfactory cortex — that is, the area of the brain responsible for smell.

“We were able to link the signature of certain molecules in the blood and cerebrospinal fluid to an overwhelming immune response in the brain and reduced brain volume in certain areas, as well as neurological symptoms,” says Hutter, adding that it is now important to examine these biomarkers in a greater number of participants. The aim would be to develop a blood test that can already predict serious cases, including neuro-Covid and long Covid, at the start of an infection.

Targets for preventing consequential damage

These same biomarkers point to potential targets for drugs aimed at preventing consequential damage due to a Covid-19 infection. One of the biomarkers identified in blood, the factor MCP-3, plays a key role in the excessive immune response, and Hutter believes there is the potential to inhibit this factor medicinally.

“In our study, we show how coronavirus can affect the brain,” he says. “The virus triggers such a strong inflammatory response in the body that it spills over to the central nervous system. This can disrupt the cellular integrity of the brain.” Accordingly, Hutter says that the primary objective must be to identify and halt the excessive immune response at an early stage.

Journal Reference:

  1. Manina M. Etter, Tomás A. Martins, Laila Kulsvehagen, Elisabeth Pössnecker, Wandrille Duchemin, Sabrina Hogan, Gretel Sanabria-Diaz, Jannis Müller, Alessio Chiappini, Jonathan Rychen, Noëmi Eberhard, Raphael Guzman, Luigi Mariani, Lester Melie-Garcia, Emanuela Keller, Ilijas Jelcic, Hans Pargger, Martin Siegemund, Jens Kuhle, Johanna Oechtering, Caroline Eich, Alexandar Tzankov, Matthias S. Matter, Sarp Uzun, Özgür Yaldizli, Johanna M. Lieb, Marios-Nikos Psychogios, Karoline Leuzinger, Hans H. Hirsch, Cristina Granziera, Anne-Katrin Pröbstel, Gregor Hutter. Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional studyNature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-34068-0

Pathophysiology and Management of Tongue Involvement in COVID-19 Patients

Authors: Zeinab Mohseni AfsharMohammad BararySoheil EbrahimpourAlireza JanbakhshMandana AfsharianAmirhossein Hasanpour & Arefeh Babazadeh Indian Journal of Otolaryngology and Head & Neck Surgery (2022)

Abstract

Evaluate the lingual manifestations of COVID-19, and provide a clinical guide in managing these symptoms. Electronic databases, such as PubMed/Medline, and Scopus were searched until November 1, 2020, and only randomized controlled trials, cross-sectional and cohort studies, as well as case reports and series, and review articles in English were considered. A total of 40 studies were included in this study. Lingual involvement has been extensively reported in patients with coronavirus disease 2019 (COVID-19). The most common features of lingual involvements were red or light red, yellow coating, and greasy coating tongue, though other complications, such as pale, purple, white coating, grayish-black coating, rough, tender, puffy, spotty, prickles, fissured, and tooth-marked tongue was also reported. Poor oral hygiene, opportunistic infections (OIs), medications, and hyper-inflammatory response to infection are the most common predisposing factors for the onset of oral lesions in patients with COVID-19. In conclusion, the current review described the lingual manifestations of COVID-19, and as oral complaints are relatively common in COVID-19 patients, an intraoral examination should be conducted in all suspected cases of SARS-CoV-2 infection.

Introduction

While respiratory and gastrointestinal complications were the main manifestations of coronavirus disease 2019 (COVID-19), many more manifestations became apparent as the pandemic progressed [1]. Lingual involvement has been extensively reported in COVID-19 patients. The most primary features are chemosensory disorders, such as smell and taste problems [2]. These complications frequently happen during many viral infections, such as influenza [3].

Tongue Features in COVID-19

Chemo-sensory disorders can be defined as diseases related to the sense of taste and smell. Taste disturbances can be categorized as quantitative and qualitative disorders. Hypogeusia, a diminished sense of taste, and ageusia, or the absence of taste, are examples of quantitative taste problems, while dysgeusia is a qualitative change in taste perception [4]. Temporary taste changes may be the sole manifestation of COVID-19 [5]. Dry mouth or xerostomia, which is reported in several patients due to hyposalivation or decreased saliva production [6], is associated with taste disturbances [7] and is manifested by an increased need for drinking fluids in patients with COVID-19 [8]. Some of these patients may even experience tongue burns or spicy, salty, sour, sweet taste, or even dysgeusia [9]. The tongue’s blisters, scattered reddish macules on the tongue [10], ulcers, and the tongue’s painful inflammation have also been reported [11].

Moreover, COVID-19 has been attributed to a Kawasaki-like disease with glossitis, also called red strawberry tongue [12]. Furthermore, the tongue can also be involved as a component of angioedema in the context of COVID-19 [13]. A new feature of COVID-19 has been reported in a patient presenting with Melkersson-Rosenthal syndrome (MRS), a triad of orofacial edema, facial paralysis, and fissured tongue [14].

Different medications used to treat COVID-19, such as remdesivir, favipiravir, ribavirin, and lopinavir/ritonavir, can also cause xerostomia and taste disorders [1516]. Also, chloroquine has been reported to be linked to transient oral pigmentations [17]. Moreover, azithromycin played a role in tongue discoloration and oral candidiasis [18]. Furthermore, intensive care unit (ICU) admitted patients who have been intubated routinely develop tongue coatings and candidiasis [19].

The tongue features of COVID-19 have been investigated in several studies, particularly in traditional Chinese medicine. Changes in tongue characteristics are correlated to the progression and severity of the disease [20]. The shape, color, and coating of the tongue, and color and thickness of the fur, are among the characteristics studied previously. The most common subjective characteristics of lingual involvement were red or light red tongue, yellow coating, and greasy coating. However, the pale tongue, purple tongue, white coating, grayish-black coating, rough tongue, tender tongue, puffy tongue, spots, prickles tongue, fissured tongue, and tooth-marked tongue were also reported [21]. Interestingly patients with milder COVID-19 had thinner tongues with lighter colors, while in patients with more severe disease, thicker coatings, more tender and purplish tongues were observed [22]. Figure 1 illustrates the extrapulmonary manifestations of COVID-19, and a patient with COVID-19 who manifested with erythematous tongue with deep grooves is presented.

figure 1
Fig. 1

Black hairy tongue (BHT) or lingua villosa nigra is quite commonly demonstrated in the COVID-19 setting. It is a painless and benign disorder due to the lack of desquamation and increased proliferation and hypertrophy of the tongue’s filiform papillae, leading to a black, sometimes brown, yellow, or green discoloration of the tongue, halitosis, and a metallic taste [23]. Several underlying conditions have been suggested to lead to this disorder, which include antibiotics, such as bismuth [24], amoxicillin [25], tetracycline [26], linezolid [27], and psychotropic agents, including olanzapine, phenothiazines, and tricyclic antidepressants [28]. Dehydration decreased saliva production, trigeminal neuralgia, poor oral hygiene, smoking, alcoholism, and infections were also observed to trigger this condition [29]. BHT may be asymptomatic or cause nausea, halitosis, or dysgeusia [30].

Pathophysiology of Tongue Involvement

In addition to the respiratory and gastrointestinal tract, the angiotensin-converting enzyme 2 (ACE2), which is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor in the human body, is also expressed in the epithelium of the oral cavity, including the epithelial cells of the tongue [31]. ACE2 receptors are more densely located on the tongue’s dorsum, where the epithelium is significantly altered during COVID-19 and predisposes to overgrowth of anaerobic bacteria, leading to halitosis [32]. Any infectious or inflammatory conditions can lead to hyposalivation due to disturbed salivary secretion, and infection with SARS-CoV-2 can also initiate this process [33].

Dysgeusia and xerostomia may be due to nasal congestion and rhinorrhea caused by oral respiration in viral infections of the upper respiratory [34]. However, in the context of SARS-CoV-2 infection, they are attributed to an olfactory malfunction or neurological impairment [35]. Taste damage results in dysgeusia and ageusia mainly due to an underlying olfactory disturbance, but sometimes primary taste impairment may occur in the context of COVIDjav-19 [36]. The distribution of oral microbiota equilibrium caused by systemic drugs used in COVID-19 may also have a role in oral manifestations and, in particular, halitosis [37]. The pathophysiology of tongue color changes can be microcirculation damage, decreased arterial pressure of oxygen, and increased platelet aggregation [22].

Moreover, the yellow discoloration of the tongue can be attributed to fever and infection, which is correlated with lung damage severity [38]. Furthermore, the tongue’s greasy coatings may indicate either damage to the free oxygen radicals scavenger system or dysbiosis, which latter is a decrease in the levels of Lactobacillus and Bifidobacterium [39]. Besides, the tongue’s tenderness reflects organ failure within the context of a systemic disease, such as COVID-19 [40]. It should be noted that all oral lesions associated with COVID-19 are related to immunosuppression and physical stress [17].

Management of COVID-19 Patients with Tongue Involvements

Most of the lingual problems and taste disturbances subside spontaneously [41]. Nevertheless, some may need specialized treatment, like immunoglobulin and corticosteroids for the Kawasaki-like disease [42] or antihistamines and corticosteroids for angioedema [13]. BHT management increases hydration, induces salivation, discontinues tobacco or alcohol use, and other predisposing factors [43]. If ineffective, gentle tongue cleaning with a brush, topical retinoids or salicylic acid, keratolytic agents, or surgical excision may be curative [44].

Conclusion

The current COVID-19 pandemic is unique because of the diverse multi-organ manifestations it has presented. Taste disturbances and tongue changes are among the various characteristics of SARS-CoV-2 infection. Therefore, because oral complaints are relatively common in COVID-19 patients, an intraoral examination should be conducted in all suspected cases of SARS-CoV-2 infection.

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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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). 

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
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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.

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)

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Impact of Systemic Diseases on Olfactory Function in COVID-19 Infected Patients

Authors: Ayat A Awwad,1 Osama MM Abd Elhay,2 Moustafa M Rabie,3 Eman A Awad,4 Fatma M Kotb,4 Hend M Maghraby,4 Rmadan H Eldamarawy,4 Yahia MA Dawood,1 Mostafa IEI Balat,1 Ahmed IM Hasan,5 Ahmed H Elsheshiny,6 Said SMM El Sayed,2 Albayoumi AB Fouda,2 Ahmad MF Alkot2 DovPress November 7, 2022

1Otorhinolaryngology department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 2Medical Physiology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 3Public Health and Community Medicine Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 4Internal medicine department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 5Pediatric Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 6Neurology department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

Correspondence: Ayat A Awwad, Otorhinolaryngology department, Faculty of Medicine, Al-Azhar University, Al Zhraa University Hhospital, Alabasia, Cairo, 11517, Egypt, Email ayatnasr7419@yahoo.com; dr.ayat@azhar.edu.eg Osama MM Abd Elhay, Medical Physiology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt, Email osama.m.m.abdelhay@gmail.com; osamaabdelhay@domazhermedicine.edu.eg

Background: COVID-19 (SARS-CoV-2/2019-nCoV) is now a major public health threat to the world. Olfactory dysfunctions (ODs) are considered potential indicating symptoms and early case identification triaging for coronavirus disease 2019 (COVID-19). The most common reported comorbidities are diabetes mellitus, chronic lung disease, and cardiovascular disease. The objective of this study was to evaluate prevalence of different types of smell disorders in patients with laboratory-confirmed COVID-19 infection and impact of involved systemic diseases.
Methodology: A cross-sectional retrospective study has been done for patients with laboratory-confirmed COVID-19 infection (mild-to-moderate). The data collected from patient’s files and developed online electronic questionnaire (WhatsApp) based on the patients most common and recurrent reported data including: a) symptoms of olfactory dysfunction and associated covid19 symptoms fever and headache, cough, sore throat, pneumonia, nausea, vomiting and diarrhea, arthralgia and myalgia and taste dysfunction. b) Associated systemic diseases including: diabetes, hypertension, asthma, chronic renal disease, chorionic liver disease and hypothyroidism.
Results: Of 308 patients confirmed with Covid-19 infection, (72.4%) developed OD distributed as follows; complete anosmia (57.8%), troposmia (8.4%), hyposmia (2.9%), partial anosmia (2.6%) and euosmia (0.6%). Significantly increased prevalence of diabetes, hypertension asthma in the group with olfactory dysfunction (p < 0.001), chronic liver disease (p = 0.005), and hypothyroidism (p = 0.03).
Conclusion: The development of ODs after Covid-19 infection was associated with mild disease form and lower hospitalization. In addition, it showed significant relationship with preexisting systemic diseases. Anosmia is the common modality of ODs.

Keywords: COVID-19, anosmia, olfactory dysfunction

Introduction

World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) to be pandemic after it quickly spread all over the world.1 The involved cause is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).2 Human-to-human transmission is extremely rapid.3 Coronavirus is contagious with an incubation period ranging from 2 to 14 days. Through this period, patients can transmit infection even if asymptomatic.4

Asia reported that the most prevalent symptoms as: fever, myalgia, arthralgia cough, dyspnea, headache, diarrhea, rhinorrhea, and sore throat.5 Also, respiratory complications as pneumonia, lung fibrosis, and even death have been reported.6 Later, atypical presentation of the disease is widely observed including olfactory and gustatory malfunction but without rhinorrhea or nasal obstruction which are usually associated to other respiratory viral infections.7

WHO considers smell disorders as key symptoms of COVID-19.8 The American Academy of Otolaryngology–Head and Neck Surgery Foundation, 20209 together with Ear, Nose, and Throat Society of the United Kingdom (ENTUK) recommended self-isolation for patients presenting with these clinical features. Many countries reported the association smell disorder and taste with COVID-1910–12, but evidence remains controversial. In addition, none of them was concerned the incidence of different types of dysfunction.

COVID-19 virus appears to be more severe in severe older people and people with systemic conditions (such as diabetes, hypertension and asthma).13

The previous studies confirmed on olfactory dysfunction alone, neither its types nor impact of chronic diseases on OD so the aim of this study is to evaluate prevalence of different types of smell disorders in patients with laboratory-confirmed COVID-19 infection and impact of involved systemic diseases on ODs.

Methodology

The study was approved from Ethical Committee of the Faculty of medicine of Al-Azhar University (IRP) which complies with the Declaration of Helsinki. A cross-sectional retrospective study to patients with laboratory-confirmed COVID-19 infection (mild-to-moderate) who admitted in Al – Azhar University hospitals, fever hospitals, in addition to some of our patient’s clinics in Cairo, Egypt between the period from June 2020 to December 2020. The patients were divided into asymptomatic and symptomatic. The severity of the symptomatic diseases was classified into mild, moderate and severe.14

Informed consent was obtained from all patients (or a parent or legal guardian of patients under 18 years of age). The data collected from patient’s files and developed online electronic questionnaire (WhatsApp). Electronic questionnaire was designed by Professional otorhinolaryngologist, so that each participant could complete the survey. Questionnaire was based the patients most common and recurrent reported data including:

  • 4 items for assessment of ODs including: presence of smell dysfunction (yes or no), types of smell dysfunction (anosmia, hyposmia, partial anosmia, euosmia and troposmia).
  • 8 items for symptoms associated with covid-19 including: fever, headache, cough, sore throat, pneumonia, nausea, vomiting, diarrhea, arthralgia, myalgia and taste dysfunction (yes/no)
  • 6 items for associated systemic diseases including: diabetes, hypertension, asthma, chronic renal disease, chorionic liver disease and hypothyroidism (yes or no)

Inclusion criteria were: (> 12 years old of both genders); laboratory-confirmed COVID-19 infection (reverse transcription polymerase chain reaction, RT-PCR); native speaker patients, and patients clinically able to fulfill the questionnaire.

Patients with history of smell disorders, and not confirmed COVID-19, were unable to fulfill the questionnaire in addition to patients admitted to intensive care were also excluded from the study.

The data were collected, tabulated, and analyzed by Statistical Package for Social Sciences (version 21; SPSS Inc., Chicago, IL, USA). Two types of statistics were done:

  • Descriptive statistics [eg percentage (%), mean (x) and standard deviation (SD)],
  • Analytic statistics: which include the following:
    1. Chi-square test (χ2): was used to indicate presence or absence of a statistically significant difference between two qualitative variables.
    2. P-value of <0.05 was considered statistically significant.

Results

Demographic characteristics, comorbidities, and symptoms at the onset were reported in all patients confirmed with COVID-19 as shown in Table 1.

Table 1 Characteristics of Study Participants (N = 308)

The prevalence of ODs were 72% (223) with anosmia being the most common presented type (57.8%) while euosmia was the least presented type being only in (0.6%) as shown in Table 2 and Figure 1.

Table 2 Prevalence of Different Types of Olfactory Dysfunction Among COVID-19 Infected Patients (N = 308)

Figure 1 Prevalence of olfactory dysfunction types among cases who suffers from this dysfunction.

The frequency of ODs were significantly high with increasing in age (P value =0.000). But there was no significant difference between genders (P value =0.167) as reported in Table 3. Significant increases in different types of ODs with increasing in age (P value =0.000) while, there was no significant difference regarding gender (P value = 0.564) as shown in Table 4. Anosmia was the commonest presenting type of smell dysfunction in both genders (Figure 2).

Table 3 Frequency Distribution of Olfactory Dysfunction Occurrence According to Age and Sex

Table 4 Frequency Distribution of Olfactory Dysfunction Types in Relation to Age and Sex

Figure 2 Percent distribution of olfactory dysfunction types according to sex.

Regarding to other symptoms, the frequency of ODs were significantly associated to fever and headache, arthralgia, myalgia, taste dysfunction (P value =0.000), cough (P value =0.001), sore throat (P value =0.037), diarrhea, nausea and vomiting (P value =0.002). But it was not significantly associated with Pneumonia (P value =0.077) as shown in Table 5. ODs were the only presenting symptoms in 59.7% of patients Figure 3.

Table 5 Frequency Distribution of Olfactory Dysfunction Occurrence According to the Other Symptoms Experienced

Figure 3 Percent distribution of olfactory dysfunction as the only presenting symptom.

The frequency of ODs were significantly associated with diabetes, hypertension, asthma (P value=0.000), chronic liver disease, hypothyroidism (P value =0.003) and chronic renal disease (P value =0.005) as reported in Table 6. The different types of smell dysfunction showed significant association with asthma, chronic renal disease (P value =0.000), diabetes (P value =0.003), and hypertension (P value =0.002) while, there was no significant association with chronic liver disease and hypothyroidism (P value =0.158 and 0.524 respectively). Anosmia was the most common type of OD in association with diabetes, hypertension, asthma and chronic liver disease while, troposmia was the most common type of OD associated with chronic renal disease. The only case presented with euosmia was reported in chronic liver disease Table 7.

Table 6 Frequency Distribution of Olfactory Dysfunction Occurrence According to the Different Comorbidities

Table 7 Frequency Distribution of Olfactory Dysfunction Types in Relation to the Comorbidities

Discussion

The CDC (Center for Disease Control and Prevention) has highlighted the loss of smell as a significant symptom of COVID-19. In addition, recent research has indicated that OD may serve as an early clinical manifestation of this contagious.15–17

The current study was conducted to study the prevalence of different types of olfactory disorders in patients with laboratory-confirmed COVID-19 infection and its relationship with preexisting systemic comorbidities. Handling the effects of systemic comorbidities on olfactory manifestations in Covid-19 patients is poorly discussed in the literature. This poses a strong point in favor of our study.

We included a total of 308 patients confirmed with Covid-19 infection, 223 patients from them developed olfactory dysfunction (72.4%). When analyzing OD encountered in our research, it was distributed as follows; complete anosmia (57.8%), troposmia (8.4%), hyposmia (2.9%), partial anosmia (2.6%) and euosmia (0.6%). This is in line with multiple previous studies which reported that smell alternations are frequent manifestations of Covid-19 infection, with a prevalence ranging from 19.4% to 88%.3,12,13

This prevalence appears to be widely different between different studies. Mao et al reported lower prevalence (5%) in China18 and Marzano et al (18%) in Italy.19 Others reported much higher prevalence, reaching up to 98% in the study of Moein et al20 and 100% in the study of Heidari et al21 in Iran. This great heterogenicity could be explained by different sample sizes, patient characteristics, and methods of evaluating OD. In addition, Meng et al22 reported the difference of incidence in different countries as COVID-19 has three central variants A, B and C. Variants A and C which affect the nasal cavity causing OD were prevalent in Europe and America. Beside, human species affects significantly the susceptibility for infection.

Brann et al23 suggested that OD associated with Covid-19 infection is due to viral invasion of olfactory epithelial cells and vascular pericytes, which will negatively impact olfactory neuronal function. Additionally, nasal inflammation, congestion, and swelling may prevent olfactory molecules from reaching the olfactory cleft. Therefore, this conductive malfunction may play a role in developing OD.24

Lechien et al25 study handling the same perspective, the encountered OD was distributed as follows; anosmia (79.6%), while the remaining cases had hyposmia (20.4%). In another study, Vaira et al26 reported that among the Covid patients diagnosed with olfactory dysfunction, mild, moderate, and severe hyposmia was detected in 76, 59, and 45 patients, respectively. In addition, the remaining 61 cases had anosmia. It is expected to find some differences between different studies regarding the type of olfactory function diagnosed, according to the sample population included and criteria used to define each type.

In the current study, a significant difference was noted between patients with and without OD regarding patient age (p < 0.001), which tended to be significantly younger in the OD group. On the contrary a previous meta-analysis by Desiato et al17 has against this relationship. Several mechanisms could explain this association between advancing age and declining olfactory function including, nasal epithelial atrophy, olfactory bulb shrinkage, cribriform plate changes, in addition to age-associated cortical degeneration.27–29,30

However, another study by Mercante et al31 reported that the severity of OD was significantly increased in younger individuals, while older ones expressed mild or no symptoms. This confirms our findings.

Our findings showed no significant impact of gender on the development of this complication (p = 0.167). Thakur et al25 confirmed the previous findings regarding the insignificant association between gender and OD (p = 0.59). On the other hand, a recent meta-analysis by Saniasiaya et al32 had shown that the female gender is a risk factor for this manifestation, as it showed higher predominance compared to men. Researchers attributed that finding to the sex-related difference in the inflammatory process.33 Additionally, female patients were more sensitive than males to detect small alternations.32

Our findings showed a significant association between OD and fever, which is more prevalent in patients with this complication. In accordance with the previous results, Lechien et al25 reported a significant positive association between OD and fever (p < 0.001).

In the current study, the headache was significantly more prevalent in patients with OD (p < 0.001). This coincides with multiple previous studies which confirmed the association between headache and olfactory disturbances.34,35 This association was explained by either CNS involvement by the virus itself or hypoxic headache, which results from nasal congestion, which is associated with a decrease in olfactory function.36,37

In our study, taste dysfunction was significantly more encountered in patients with olfactory disturbances. This was confirmed before; as Lechien et al26 reported a significant positive association between both olfactory and gustatory functions (p < 0.001). Also Speth et al38 confirmed the previous findings.

In the current study, one could notice the significantly higher prevalence of other clinical findings (including sore throat, cough, diarrhea, nausea, vomiting, arthralgia, and myalgia) in association with OD.

Likewise, Talavera et al39 also reported the significant relationship between anosmia, myalgia, and cough in patients with Covid disease (p = 0.006). Nevertheless, other manifestations did not express a significant association with olfactory disturbances (p > 0.05).

Conversely, Yan et al12 reported that olfactory dysfunction was associated with a mild disease form. Moreover, another study Izquierdo-Domínguez et al40 reported that the same dysfunction was associated with lower C-reactive protein levels and a lower need for hospitalization.

Our findings showed significantly increased diabetes prevalence in the group with OD (p < 0.001). Although there is a paucity of studies handling the link between diabetes and OD in Covid-19 patients, the association between diabetes and the development of such dysfunction is well documented in a recent meta-analysis by Kim et al.41

Multiple mechanisms could induce this, including olfactory neurodegeneration and diabetes-associated microvascular disease.22,42,43 Of course, with the presence of these diabetes-associated factors, catching Covid-19 infection will increase the chance of having that dysfunction, especially in diabetic personnel. It was previously reported that the diabetic population is at high risk of having OD compared to healthy controls (OR = 1.58).41 In contrast to the previous findings, Talavera et al39 noted no significant impact of diabetes on the development of anosmia (p = 0.448). It was present in 17.1% and 20.5% of patients with and without anosmia, respectively.

Our findings showed that olfactory disturbances were significantly associated with hypertension (p < 0.001). Hypertension was present in 23.3% and 3.5% of patients with and without this dysfunction. We are the first researchers to report that finding in Covid-19 patients to the best of our knowledge. Our finding is supported by the accumulating evidence supporting the association between OD and cardiovascular disease.44,45 Several theories could explain this association; cardiovascular disease is common in the elderly, which is associated with degenerative neuronal changes, as discussed before. Also, the proinflammatory cytokines present with atherosclerosis could decrease olfactory function. Furthermore, some cardiovascular medications have a negative impact on hearing.46,47,48

In a recent study conducted in 2021, hypertensive patients expressed a lower prevalence of OD (p < 0.001), which was present in 74.9% and 88% of patients without and with hypertension, respectively.3 This is in contrast with our findings. In fact, the role of hypertension and the potential intake of angiotensin-converting enzyme inhibitors in the development of OD need to be well discussed in the upcoming studies.

In the current study, the prevalence of asthma showed a significant increase in patients with OD (p < 0.001). Asthma and olfactory impairment have never been linked, according to a recent report published in 2021 by Rhyou et al.48 However, the presence of allergic rhinitis or sinusitis in association with asthma surely decreases the olfactory sensation.29,49

Another study negated any significant difference between the anosmia and non-anosmia groups regarding the prevalence of respiratory diseases, which was present in 19.9% and 27% of patients in the same groups, respectively (p = 0.109).39

Our findings showed a higher prevalence of chronic liver disease in association with anosmia (p = 0.003). Previously, Heiser et al50 reported that olfactory deficits are frequently encountered in patients with cirrhosis. This functional decline is the result of calorie, protein, and micronutrient deficiency in such patients.51 This evidence was supported by the improvement of this function after liver transplantation, as reported by Bloomfield et al.52

In the current study, the prevalence of chronic kidney disease was significantly higher in association with OD (p = 0.005). In fact, patients with such comorbidities often complain of olfactory impairment, which could be the consequence of malnutrition and decreased fluid intake.53,54 Uremia itself could induce neuropathy and decreased smell sensation.54

Our findings showed that hypothyroidism was significantly more common in the OD group (p = 0.03). In line with the previous findings, Tsivgoulis et al55 have reported that hypothyroidism is associated with more prolonged Covid-19 induced anosmia. Sorrily, there is no clear data about whether hypothyroidism can induce OD in adult humans.56

Our study has some limitations; we should have evaluated the impact of OD on patient outcome and long-term nasal function. In addition to this retrospective study may together have some bias to mention. This study did not perform an objective olfactory test on the patients but was based on an electronic questionnaire, which may affect the accuracy of the survey.

All in all, based on our findings, complete anosmia was the most presented modality of OD. Fever, headache, taste dysfunction, sore throat, cough, diarrhea, nausea, vomiting, arthralgia, and myalgia were common symptoms associated with OD. Mild disease form, low C-reactive protein and lower need for hospitalization were common association with OD. Significant increases in incidence of OD in diabetes mellitus, hypertension, bronchial asthma, chronic liver disease, chronic kidney disease and hypothyroidism. Lower incidence of respiratory symptoms in anosmia compared to non-anosmia group.

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31. Mercante G, Ferreli F, De Virgilio A, et al. Prevalence of taste and smell dysfunction in coronavirus disease 2019. JAMA Otolaryngol Head Neck Surg. 2020;146(8):723–728. doi:10.1001/jamaoto.2020.1155

32. Saniasiaya J, Islam MA, Abdullah B. Prevalence of olfactory dysfunction in coronavirus disease 2019 (COVID-19): a meta-analysis of 27,492 patients. Laryngoscope. 2021;131(4):865–878. doi:10.1002/lary.29286

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34. Sedaghat AR, Gengler I, Speth MM. Olfactory dysfunction: a highly prevalent symptom of COVID-19 with public health significance. Otolaryngol Head Neck Surg. 2020;163(1):12–15. doi:10.1177/0194599820926464

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36. Hatton CF, Duncan CJA. Microglia are essential to protective antiviral immunity: lessons from mouse models of viral encephalitis. Front Immunol. 2019;10:2656. doi:10.3389/fimmu.2019.02656

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38. Speth MM, Singer-Cornelius T, Oberle M, Gengler I, Brockmeier SJ, Sedaghat AR. Olfactory dysfunction and sinonasal symptomatology in COVID-19: prevalence, severity, timing, and associated characteristics. Otolaryngol Head Neck Surg. 2020;163(1):114–120. doi:10.1177/0194599820929185

39. Talavera B, García-Azorín D, Martínez-Pías E, et al. Anosmia is associated with lower in-hospital mortality in COVID-19. J Neurol Sci. 2020;419:117163. doi:10.1016/j.jns.2020.117163

40. Izquierdo-Domínguez A, Rojas-Lechuga MJ, Chiesa-Estomba C, et al. Smell and taste dysfunction in COVID-19 is associated with younger age in ambulatory settings: a multicenter cross-sectional study. J Investig Allergol Clin Immunol. 2020;30(5):346–357. doi:10.18176/jiaci.0595

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What Is COVID Tongue, and What Does It Mean?

Authors: Medically reviewed by Elizabeth Thottacherry, MD — By S. Behring — Updated on January 20, 2022 HealthLine

In March 2020, the World Health Organization (WHO) declared a pandemic in response to the spread of the COVID-19 infection.

Since then, more than 50 million casesTrusted Source occurred in the United States alone. Medical professionals gathered data to determine the symptoms of COVID-19. The early symptoms observed included fatigue, shortness of breath, and fever.

But as COVID-19 cases continue, new symptoms are documented, including a rare symptom known as COVID tongue. People with COVID tongue have swollen tongues that might develop bumps, ulcers, and white patches. Read on to learn more about this unusual COVID-19 symptom.

What is COVID tongue?

Along with the more well-known symptoms of COVID-19, some people experience bumps, ulcers, swelling, and inflammation of the tongue. This is known as “COVID tongue.”

People with COVID tongue might notice that the top of their tongue looks white and patchy, or that their tongue looks red and feels swollen. They sometimes find bumps or open areas called ulcers on their tongue. Additionally, many people with COVID tongue report experiencing a loss of taste and a burning sensation in their mouth.

2021 study documented COVID tongue as a possible COVID-19 symptom. But just like many things about COVID-19, there’s a lot we don’t know right now about COVID tongue.

What’s happening inside your body to cause COVID tongue?

Another reason there are many questions about COVID tongue is that there are several possible causes. It’s common for illnesses and infections to cause changes to your tongue.

What looks like COVID tongue could easily be a symptom of a different viral or bacterial infection. Even when the bumps and swelling are clearly connected to COVID, there are many possible reasons. COVID tongue might be caused by:

  • A high number of ACE receptors in your tongue. ACE receptors are proteins found on cells in your body. When the virus that causes COVID-19, SARS-CoV-2, attaches to ACE receptors, it can get into your cells. You have many ACE receptors in your tongue, which could lead to swellingTrusted Source when you have a COVID-19 infection.
  • Your immune system fighting COVID-19. When your immune system is fighting a bacterial or viral infection, it can cause swelling throughout your body. This could include the tongue swelling associated with COVID tongue.
  • COVID-causing oral thrush. Oral thrush is a fungus in your mouth that can be caused by a number of infections. This might include COVID-19. Plus, oral thrush is a side effect of some medications used to treat COVID-19.
  • Changes to the surface of your tongue. Infections sometimes lead to changes on the surface of your tongue, such as mouth ulcers and other symptoms. It’s possible COVID-19 can lead to this sort of change as well.
  • Dry mouth. COVID-19 can affect your salivary glands and cause them to secrete less saliva. This could lead to dry mouth. Research shows that dry mouth can lead to multiple other oral health concerns.
  • COVID-activating oral herpes. The inflammation caused by COVID-19 can activate other viruses in your body. This might include the herpes simplex virus, which lays dormant in your body even when you don’t have symptoms. COVID-19 could causeTrusted Source the herpes virus to activate and cause mouth ulcers.

COVID tongue could be caused by any one of these factors or by a combination of them. There’s also a chance that COVID tongue is sometimes caused by breathing tubes and other COVID treatments that could irritate your mouth and lead to a swollen tongue.

Until we know more about COVID-19, we won’t know the exact cause of COVID tongue.

How many people get COVID tongue?

Currently, scientists don’t know how rare COVID tongue is. In one small study, up to 11 percent of people hospitalized with COVID-19 had COVID tongue, but such studies are too small to make a conclusion.

As more data from hospitals around the world come in, we might get a better idea of how common COVID tongue is.

Many people with COVID-19 have mild or moderate symptoms and can recover at home. But right now, even less is known about how many people in this group develop COVID tongue. Often they recover without contacting a doctor at all, so their symptoms are never recorded.

Even when people with mild or moderate COVID-19 do seek treatment, they often wear masks or use telehealth for a video appointment. That makes it difficult for medical professionals to see their tongues and document any abnormalities.

What is the treatment for COVID tongue?

There is currently no single set treatment for COVID tongue. You might not need treatment targeted to COVID tongue. In some cases, the treatments you already receive for COVID will be enough to resolve COVID tongue.

When COVID tongue is more severe and doesn’t respond to overall treatment, you might receive specialized treatment. This could include:

  • corticosteroids or other anti-inflammatory medications to bring down tongue swelling
  • antibacterial, antiviral, or antifungal mouth rinses to treat bumps, patches, and ulcers
  • artificial saliva mouth rinses to help combat dry mouth and promote overall tongue healing
  • low level laser therapy to treat ulcers

Treatment for swollen tongue

COVID-19 may cause the tongue to swell. Tongue swelling can quickly become a medical emergency if your airway becomes blocked. If you think your tongue is swelling, seek medical attention immediately.

The treatment for a swollen tongue is designed to reduce the swelling and relieve pain and discomfort.

Treatment options for swollen tongue include:

  • over-the-counter medications such as ibuprofen (Advil)
  • prescription anti-inflammatory medications
  • medications to treat the underlying condition causing your tongue to swell

What to do if your tongue swells

Call 911 if your tongue swells and you feel like it’s harder to breathe. Do not drive yourself to the ER because your condition could worsen on the way. For many people, calling 911 means help will reach you faster than going to an ER.

  • Have someone stay with you until help arrives.
  • Contact your healthcare professional immediately if you notice that your tongue swells.
  • If you have mild tongue swelling that gets worse, contact your doctor or healthcare professional immediately for an examination.

What’s the outlook for people with COVID tongue?

It’s currently unclear whether COVID tongue is an early symptom of COVID-19, or a symptom that develops as the condition progresses.

No matter when it develops, you might also have other, more-common COVID-19 symptoms:

  • fever
  • cough
  • shortness of breath
  • fatigue
  • nausea
  • pain

Studies are being done to see if COVID tongue is an early or warning symptom.

Mild to moderate COVID-19

People with mild and moderate cases of COVID-19 usually recover at home without medical intervention. Rates of recovery are also improving for people hospitalized with COVID-19 as doctors learn how to best treat the infection.

But since COVID-19 is still a relatively new illness, we don’t know for sure right now what the long-term effects for people will be. Some symptoms of COVID-19 might linger for weeks or even months.

Geographic tongue

While research on COVID tongue is limited now, we do know that viral infections can sometimes lead to a condition called geographic tongue.

This condition causes smooth red patches with white borders to appear on your tongue and can last for months — or even years. Geographic tongue doesn’t generally cause pain or other health concerns, but flare-ups can make it difficult to eat spicy foods.

It’s currently unclear whether COVID tongue is related to geographic tongue, or whether COVID-19 can lead to geographic tongue. As more people recover from COVID-19 and more data become available, doctors will have a better understanding of COVID tongue and any possible long-term effects.

If you have COVID-19 and are experiencing any mouth or tongue health concerns, talk with your doctor.

The bottom line

Some people with COVID-19 develop bumps, white patches, and swelling on their tongues. This is known as COVID tongue and it’s still being studied.

Right now, there are a lot of unanswered questions about COVID tongue. We currently don’t know how many people get COVID tongue or what causes it. More information about COVID tongue will be available as doctors learn more about COVID tongue and more research occurs.

COVID-19 “Long-Haulers:” The Emergence of Auditory/Vestibular Problems After Medical Intervention

Authors: Robert M. DiSogra Audiology Today American Academy of Audiology

Johns Hopkins University’s Center for Systems Science and Engineering (CSSE) in the United States reported over seven million documented cases of COVID-19 and over 212,000 deaths since the virus was first identified in this country in January 2020 (2020).

Early in the pandemic, the medical profession, the Centers for Disease Control and Prevention (CDC), the National Institute of Health (NIH), and both federal and state governments worked 24/7 to develop testing protocols and intervention strategies (pharmacological management and vaccines).

Until a scientifically proven intervention strategy is identified along with a vaccine, the public continues to be advised by the CDC to wear face masks, socially distance from each other, wash their hands regularly, and avoid crowds/indoor events. This major change in our lifestyle/behavior and the associated economic impact is still with us today.

As a novel virus, no assumptions can be made about treatment or management strategies or prediction of late onset of new symptoms. Within a few months after the pandemic was declared, a variety of pharmacological interventions were proposed by the federal government—all without scientific evidence. The most popular unproven intervention strategy in the United States was the combined use of two known ototoxic drugs: hydroxychloroquine and azithromycin (Bortoli and Santiago, 2007; FDA, 2017; Prayuenyong. et al, 2020).

DiSogra (2020a) provides a detailed review of this strategy from an audiologist’s perspective. In Europe, hydroxychloroquine and chloroquine were prescribed for almost 12 percent of COVID-19 patients (Lechien et al, 2020).

Researchers attempted to determine if other FDA-approved drugs could be repurposed as an intervention strategy. A summary of several FDA-approved drugs that were being repurposed for COVID-19 patients appears in DiSogra (2020b).

Vaccines for COVID-19 are still undergoing clinical trials. The U.S. National Library of Medicine’s Clinical Trials website is monitoring over 80 COVID-19 vaccine-related clinical trials (in various phases of development) worldwide as of September 24, 2020.

COVID-19 Recovery

A self-organized group of COVID-19 “long-haul” patients, who are researchers in relevant fields (e.g., participatory design, neuroscience, public policy, data collection and analysis, human-centered design, health activism) and have intimate knowledge of COVID-19, have been working on patient-led research around the COVID experience and prolonged recoveries (Assaf et al, 2020).

To capture and share the experiences of patients suffering from prolonged or long-haul COVID-19 symptoms, survivor/researchers used a data-driven participatory-type survey and patient-centric analysis. With 640 survey respondents, many participants experienced fluctuations in the type (70 percent reporting) and intensity (89 percent reporting) of symptoms over the course of being symptomatic.

For approximately 10 percent who had recovered, the average length of time of being symptomatic was 27 days. Unrecovered respondents experienced symptoms for an average of 40 days, with a large proportion experiencing symptoms for five to seven weeks. The chance of full recovery by day 50 was smaller than 20 percent.

Most common auditory/vestibular symptoms were earaches and vertigo lasting up to eight weeks after the diagnosis. Sixty percent of the respondents reported balance issues that peaked by second week and subsided over the next four weeks. Earaches (~32 percent) and vertigo/motion sickness (~25 percent) persisted over six weeks. One patient reported hearing loss that recovered after three weeks. Subjects listed tinnitus as the second highest complaint on a write-in list of symptoms.

All patients experienced a full recovery after 90 days except for patients with pre-existing asthma. The majority of survey respondents were not hospitalized; however, a large number of participants (37.5 percent) had visited the emergency rooms or urgent care but were not admitted for further testing or overnight observation.

Auditory Symptoms After COVID-19 Treatment

For this manuscript, “auditory symptoms” is defined as hearing loss (any degree/type), earache, subjective tinnitus, or vertigo/balance problems.

Sensorineural Hearing Loss

Almufarrij et al (2020) conducted a rapid systematic review investigated audio-vestibular symptoms associated with coronavirus. They found five case reports and two cross-sectional studies that met the inclusion criteria (N=2300). No records of audio-vestibular symptoms were reported with the earlier types of coronavirus (i.e., severe-acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]).

Reports of hearing loss, tinnitus, and vertigo were rarely reported in individuals who tested positive for the SARS-CoV-2. They opined that reports of audio-vestibular symptoms in confirmed COVID-19 cases are few “with mostly minor symptoms, and the studies are of poor quality.”

Munro et al (2020) concluded that it was unclear which cases of hearing loss [and tinnitus] can be directly attributed to SARS-CoV-2 or perhaps related to the many possible causes of hearing loss associated with critical care including ototoxic mediations (Ciorba et al. 2020), local, or systematic infections, vascular disorders and auto-immune disease.

Elbiol (2020) reported only one case (N=121) of sudden hearing loss (0.6 percent). A case report of sudden hearing loss that occurred one week after hospitalization was also published by Koumpa et al (2020).

Conductive Hearing Loss

Fiden (2020) reported one COVID-19 patient with a unilateral otitis media. The conductive hearing loss was mild to moderate.

Tinnitus

Tinnitus was reported in four studies in 2020 (N = 8 patients; Cui et al, Fidan, Lechien et al, and Sun et al). The characteristics of the tinnitus and the impact on the individual were not reported.

Munro, et al (2020) followed 121 COVID-19 patients eight weeks after discharge. Sixteen (13.2 percent) patients reported a change in hearing and/or tinnitus after diagnosis of COVID-19. However, there was no pattern for the duration of the recovery.

Some patients showed no changes in tinnitus while one patient reported no tinnitus after eight weeks. There was self-reported tinnitus in eight cases with three reporting a pre-existing hearing loss. Another patient reported that their tinnitus resolved. Elibol (2020) noted that tinnitus is rarely seen in COVID-19 patients.

Liang et al (2020) attempted to identify and describe neurosensory dysfunctions (including tinnitus) of COVID-19 patients. A total of 86 patients were screened but only three (3.5 percent) were identified as having tinnitus. The average interval from onset of tinnitus was one day; while the average interval from onset of tinnitus to admission was 6 ± 5.29 days; the average duration of tinnitus was 5 ± 0 days. Finally, a non-organic component of the tinnitus (i.e., anxiety) cannot be ruled out (Xia et al, 2020). Although the current studies indicate a low incidence of tinnitus in these patients, development of tinnitus management protocol may be beneficial.

Vertigo

The Munro study (2020) identified one patient with hearing loss that also reported vertigo, which the authors concluded may have been vestibular in origin. TABLE 1 summarizes the earliest case reports and cross-sectional study designs that identified auditory/vestibular problems.

AUTHORTYPE OF STUDYNAUDITORY/VESTIBULAR SYMPTOMS
Asaaf et al, 2020Survey640Earaches (32 %)
Vertigo (60%)
Hearing Loss (0.15%)
Ciu et al, 2020Case Report20Tinnitus (N=1)
Otitis media (N=1)
Fiden, 2020Case Report1Tinnitus
Otitis media
Han et al, 2019Case Report1Vertigo
Lechien et al, 2019Cross Sectional1420Ear pain (N=358 or 25%)
Rotary vertigo (N=6 or 0.4%)
Tinnitus (N=5 or 0.3%)
Mustafa, 2020Cross Sectional20Sensorineural HL
Sriwijitalai and Wiwanitkit, 2020Case Report82Sensorineural HL (N=1 or 1.2%)
Sun et al, 2020Case Report1Sensorineural HL

TABLE 1. Summary of published case reports and cross-sectional research that identified some type of auditory/vestibular problems (adapted from Almufarrij et al, 2020).

The Mustafa study (2020) compared two groups of patients (asymptomatic SARS-CoV-2 vs. control), and the results found that the asymptomatic SARS-CoV-2 group had significantly poorer hearing thresholds at 4-8 kHz and lower amplitude transient evoked otoacoustic emissions (Mustafa, 2020). Almufarrij et al (2020) concluded that high-quality studies are required in different age groups to investigate the acute effects of coronavirus. These studies include temporary effects from medications as well as studies on long-term risks on the audio-vestibular system.

Some Intervention Strategies

Aside for re-purposed pharmaceuticals, dietary supplements are proposed as a treatment option (DiSogra, 2020c). In the Aasaf study (2020), Tylenol® (followed by an inhaler) were the top medications taken by respondents in their survey to treat symptoms. Supplements, such as vitamin C, vitamin D, zinc and electrolytes, were taken by many of the respondents over several weeks. Hot liquids were also very popular with the respondents.

Other popular entries for medications, supplements and treatments reported by participants included Mucinex®, prednisone, steroids, ginger, magnesium, steam, probiotics, oregano oil/supplements, Flonase®, and other nasal sprays.

The majority of respondents never consumed any of the following substances: smoke/vape nicotine, edible or liquid cannabis, smoke/vape recreational cannabis, consume or smoke cannabidiol-only products or consume recreational drugs. Many of the respondents said they occasionally or frequently consumed alcoholic beverages.

Conclusion

The auditory-vestibular side effects of any illness, or from a pharmaceutical, nutraceutical, noise, or trauma, as well as any psychogenic component, will always be a concern for audiologists. With COVID-19, it is still too early to predict auditory-vestibular side effects, although several studies have attempted to do so or at least guide us in our short and long-term management.

If these “long-hauler” patients can be followed more closely, a body of knowledge should emerge that will help audiologists better manage COVID-19 survivors when their auditory/vestibular symptoms result in a referral for testing. It would appear that conductive and sensorineural hearing loss, tinnitus (including its non-organic origin) and vertigo can be expected but with no predictable pattern.

Protocols for management will need to be developed; however, in the interim, an ototoxic drug monitoring protocol can serve as a reference (American Academy of Audiology, 2009). The duration of these symptoms (after the diagnosis) can last from one day to eight weeks but, again, it is still too early in the life of this pandemic to state definitively if these symptoms are temporary or permanent. Although no formal protocols have been developed, audiologists must keep in mind that the more severe, life-threatening side effects of COVID-19 will continue to get researcher’s attention.

This article is a part of the September/October 2020 Audiology Today issue.

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