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). 

Optic Neuropathy after COVID-19

Authors: Alicia ChenAndrew Go Lee, MDNagham Al-Zubidi, MDNoor LaylaniPamela Davila-Siliezar American Academy of Ophthalmology

the process is ischemic optic neuropathy (ION) and both anterior ION and posterior ION have been reported with COVID19. Clinicians should be aware of the possibility of ION in COVID19.

Contents

Background

Ischemic optic neuropathy (ION) is a sudden, painless loss of vision due to an interruption of blood supply to the optic nerve[1]. ION can be classified as anterior with disc edema (AION) or posterior without disc edema (PION). AION is typically divided into arteritic (A-AION) and non-arteritic (NA-AION) etiologies[1].

Recently, cases of optic neuropathy have been reported following infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes the Corona Virus Disease-19 (COVID19)[2] [3][4][5][6][7][8][9]. Proposed mechanisms of how SARS-CoV-2 might cause ION (AION or PION) include inducing a severe inflammatory response, endothelial damage, hypercoagulable state, and hypoxemia, which leads to hypoperfusion and subsequent ischemia of the optic nerve[3] [10][11][12][13].

Typical non-COVID19 related NA-AION is associated with risk factors: (1) structural factors which make the optic nerve head susceptible to ischemic events (e.g., small cup to disc ratio or “disc at risk”) and (2) vascular factors which predispose to acute hypoperfusion of the optic nerve head (e.g., diabetes mellitus, systemic hypertension, nocturnal arterial hypotension, ischemic heart disease, anemia)[1]. Non-arteritic posterior ischemic optic neuropathy (NA-PION) is thought to have similar vascular risk factors as NA-AION, but no structural risk has been found[14]. Typical AION is the common presentation, while PION is rare[14].

Pathophysiology of COVID19-related ION

The coronavirus has been reported to cause activation of inflammatory cells (e.g. neutrophils and monocytes) and endothelial cells leading to high levels of circulating inflammatory cytokines (e.g., CRP, ferritin, IL-2, TNF-α) and excess production of pro-coagulants (e.g., tissue factor and von Willebrand factor)[3] [11]. Extensive complement involvement and membrane attack complex-mediated microvascular endothelial cell injury have also been reported to lead to COVID19-associated coagulopathy, which can include venous, arterial, and microvascular thrombosis[12][13]. COVID19 has also been reported to cause clinically significant hypoxemia[14].

In ION, it has been hypothesized that these factors in COVID19 (inflammatory response, hypercoagulable state, and hypoxemia) may lead to thrombosis of the blood vessels (e.g., ciliary vessels) supplying the optic nerve and subsequent ischemia of the optic nerve[2][3][4][5][7][8][9]. However, there have been no studies to confirm this pathogenesis.

Savastano et al. reported the impact of SARS-CoV-2 infection on the microvascular network of optic nerve head in patients who recovered from COVID19. The study reported that in the patients who recovered from COVID19, there was an impairment in the blood supply to the peripapillary retinal nerve fiber layer, characterized by a reduction of radial peripapillary capillary plexus (RPCP) density. RPCP density has been previously correlated to visual acuity and visual field loss in NAION patients[15].

Case Reports of Presumed ION after COVID19 Infection

CaseSexAgePast Medical HistoryOphthalmic SymptomsPhysical ExamLabsDiagnosis
1[2]F50HTN, HLDAcute, painless vision loss OD; 1 week after testing positive for COVID20/70 OD. Temporal and inferior nasal field loss OD.No RAPD. Normal fundoscopic exam with no optic disc edema.Normal CBC, BMP, ESR. CRP 7 and d dimer 206 ng/ml.PION
2[3]M52NoneAcute, painless vision loss and floater OD; 2 weeks after COVID hospitalizationHand motion perception OD. RAPD OD. Central and nasal field loss OD.Pale optic disc without swelling OD, small optic disc OS.ESR 42 (high), CRP 39 (high). Lymphopenia (WBC 6800/ul; lymphocyte: 11.5%)NAION
3[4]M43DM, HLDAcute, painless vision loss OD; 4 weeks after COVID symptoms and testing positive20/30 OD. RAPD OD. Inferior hemifield defect OD. Temporal pallor of optic nerve OD.Normal CBC, ESR, BMP.NAION
4[5]M45DM, HTNAcute, blurry vision OD followed by blurry vision OS 2 weeks later; started 1 month after COVID-19 infection6/6 OD, 6/24 OS. RAPD OS. Inferior field defect OS. Superior and inferior field defects OS. Hyperemic optic disc with blurred margins (OD), pale edematous disc (OS).Normal CBC, ESR, BMP.Bilateral sequential NAION
5[6]F67CAD s/p PCI 7 years ago, HTNDecreased vision OS preceded by 2-day headache; tested positive for Sars-CoV-2 2 days later20/800 OS (with dense posterior subcapsular cataract). No RAPD. Superior visual field loss OS.Normal labsNAION
6[7]F69DM, HTNVision loss OS with severe headaches near eyes and occiput, and scalp tenderness; 2.5 weeks after positive SARS-CoV-2 testLight perception from nasal and superior side OS. No direct response and slow indirect response to light OS. Blurring of optic margins with flame hemorrhages OS.Elevated ESR (63 mm/h; range, 3-15 mm/h). Ultrasound of temporal arteries revealed wall thickening and a “halo.”GCA/AAION
7[8]M72DM, HTN, smokingAcute, painless, blurred vision OD; 13 days after COVID-19 symptoms0.3 OD. No RAPD. Inferior visual field loss OD. Optic disc swelling OD.Normal labsNAION
8[9]M64NoneVision loss OD; 5 weeks after COVID-19 symptoms and hospitalization20/20 OD. RAPD OD. Inferior visual field loss OD. Pale optic disc with sectorial papillary edema ODNormal labsNAION

Prognosis

About 40% of patients with non-COVID19 related NAION will spontaneously recover some vision[16].

Treatment

While there are no definite treatments for NAION, the underlying cause should be treated to prevent further complications. Risk factors for atherosclerosis should be controlled, including blood pressure and diabetes[16]. Most of the recommended treatments are intended to prevent thrombosis (e.g., aspirin) or reduce the edema of the optic disc [6]. While corticosteroids can lead to improvement in systemic symptoms and prevention of blindness in arteritic ION/giant cell arteritis (GCA), corticosteroids are not suggested for NAION[17]. In the context of COVID19, the benefits of steroids have not been explored[6].

Summary

Optic neuropathy has been reported in COVID19 and the mechanisms remain ill defined although several hypotheses have been proposed including inflammatory cytokines and a transient hypercoagulable state. Many authors believe that the process is ION and both AION and PION have been reported with COVID19. Further work is necessary to confirm if the optic neuropathy is truly ischemic in origin and what potential treatments might be considered. In typical AION the major diagnostic dilemma is differentiating arteritic (i.e., giant cell arteritis) from non-arteritic AION (NAION). In the setting of COVID19 infection, the acute phase reactants (e.g., ESR, CRP, platelet count) might be elevated and mistaken for signs of GCA. Evaluation for A-AION and GCA in elderly patients including temporal artery biopsy might still be necessary however and some of the cases of AION and COVID19 in the literature may have been coincidental (GCA) and not causal. Clinicians should be aware of the possibility of ION in COVID19.

References

  1. ↑ Jump up to:1.0 1.1 1.2 Hayreh S. S. (2011). Management of ischemic optic neuropathies. Indian journal of ophthalmology59(2), 123–136. https://doi.org/10.4103/0301-4738.77024
  2. ↑ Jump up to:2.0 2.1 2.2 Selvaraj V, Sacchetti D, Finn A, Dapaah-Afriyie K. (2020). Acute Vision Loss in a Patient with COVID-19. Rhode Island Medical Journal, 103(6), 37-38.
  3. ↑ Jump up to:3.0 3.1 3.2 3.3 3.4 Golabchi, K., Rezaee, A., Aghadoost, D., & Hashemipour, M. (2021). Anterior ischemic optic neuropathy as a rare manifestation of COVID-19: a case report. Future virology, 10.2217/fvl-2021-0068. https://doi.org/10.2217/fvl-2021-0068
  4. ↑ Jump up to:4.0 4.1 4.2 Rho, J., Dryden, S. C., McGuffey, C. D., Fowler, B. T., & Fleming, J. (2020). A Case of Non-Arteritic Anterior Ischemic Optic Neuropathy with COVID-19. Cureus12(12), e11950. https://doi.org/10.7759/cureus.11950
  5. ↑ Jump up to:5.0 5.1 5.2 Sanoria, A., Jain, P., Arora, R., & Bharti, N. (2022). Bilateral sequential non-arteritic optic neuropathy post-COVID-19. Indian journal of ophthalmology70(2), 676–679. https://doi.org/10.4103/ijo.IJO_2365_21
  6. ↑ Jump up to:6.0 6.1 6.2 6.3 Babazadeh, A., Barary, M., Ebrahimpour, S., Sio, T. T., & Mohseni Afshar, Z. (2022). Non-arteritic anterior ischemic optic neuropathy as an atypical feature of COVID-19: A case report. Journal francais d’ophtalmologie45(4), e171–e173. https://doi.org/10.1016/j.jfo.2021.12.001
  7. ↑ Jump up to:7.0 7.1 7.2 Szydełko-Paśko, U., Przeździecka-Dołyk, J., Kręcicka, J., Małecki, R., Misiuk-Hojło, M., & Turno-Kręcicka, A. (2022). Arteritic Anterior Ischemic Optic Neuropathy in the Course of Giant Cell Arteritis After COVID-19. The American journal of case reports23, e933471.
  8. ↑ Jump up to:8.0 8.1 8.2 Yüksel, B., Bıçak, F., Gümüş, F., & Küsbeci, T. (2021). Non-Arteritic Anterior Ischaemic Optic Neuropathy with Progressive Macular Ganglion Cell Atrophy due to COVID-19. Neuro-ophthalmology (Aeolus Press)46(2), 104–108.
  9. ↑ Jump up to:9.0 9.1 9.2 Moschetta, L., Fasolino, G., & Kuijpers, R. W. (2021). Non-arteritic anterior ischaemic optic neuropathy sequential to SARS-CoV-2 virus pneumonia: preventable by endothelial protection?. BMJ case reports14(7), e240542. https://doi.org/10.1136/bcr-2020-240542
  10.  Kaur, S., Bansal, R., Kollimuttathuillam, S., Gowda, A. M., Singh, B., Mehta, D., & Maroules, M. (2021). The looming storm: Blood and cytokines in COVID-19. Blood reviews46, 100743. https://doi.org/10.1016/j.blre.2020.100743
  11. ↑ Jump up to:11.0 11.1 Magro, C., Mulvey, J. J., Berlin, D., Nuovo, G., Salvatore, S., Harp, J., Baxter-Stoltzfus, A., & Laurence, J. (2020). Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Translational research : the journal of laboratory and clinical medicine, 220, 1–13. https://doi.org/10.1016/j.trsl.2020.04.007
  12. ↑ Jump up to:12.0 12.1 Goshua, G., Pine, A. B., Meizlish, M. L., Chang, C. H., Zhang, H., Bahel, P., Baluha, A., Bar, N., Bona, R. D., Burns, A. J., Dela Cruz, C. S., Dumont, A., Halene, S., Hwa, J., Koff, J., Menninger, H., Neparidze, N., Price, C., Siner, J. M., Tormey, C., … Lee, A. I. (2020). Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. The Lancet. Haematology7(8), e575–e582. https://doi.org/10.1016/S2352-3026(20)30216-7
  13. ↑ Jump up to:13.0 13.1 Tobin, M. J., Laghi, F., & Jubran, A. (2020). Why COVID-19 Silent Hypoxemia Is Baffling to Physicians. American journal of respiratory and critical care medicine202(3), 356–360. https://doi.org/10.1164/rccm.202006-2157CP
  14. ↑ Jump up to:14.0 14.1 14.2 Sadda SR, Nee M, Miller NR, Biousse V, Newman NJ, Kouzis A. (2001). Clinical spectrum of posterior ischemic optic neuropathy. American Journal of Ophthalmology, 132(5):743-750.
  15.  Savastano, A., Crincoli, E., Savastano, M. C., Younis, S., Gambini, G., De Vico, U., Cozzupoli, G. M., Culiersi, C., Rizzo, S., & Gemelli Against Covid-Post-Acute Care Study Group (2020). Peripapillary Retinal Vascular Involvement in Early Post-COVID-19 Patients. Journal of clinical medicine9(9), 2895. https://doi.org/10.3390/jcm9092895
  16. ↑ Jump up to:16.0 16.1 Garrity, J. (2021). Ischemic Optic Neuropathy. Merck Manual. https://www.merckmanuals.com/home/eye-disorders/optic-nerve-disorders/ischemic-optic-neuropathy
  17.  Aiello, P. D., Trautmann, J. C., McPhee, T. J., Kunselman, A. R., & Hunder, G. G. (1993). Visual prognosis in giant cell arteritis. Ophthalmology100(4), 550–555. https://doi.org/10.1016/s0161-6420(93)31608-8

Coronavirus and the Nervous System

Authors: NIH What is SARS-CoV-2 and COVID-19?

What is SARS-CoV-2 and COVID-19?

Coronaviruses are common causes of usually mild to moderate upper respiratory tract illnesses like the common cold, with symptoms that may include runny nose, fever, sore throat, cough, or a general feeling of being ill. However, a new coronavirus called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) emerged and spread to cause the COVID-19 pandemic.

COVID-19, which means Coronavirus disease 2019, is an infectious disease that can affect people of all ages in many ways. It is most dangerous when the virus spreads from the upper respiratory tract into the lungs to cause viral pneumonia and lung damage leading to Acute Respiratory Distress Syndrome (ARDS). When severe, this impairs the body’s ability to maintain critical levels of oxygen in the blood stream—which can cause multiple body systems to fail and can be fatal.

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What do we know about the effects of SARS-CoV-2 and COVID-19 on the nervous system?

Much of the research to date has focused on the acute infection and saving lives. These strategies have included preventing infection with vaccines, treating COVID-19 symptoms with medicines or antibodies, and reducing complications in infected individuals.

Research shows the many neurological symptoms of COVID-19 are likely a result of the body’s widespread immune response to infection rather than the virus directly infecting the brain or nervous system. In some people, the SARS-CoV-2 infection causes an overreactive response of the immune system which can also damage body systems. Changes in the immune system have been seen in studies of the cerebrospinal fluid, which bathes the brain, in people who have been infected by SARS-CoV-2. This includes the presence of antibodies—proteins made by the immune system to fight the virus—that may also react with the nervous system. Although still under intense investigation, there is no evidence of widespread viral infection in the brain. Scientists are still learning how the virus affects the brain and other organs in the long-term. Research is just beginning to focus on the role of autoimmune reactions and other changes that cause the set of symptoms that some people experience after their initial recovery. It is unknown if injury to the nervous system or other body organs cause lingering effects that will resolve over time, or whether COVID-19 infection sets up a more persistent or even chronic disorder.

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What are the immediate (acute) effects of SARS-CoV-2 and COVID-19 on the brain?

Most people infected with SARS-CoV-2 virus will have no or mild to moderate symptoms associated with the brain or nervous system. However, most individuals hospitalized due to the virus do have symptoms related to the brain or nervous system, most commonly including muscle aches, headaches, dizziness, and altered taste and smell. Some people with COVID-19 either initially have, or develop in the hospital, a dramatic state of confusion called delirium. Although rare, COVID-19 can cause seizures or major strokes. Muscular weakness, nerve injury, and pain syndromes are common in people who require intensive care during infections. There are also very rare reports of conditions that develop after SARS-CoV-2 infection, as they sometimes do with other types of infections. These disorders of inflammation in the nervous system include Guillain-Barré syndrome (which affects nerves), transverse myelitis (which affects the spinal cord), and acute necrotizing leukoencephalopathy (which affects the brain).

Bleeding in the brain, weakened blood vessels, and blood clots in acute infection

The SARS-CoV-2 virus attaches to a specific molecule (called a receptor) on the surface of cells in the body. This molecule is concentrated in the lung cells but is also present on certain cells that line blood vessels in the body. The infection causes some arteries and veins—including those in the brain—to  become thin, weaken, and leak. Breaks in small blood vessels have caused bleeding in the brain (so-called microbleeds) in some people with COVID-19 infection. Studies in people who have died due to COVID-19 infection show leaky blood vessels in different areas of the brain that allow water and a host of other molecules as well as blood cells that are normally excluded from the brain to move from the blood stream into the brain. This leak, as well as the resulting inflammation around blood vessels, can cause multiple small areas of damage. COVID-19 also causes blood cells to clump and form clots in arteries and veins throughout the body. These blockages reduce or block the flow of blood, oxygen, and nutrients that cells need to function and can lead to a stroke or heart attack.

stroke is a sudden interruption of continuous blood flow to the brain. A stroke occurs either when a blood vessel in the brain becomes blocked or narrowed or when a blood vessel bursts and spills blood into the brain. Strokes can damage brain cells and cause permanent disability. The blood clots and vascular (relating to the veins, capillaries, and arteries in the body) damage from COVID-19 can cause strokes even in young healthy adults who do not have the common risk factors for stroke.

COVID-19 can cause blood clots in other parts of the body, too. A blood clot in or near the heart can cause a heart attack. A heart attack or Inflammation in the heart, called myocarditis, can cause heart failure, and reduce the flow of blood to other parts of the body. A blood clot in the lungs can impair breathing and cause pain. Blood clots also can damage the kidneys and other organs.

Low levels of oxygen in the body (called hypoxia) can permanently damage the brain and other vital organs in the body. Some hospitalized individuals require artificial ventilation on respirators. To avoid chest movements that oppose use of the ventilator it may be necessary to temporarily “paralyze” the person and use anesthetic drugs to put the individual to sleep. Some individuals with severe hypoxia require artificial means of bringing oxygen into their blood stream, a technique called extra corporeal membrane oxygenation (ECMO). Hypoxia combined with these intensive care unit measure generally cause cognitive disorders that show slow recovery.

Diagnostic imaging of some people who have had COVID-19 show changes in the brain’s white matter that contains the long nerve fibers, or “wires,” over which information flows from one brain region to another. These changes may be due to a lack of oxygen in the brain, the inflammatory immune system response to the virus, injury to blood vessels, or leaky blood vessels. This “diffuse white matter disease” might contribute to cognitive difficulties in people with COVID-19. Diffuse white matter disease is not uncommon in individuals requiring intensive hospital care but it not clear if it also occurs in those with mild to moderate severity of COVID-19 illness.

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What is the typical recovery from COVID-19?

Fortunately, people who have mild to moderate symptoms typically recover in a few days or weeks. However, some  people who have had only mild or moderate symptoms of COVID-19 continue to experience dysfunction of body systems—particularly in the lungs but also possibly affecting the liver, kidneys, heart, skin, and brain and nervous system—months after their infection. In rare cases, some individuals may develop new symptoms (called sequelae) that stem from but were not present at the time of initial infection. People who require intensive care for Acute Respiratory Distress Syndrome, regardless of the cause, usually have a long period of recovery. Individuals with long-term effects, whether following mild or more severe COVID-19, have in some cases self-identified as having “long COVID” or “long haul COVID.” These long-term symptoms are included in the scientific term, Post Acute Sequelae of SARS-CoV-2 Infection (PASC).

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What are possible long-term neurological complications of COVID-19?

Researchers are following some known acute effects of the virus to determine their relationship to the post-acute complications of COVID-19 infection. These post-acute effects usually include fatigue in combination with a series of other symptoms. These may include trouble with concentration and memory, sleep disorders, fluctuating heart rate and alternating sense of feeling hot or cold, cough, shortness of breath, problems with sleep, inability to exercise to previous normal levels, feeling sick for a day or two after exercising (post-exertional malaise), and pain in muscle, joints, and chest. It is not yet known how the infection leads to these persistent symptoms and why in some individuals and not others.

Expand accordion content

Nerve damage, including peripheral neuropathy

Fatigue and post-exertional malaise

Cognitive impairment/altered mental state

Muscle, joint, and chest pain

Prolonged/lingering loss of smell (anosmia) or taste

Persistent fevers and chills

Prolonged respiratory effects and lung damage

Headaches

Sleep disturbances

Anxiety, depression, and stress post-COVID

 How do the long-term effects of SARS-CoV-2 infection/COVID-19 relate to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)?

Some of the symptom clusters reported by people still suffering months after their COVID-19 infection overlap with symptoms described by individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). People with a diagnosis of ME/CFS have wide-ranging and debilitating effects including fatigue, PEM, unrefreshing sleep, cognitive difficulties, postural orthostatic tachycardia, and joint and muscle pain. Unfortunately, many people with ME/CFS do not return to pre-disease levels of activity. The cause of ME/CFS is unknown but many people report its onset after an infectious-like illness. Rest, conserving energy, and pacing activities are important to feeling better but don’t cure the disease. Although the long-term symptoms of COVID-19 may share features with it, ME/CFS is defined by symptom-based criteria and there are no tests that confirm an ME/CFS diagnosis.

ME/CFS is not diagnosed until the key features, especially severe fatigue, post-exertional malaise, and unrefreshing sleep, are present for greater than six months. It is now becoming more apparent that following infection with SARS-CoV-2/COVID-19, some individuals may continue to exhibit these symptoms beyond six months and qualify for an ME/CFS diagnosis. It is unknown how many people will develop ME/CFS after SARS-CoV-2 infection. It is possible that many individuals with ME/CFS, and other disorders impacting the nervous system, may benefit greatly if research on the long-term effects of COVID-19 uncovers the cause of debilitating symptoms including intense fatigue, problems with memory and concentration, and pain.

Am I at a higher risk if I currently have a neurological disorder?

Much is still unknown about the coronavirus but people having one of several underlying medical conditions may have an increased risk of illness. However, not everyone with an underlying condition will be at risk of developing severe illness. People who have a neurological disorder may want to discuss their concerns with their doctors.

Because COVID-19 is a new virus, there is little information on the risk of getting the infection in people who have a neurological disorder. People with any of these conditions might be at increased risk of severe illness from COVID-19:

  • Cerebrovascular disease
  • Stroke
  • Obesity
  • Dementia
  • Diabetes
  • High blood pressure

There is evidence that COVID-19 seems to disproportionately affect some racial and ethnic populations, perhaps because of higher rates of pre-existing conditions such as heart disease, diabetes, and lung disease. Social determinants of health (such as access to health care, poverty, education, ability to remain socially distant, and where people live and work) also contribute to increased health risk and outcomes.

Can COVID-19 cause other neurological disorders?

In some people, response to the coronavirus has been shown to increase the risk of stroke, dementia, muscle and nerve damage, encephalitis, and vascular disorders. Some researchers think the unbalanced immune system caused by reacting to the coronavirus may lead to autoimmune diseases, but it’s too early to tell.

Anecdotal reports of other diseases and conditions that may be triggered by the immune system response to COVID-19 include para-infectious conditions that occur within days to a few weeks after infection:

  • Multi-system infammatory syndrome – which causes inflammation in the body’s blood vessels
  • Transverse myelitis – an inflammation of the spinal cord
  • Guillain-Barré sydrome (sometimes known as acute polyradiculoneuritis) – a rare neurological disorder which can range from brief weakness to nearly devastating paralysis, leaving the person unable to breathe independently
  • Dysautonomia – dysfunction of the autonomic nerve system, which is involved with functions such a breathing, heart rate, and temperature control
  • Acute disseminating encephalomyelitis (ADEM) – an attack on the protective myelin covering of nerve fibers in the brain and spinal cord
  • Acute necrotizing hemorrhagic encephalopathy – a rare type of brain disease that causes lesions in certain parts of the brain and bleeding (hemorrhage) that can cause tissue death (necrosis)
  • Facial nerve palsies (lack of function of a facial nerve) such as Bell’s Palsy
  • Parkinson’s disease-like symptoms have been reported in a few individuals who had no family history or early signs of the disease

Does the COVID-19 vaccine cause neurological problems?

Almost everyone should get the COVID-19 vaccination. It will help protect you from getting COVID-19. The vaccines are safe and effective and cannot give you the disease. Most side effects of the vaccine may feel like flu and are temporary and go away within a day or two. The U.S. Food and Drug Administration (FDA) continues to investigate any report of adverse consequences of the vaccine. Consult your primary care doctor or specialist if you have concerns regarding any pre-existing known allergic or other severe reactions and vaccine safety.

A recent study from the United Kingdom demonstrated an increase in Guillain-Barré Syndrome related to the Astra Zeneca COVID-19 vaccine (virally delivered) but not the Moderna (messenger RNA vaccine). Guillain-Barré syndrome (a rare neurological disorder in which the body’s immune system damages nerve cells, causing muscle weakness and sometimes paralysis) has also occurred in some people who have received the Janssen COVID-19 Vaccine (also virally delivered). In most of these people, symptoms began within weeks following receipt of the vaccine. The chance of having this occur after these  vaccines is very low, 5 per million vaccinated persons in the UK study. The chance of developing Guillain-Barré Syndrome was much higher if one develops COVID-19 infection (i.e., has a positive COVID test) than after receiving the Astra Zeneca vaccine. The general sense is that there are COVID-19 vaccines that are safe in individuals whose Guillain-Barré syndrome was not associated with a previous vaccination and that actual infection is the greater risk for developing Guillain-Barré Syndrome. 

The U.S. Centers for Disease Control and Prevention (CDC) site offers information on vaccine resources. The National Institutes of Health (NIH) has information on vaccines for the coronavirus. The CDC  has make public its report on the association of Guillain-Barré Syndrome with the Janssen COVID-19 Vaccine and no increased incidence occurred after vaccination with the Moderna or Pfizer vaccines.

More information about Guillain-Barré Syndrome here.

There have been reports of  neurological complications from other SARS-CoV-2 vaccinations. Visit the FDA COVID-19 Vaccines webpage for information about coronavirus vaccines and fact sheets for recipients and caregivers that outline possible neurological and other risks.

Peripheral facial nerve palsy associated with COVID-19

Journal of NeuroVirology volume 26, pages941–944 (2020)Cite this article

Authors: Marco A. LimaMarcus Tulius T. SilvaCristiane N. SoaresRenanCoutinhoHenrique S. OliveiraLivia AfonsoOtávio EspíndolaAna Claudia Leite & Abelardo Araujo 

Abstract

COVID-19 pandemic revealed several neurological syndromes related to this infection. We describe the clinical, laboratory, and radiological features of eight patients with COVID-19 who developed peripheral facial palsy during infection. In three patients, facial palsy was the first symptom. Nerve damage resulted in mild dysfunction in five patients and moderate in three. SARS-Cov-2 was not detected in CSF by PCR in any of the samples. Seven out of eight patients were treated with steroids and all patients have complete or partial recovery of the symptoms. Peripheral facial palsy should be added to the spectrum of neurological manifestations associated with COVID-19.

Introduction

The ongoing COVID-19 pandemic has affected millions of people worldwide and revealed several neurological syndromes related to this infection. Anosmia/ageusia, encephalitis, encephalopathy, cerebrovascular complications, myelitis, and Guillain-Barré syndrome, among other neurological complications, occur in a significant proportion of patients (Ellul et al. 2020; Paterson et al. 2020).

Acute facial nerve palsy commonly occurs in clinical practice and is associated with considerable distress due to possible functional and esthetic sequelae (Jowett 2018). There are many potential mechanisms implicated in its occurrence, including viral infections. Herein, we review the clinical and laboratory features of eight patients with COVID-19 who developed peripheral facial palsy during the clinical course of the infection or as its first symptom.

Methods

Case series of eight patients seen from May to July 2020 with a diagnosis of COVID-19 based on positive SARS-CoV-2 RNA RT-qPCR in nasal and oropharyngeal swabs (Biomanguinhos kit (E+P1), FIOCRUZ, Brazil).

Data about the onset of facial palsy, associated clinical conditions, brain imaging, cerebrospinal fluid parameters, treatment, and outcome were recorded. Facial palsy was graded according to the House-Brackmann scale (House and Brackmann 1985). This study was approved by the Local Ethical Committee at INI/FIOCRUZ.

Results

Among the eight patients, seven were women. All had COVID-19 diagnosis based on positive SARS-CoV-2 RNA RT-qPCR in nasal and oropharyngeal swabs. The mean age was 36 years (range 25–50 years). In three patients, facial palsy was the first symptom of COVID-19, while in the remaining five, it appeared from 2 to 10 days after onset of other clinical manifestations. All patients had mild respiratory and systemic COVID-19 symptoms, and none required hospitalization. According to the House-Brackmann grading system, nerve damage resulted in mild (grade 2) dysfunction in five patients and moderate (grade 3) in three (Table 1). The neurological examination disclosed no abnormalities in all but one patient, who had an associated ipsilateral abducent nerve palsy. Deep tendon reflexes were preserved, and no sensory abnormalities were present. Six patients underwent lumbar puncture with normal opening pressure in all cases. CSF analysis showed no inflammatory changes except for a mild protein elevation in one patient (50 mg/dl) (Table 1). SARS-Cov-2 was not detected in CSF by PCR in any of the samples. Imaging (CT scan or MRI) was normal in seven patients. In one patient, MRI showed contrast enhancement in the distal intracanalicular portion in the tympanic and mastoid segments of the left facial nerve (Fig. 1).Table 1 Clinical and laboratory manifestations of COVID-19 patients with facial palsy

Full size table

figure 1
Fig. 1

Six out of seven patients were treated with oral steroids (prednisone 40–60 mg/day for 5–7 days) and one received intravenous methylprednisolone. One patient with mild manifestations received only supportive care (eye lubricant) with complete recovery 2 days later. Two patients received oral acyclovir concomitant to steroids due to possible Herpes simplex virus infection. Complete recovery occurred in five patients, while the other three still had some degree of facial weakness at the last follow-up 30 days after onset of neurological symptoms.

Discussion

Infections such as HSV-1, VZV, and Lyme disease are common causes of facial paralysis (Owusu et al. 2018). The rapid expansion of COVID-19 pandemics led to the development of a growing number of neurological syndromes. Our study shows that peripheral facial palsy can occur during the clinical course of COVID-19 or anticipate other typical manifestations such as fever and respiratory symptoms.

Interestingly, all but one of our patients were women. Idiopathic facial palsy does not have a gender preference (Katusic et al. 1986). Indeed, our sample is too small to assume any conclusion, and the two other cases of isolated facial palsy in association with COVID-19 described by Goh and Casas were men (Casas et al. 2020; Goh et al. 2020).

Most patients in this study had isolated facial palsy with mild or moderate dysfunction and no other neurological findings. Except for the two described above by Goh and Casas (Casas et al. 2020; Goh et al. 2020), in all other studies, facial paralysis in COVID-19 patients occurred unilaterally or bilaterally in association with other manifestations of Guillain-Barré syndrome (Manganotti et al. 2020; Ottaviani et al. 2020; Juliao Caamaño and Alonso Beato 2020; Paybast et al. 2020; Sancho-Saldaña et al. 2020; Bigaut et al. 2020).

CSF basic parameters (cellularity, protein, and glucose levels) are usually normal in patients with idiopathic facial paralysis as observed in our series (Bremell and Hagberg 2011). SARS-CoV2 was not detected in any five cases who underwent lumbar puncture, which is consistent with a recent study that failed to show viral RNA in the CSF of COVID-19 patients with different neurological syndromes (Espíndola et al. 2020).

Possible mechanisms related to nerve damage in idiopathic facial nerve paralysis include ischemia of vasa nervorum and demyelination induced by an inflammatory process (Zhang et al. 2020). Microthrombi and other vascular changes have been consistently reported in several postmortem studies (Silberzahn et al. 1988; Nunes Duarte-Neto et al. 2020) and may be implicated in the development of facial nerve ischemia in COVID-19 patients. Direct viral damage or an autoimmune reaction toward the nerve producing inflammation would be alternative or contributing mechanisms to dysfunction.

Supportive care and oral steroids are the mainstays of treatment (Sullivan et al. 2007). Our patients had complete recovery or significant improvement in few weeks after treatment as the patient reported by Casas et al. (2020), suggesting a good outcome when peripheral facial palsy occurs in association with COVID-19.

In conclusion, peripheral facial palsy should be added to the spectrum of neurological manifestations associated with COVID-19. Most patients had an uncomplicated course with good outcome, and SARS-CoV-2 RNA could not be detected in CSF of any patient.

References

Syncope and COVID-19 disease – A systematic review

Authors: Raquel Falcão de Freitas 1Sofia Cardoso Torres 2Francisco Javier Martín-Sánchez 3Adrián Valls Carbó 3Giuseppe Lauria 4José Pedro L Nunes

. 2021 Nov;235:102872. doi: 10.1016/j.autneu.2021.102872. Epub 2021 Aug 27.

Abstract

Background

Syncope is not a common manifestation of COVID-19, but it may occur in this context and it can be the presenting symptom in some cases. Different mechanisms may explain the pathophysiology behind COVID-19 related syncope. In this report, we aimed to examine the current frequency and etiology of syncope in COVID-19.

Methods

A systematic review across PubMed, ISI Web of Knowledge and SCOPUS was performed, according to PRISMA guidelines, in order to identify all relevant articles regarding both COVID-19 and syncope.

Results

We identified 136 publications, of which 99 were excluded. The frequency of syncope and pre-syncope across the selected studies was 4.2% (604/14,437). Unexplained syncope was the most common type (87.9% of the episodes), followed by reflex syncope (7.8% of the cases). Orthostatic hypotension was responsible for 2.2% of the cases and syncope of presumable cardiac cause also accounted for 2.2% of cases. Arterial hypertension was present in 52.0% of syncope patients. The use of angiotensin receptor blockers or angiotensin converting enzyme inhibitors were not associated with an increased incidence of syncope (chi-square test 1.07, p 0.30), unlike the use of beta-blockers (chi-square test 12.48, p < 0.01).

Conclusion

Syncope, although not considered a typical symptom of COVID-19, can be associated with it, particularly in early stages. Different causes of syncope were seen in this context. A reevaluation of blood pressure in patients with COVID-19 is suggested, including reassessment of antihypertensive therapy, especially in the case of beta-blockers rterial hypertension

1. Introduction

The ongoing Coronavirus pandemic has proved to be a challenging setback to the health of the world population ever since its first cases were announced in the city of Wuhan, China, around December 2019. As of the 1st of July 2021, there have been a total of approximately 181 million confirmed cases of COVID-19 (Coronavirus disease 2019) worldwide and 3.9 million deaths, translating to a fatality rate of 2% (

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel betacoronavirus and COVID-19 is the infectious disease caused by this novel virus. Its spike protein (glycoprotein S) determines the specificity of the virus for epithelial cells of the respiratory tract (. It is composed of a receptor binding domain that recognizes the ACE-2 (type 2 angiotensin converting enzyme) receptor specifically, allowing the entrance of the virus into its target cells (

Wang et al., 2020

). The ACE-2 receptor can be found on the surface of epithelial cells in the lungs, intestines, kidneys and blood vest is currently known that, although the novel SARS-CoV-2 virus can lead to significant disease in the respiratory system, it can also negatively affect several other vital organ systems. Significant damage, namely, to the cardiovascular, nervous and hematopoietic systems has been outlined and an impact in hemostasis has also been thoroughly discussed as blood hypercoagulability is common among hospitalized COVID-19 patient). Regarding the cardiovascular manifestations, heart failure, thromboembolism, myocarditis, arrhythmias, pericarditis and acute coronary syndromes have been described in this contex). On the other hand, the most common neurological symptoms reported in COVID-19 patients have been smell and taste disturbances, headache, myalgia, and altered mental status (yncope is largely defined as a transient loss of consciousness due to cerebral hypoperfusion

). It is characterized by a rapid onset, short duration and spontaneous, complete rec

). Presyncope, on the other hand, is the state that resembles the prodrome of syncope (with all its signs and symptoms such as pallor, sweating, nausea, palpitations) without being followed by a loss of consciousness (In the light of a severe systemic disease, non-traumatic transient loss of consciousness can have distinct etiologies, varying from the benign reflex syncope and syncope due to orthostatic hypotension to the increasingly serious cardiac). Apart from unexplained syncope, these three main groups stem from different mechanisms and, therefore, may require specialized treatment. Consequently, an accurate diagnosis becomes imperative.

Recently, some case reports and case-series have emerged reporting syncope as a possible symptom of COVID-19, whether it had developed at the onset or during the course of the d). It is important to mention that some of these reports outline its occurrence days before the main respiratory symptoms, or even as an isolated p). If a valid relationship between COVID-19 and syncope is established, a number of patients could be isolated in a timely manner, minimizing the contagious phase.

In the present report, we aimed to systematically review the recent published literature that describes syncope or presyncope as a symptom of COVID-19, having it been observed in the days before or after the diagnosis. We aimed to calculate its frequency and divide it into each different type of syncope observed.

As a secondary aim of the review, the investigation of the relationship between syncope and use of angiotensin receptor inhibitor drugs (ACEi), angiotensin receptor blockers (ARBs) and/or beta-blockers in the context of COVID-19 was carried out. This seemed to be important to investigate since arterial hypertension is a common comorbidity among COVID-19 patien, and the use of standard anti-hypertensive agents could influence the incidence of this symptom.

2. Methods

2.1 Eligibility criteria

Regarding our population of interest, we were in the search for studies that simultaneously described COVID-19 and syncope or presyncope presented as a possible symptom of the acute infection or occuring in a post-acute COVID-19 setting. Articles were excluded if they described falls in the context of COVID-19 that were not stated to be of syncopal origin; episodes of syncope not temporally related with SARS-CoV-2 infection (for example, occurring throughout the year prior to the infection) and episodes of syncope with another possible underlying cause mentioned in the study as relevant apart from COVID-19. We included case-series, case-reports, cross-sectional studies with prospective data collection, retrospective analyses and letters published in 2020 or 2021 for which it was possible to extract an exact number of patients with COVID-19 exhibiting syncope/presyncope.

We did not restrict articles to witnessed syncope nor exclude articles that did not describe the specific comorbidities, clinical characteristics or evolution exhibited by the pre/syncope cohort. This was because our primary outcome measure was to quantify the number of COVID-19 related pre/syncopal episodes published in the literature thus far.

We considered articles written in English, Spanish, French, Italian, or Portuguese. Articles written in German, Hungarian or Mandarin were excluded (since the authors are not familiar with these languages).

2.2 Search strategy

A comprehensive literature search was carried out with the purpose of identifying all reported articles relating syncope to COVID-19, according to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analys. This search was conducted on the databases Medline (PUBMED), ISI Web of Knowledge and SCOPUS.

The search query, which took place on the 9th of March 2021, included the following MeSH terms and keywords: “(“COVID-19” OR “COVID 19” OR “SARS-COV-2” OR “coronavirus” OR “2019 novel coronavirus”) AND (“syncope” OR “presyncope” OR “syncopal”). Additionally, we scanned the list of references from the included studies in this analysis and of systematic reviews pertaining to neurological symptoms in the context of COVID-19.

2.3 Selection process

Two investigators independently assessed whether the studies addressed the topic in question and if all the inclusion/exclusion criteria were met. Initially, this was done according to the “screening phase”, where only the title and the abstract were analyzed. After this process, 52 articles were considered eligible. This was followed by the “inclusion phase”, where the integral text was fully evaluated. Any doubtful situation was solved by consensus between the authors, after which, concerning study eligibility, 100% agreement between authors was seen in each step of the study assessment.

2.4 Data collection process and data items

From the selected articles, two authors worked independently to retrieve the following data: location, number of patients (with and without pre/syncope), age, sex and ethnicity when available, comorbidities (from patients with and without pre/syncope), chronic medications the patients were on regarding treatment of arterial hypertension and the description of the clinical course, including relevant laboratory findings and any auxiliary exams performed, such as computerized tomography scans and cardiac magnetic resonances. Any doubtful situation was solved by consensus between the authors.

2.5 Study quality assessment

Quality of the observational cohorts and cross-sectional studies and case-series was evaluated using the National Heart, Lung and Blood Institute study quality assessment t

) and is presented in Table 1Table 2. Any disagreements between the two main reviewers were discussed with a third evaluator.

Table 1Quality assessment tool for observational cohort and cross-sectional studies. Y – Yes; NR – Not Reported; NA – Not Applicable.

Oates et al.Chen et al.Canetta et al.Radmanesh et al.Chachkhiani et al.García-Moncó et al.Xiong et al.Romero-Sánchez et al.Chuang et al.Mizrahi et alMartin-Sanchez et al.Travi et al.Chou et al.
Was the research question or OBJECTIVE in this paper clearly stated?YYYYYYYYYYYYY
Was the study population clearly specified and defined?YYYYYYYYYYYYY
Was the participation rate of eligible persons at least 50%?YYYYYYYYYYYYY
Were all the subjects selected or recruited from the same or similar populations (including the same time period)? Were inclusion and exclusion criteria for being in the study prespecified and applied uniformly to all participants?YYYYYYYYYYYYY
Was a sample size justification, power description, or variance and effect estimates provided?NRNRNRNRNRNRNRNRNRNRNRNRNR
For the analyses in this paper, were the exposure(s) of interest measured prior to the outcome(s) being measured?NANANANANANANANANANANANANA
Was the timeframe sufficient so that one could reasonably expect to see an association between exposure and outcome if it existed?YYYYYYYYYYYYY
For exposures that can vary in amount or level, did the study examine different levels of the exposure as related to the outcome (e.g., categories of exposure, or exposure measured as continuous variable)?NANANANANANANANANANANANANA
Were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants?YYYYYYYYYYYYY
Was the exposure(s) assessed more than once over time?NRNRNRNRNRNRNRNRNRYYNRNR
Were the outcome measures (dependent variables) clearly defined, valid, reliable, and implemented consistently across all study participants?YYYYYYYYYYYYY
Were the outcome assessors blinded to the exposure status of participants?NANANANANANANANANANANANANA
Was loss to follow-up after baseline 20% or less?NRNRNRNRNRNRNRNRNRNRNRNRNR
Were key potential confounding variables measured and adjusted statistically for their impact on the relationship between exposure(s) and outcome(s)?NRNRNRNRYNRNRNRNRYYYY
Quality ratingGoodFairGoodGoodGoodFairFairFairFairGoodGoodGoodGood

Table 2Quality assessment tool for case-series studies. Y – Yes; NR – Not reported; NA – Not applicable.

Ebrille et al.Birlutiu et al.Argenziano et al.Espinoza et al.Gonfiotti et al.
Was the study question or objective clearly stated?YYYYY
Was the study population clearly and fully described, including a case definition?YYYYY
Were the cases consecutive?NRNRYNRNR
Were the subjects comparable?YYYYY
Was the intervention clearly described?YYYYY
Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants?YYYYY
Was the length of follow-up adequate?NRYYNRY
Were the statistical methods well-described?NANAYNANA
Were the results well-described?YYYYY
Quality RatingFairGoodGoodFairGood

2.6 Outcome measures

The primary outcome measures assessed were the occurrence of syncope or presyncope either in the days prior or subsequent to a COVID-19 diagnosis and its relative frequency, divided into each type of syncope experienced.

We also assessed the association between the usage of ARBs or ACEi and beta blockers with the occurence of syncope as well as the association of syncope with mortality.

2.7 Effect measures

Concerning these latter data, a chi-square test was used, with a level of significance of 0.05. Statistical analysis was done using Stata, version 17.0, StataCorp, Texas, USA.

3. Results

3.1 Study selection

With the use of our keywords, we obtained 51 results from Medline (PUBMED), 28 from ISI Web of Knowledge, 50 from SCOPUS and 7 from scanning the references of the selected articles and adequate systematic reviews (Fig. 1) – with a total number of 37 articles selected for the purpose of the present study (Fig. 1). The complete set of selected studies is presented in Table 3. SARS-CoV-2 infection was diagnosed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or a chest X-ray or CT scan showing the characteristic bilateral interstitial pneumonia of COVID-19 in all cases, except in the report by Romero-Sánchez et al., in which a minority of patients were diagnosed by means of serological testing

Fig. 1
Fig. 1Flowchart showing literature search method. n = number of articles.View Large ImageDownload Hi-res imageDownload (PPT)

Table 3Summary of included articles. Pts – patients; ARBs – angiotensin receptor blockers; PPM – permanent pacemaker implantation; ECG – electrocardiogram; ICD – implantable cardioverter-defibrillator; AV – atrioventricular; ACE-I – angiotensin-converting-enzyme inhibitors; CMR – cardiac magnetic resonance; CSF – cerebrospinal fluid; CT -computed tomography; MRI – magnetic resonance imaging; RT-PCR – real time polymerase chain reaction; CRP – C-Reactive Protein, NT-proBNP – N-terminal type B natriuretic peptide; POTS – Postural Orthostatic Tachycardia Syndrome; BP – blood pressure. 

Post-COVID ‘brain fog’ could be result of virus changing patients’ spinal fluid

Authors: by John Andere JANUARY 19, 2022

Cases of “brain fog” among COVID patients are becoming more and more common, even among people recovering from mild infections. Now, new research is finally providing some potential answers to why people have difficulty concentrating, thinking clearly, and completing easy daily tasks after battling COVID. A team from the University of California-San Francisco say brain fog may result from how the virus alters a person’s spinal fluid — just like other diseases which attack the brain.

Their study finds certain patients who develop cognitive symptoms following a mild case of COVID-19 display abnormalities in their cerebrospinal fluid, similar to the kinds which appear in patients with diseases like Alzheimer’s. While this is only a start, study authors are optimistic this work is an important first step toward understanding what exactly SARS-CoV-2 can do to the human brain.

“They manifest as problems remembering recent events, coming up with names or words, staying focused, and issues with holding onto and manipulating information, as well as slowed processing speed,” explains senior study author Joanna Hellmuth, MD, MHS, of the UCSF Memory and Aging Center, in a university release.

Post-COVID brain fog is likely much more common than most people realize. One recently released study focusing on a post-COVID clinic in New York found that a staggering 67 percent of 156 recovered COVID-19 patients experienced some form of brain fog.

Brain fog patients experience more brain inflammation

This latest research featured 32 adults. All participants had recovered from a COVID-19 infection but did not require hospitalization. Twenty-two exhibited genuine cognitive symptoms, while the rest served as a healthy control group.

Among the entire group, 17 (including 13 with brain fog symptoms) agreed to have their cerebrospinal fluid analyzed. Scientists extracted the fluids from the lower back, on average, about 10 months after each patient’s first COVID symptoms.

Those tests showed 10 of the 13 participants with cognitive symptoms had anomalies within their cerebrospinal fluid. Importantly, the other four cerebrospinal fluid samples collected from people without brain fog showed no anomalies whatsoever. Participants experiencing cognitive issues tended to be older, with an average age of 48, while the control group’s average age was younger: 39 years-old.

All of the patients come from the Long-term Impact of Infection with Novel Coronavirus (LIINC) study, which tracks and assesses adults recovering from SARS-CoV-2.

Further analyses performed on the cerebrospinal fluid samples showed higher-than-normal protein levels and the presence of some unexpected antibodies usually found in an activated immune system. Researchers say these observations suggest a high level of inflammation. Some of these antibodies were seen in the blood and cerebrospinal fluid, implying a systemic inflammatory response. Some antibodies, however, were unique to the cerebrospinal fluid, which hints at brain inflammation specifically.

Study authors don’t know the intended target of these antibodies yet, but theorize they may attack the body itself, like an autoimmune disease.

“It’s possible that the immune system, stimulated by the virus, may be functioning in an unintended pathological way,” explains Dr. Hellmuth, who is the principal investigator of the UCSF Coronavirus Neurocognitive Study. “This would be the case even though the individuals did not have the virus in their bodies.”

Pre-existing conditions raise the risk of COVID brain fog

Notably, patients dealing with brain fog symptoms had an average of 2.5 cognitive risk factors, such as diabetes, high blood pressure, or a history of ADHD, in comparison to an average of less than one average risk factor for participants without brain fog symptoms.

These cognitive risk factors are relevant because they potentially raise an individual’s risk of stroke, mild cognitive impairment, vascular dementia, and generally make the mind more susceptible to executive functioning issues. Additional risk factors include drug use, learning disabilities, anxiety, and depression.

Additionally, all participants underwent a series of cognitive tests with a neuropsychologist modeled after the criteria used for HIV-associated neurocognitive disorder (HAND). To the research team’s surprise, 59 percent of patients dealing with brain fog met HAND criteria, while 70 percent of the control subjects did the same.

“Comparing cognitive performance to normative references may not identify true changes, particularly in those with a high pre-COVID baseline, who may have experienced a notable drop but still fall within normal limits,” Dr. Hellmuth concludes. “If people tell us they have new thinking and memory issues, I think we should believe them rather than require that they meet certain severity criteria.”

The study is published in the journal Annals of Clinical and Translational Neurology.