Auditory Disturbances and SARS-CoV-2 Infection: Brain Inflammation or Cochlear Affection? Systematic Review and Discussion of Potential Pathogenesis

Pietro De Luca1Alfonso Scarpa1Massimo Ralli2Domenico Tassone3Matteo Simone3Luca De Campora3Claudia Cassandro4† and Arianna Di Stadio Frontiers in Medicine

Patients affected by COVID-19 present a series of different symptoms; despite some of these are common, other less likely appear. Auditory symptoms seem to be less frequent, maybe because rarer or, alternatively, because they are underestimated during the clinical investigation. The hearing impairment might be related to the central or peripheral involvement of the auditory pathways; in particular, the likelihood of thrombosis might be one of the causes. To date, the prevalence of auditory symptoms such as sudden or progressive sensorineural hearing loss and tinnitus is unclear in COVID-19 patients. However, their presence might be an early sign of thrombosis or spread of the infection into the brain. In this systematic review of the literature we investigated the presence of auditory symptoms in COVID-19 patients and discussed their potential origin and causal relationship with SARS-CoV-2. Results showed that, despite rarely, auditory impairment can appear in patients with COVID-19 and should always be investigated for an early treatment and potential indicator of involvement of the central nervous system.

Introduction

Coronavirus Disease 19 (COVID-19) has spread worldwide, negatively impacting the healthcare systems and institutions (1). COVID-19 presents several symptoms, that generally arise 2-14 days after the start of the infection. Common symptoms include fever, cough, shortness of breath, respiratory distress; furthermore, olfactory and gustatory alterations have been widely reported (23). The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is responsible of different neurological manifestations and systemic complication (4).

Despite rarely, several viral infections that determine inflammation of the cochlea can cause auditory deficits (5); the pathogenetic mechanisms of these symptoms have been widely explained and confirmed by the literature (67). Researchers have attributed their onset to the peripheral damage affecting the cochlea (6) or to the involvement of the central auditory pathways (8).

Several studies have described the presence of brain lesions as responsible of auditory impairment (911), supporting the hypothesis that SARS-CoV-2, which has neuro-invasive characteristics, might determine a central hearing loss in COVID-19 patients both in the active phase and during recovery (12). It has been shown that the virus can spread from neuroepithelium to the olfactory bulb to the brain (1315), causing loss of smell (16), persistent cough after pneumonia resolution (17), memory deficit (18), and neurocognitive problems (19).

Although the central hypothesis seems to be the most plausible, the peripheral involvement of the cochlea cannot be totally excluded.

The presence of auditory symptoms in COVID-19 might be underestimated because they are not a primary symptom of the disease, while they might be a sign of the spread of the virus in the superior auditory pathways, or of a thrombosis.

The aim of this paper is to assess the incidence of sudden sensorineural hearing loss (SSNHL) and hearing deterioration in COVID-19 patients and discuss their possible causes.

Methods

This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist and statement recommendations (Figure 1). The nature of this review did not require Institutional Review Board approval.

Figure 1

FIGURE 1. Prisma diagram to illustrate the method used to select the articles.

Search Strategy

A comprehensive search strategy, developed in partnership with a medical librarian, was performed on PubMed, Scopus and Google Scholar without time restrictions. The keywords used were: “hearing loss,” “hearing impairment” “tinnitus” “audio and vestibular symptom” “sudden hearing loss,” “SARS-CoV-2” and “COVID-19”. Only articles in the English language were considered for the analysis.

Two independent investigators reviewed the articles extracted from the literature review. Duplicates were removed, then each reviewer singularly filled in an Excel data sheet (Microsoft Corporation, USA) including information extracted from the articles. Files were then compared and disagreements on the inclusion/exclusion papers were debated until complete agreement of both researchers. Only papers that received full consensus were considered.

PRISMA guidelines were followed to conduct the systematic review and the full list of references was screened for potentially relevant articles.

Study Selection Criteria

We included articles with the following characteristics: patients (0-99 years) affected by sudden sensorineural hearing loss or hearing deterioration after SARS-CoV-2 infection, written in English language, with full-text available. There were no restrictions in terms of diagnostic tools used to detect SARS-CoV-2. Suspected/unconfirmed COVID-19 patients were excluded. Selected articles were read in full to assess the study objectives and the level of evidence.

Data Extraction

A spreadsheet was filled using the data extracted from the articles read in full by the researchers. The following information were included: name of the author, year of publication, type of study, country where the study was conducted, number of subjects analyzed, patients’ characteristics, auditory results, treatment, outcome, presence or absence of the comparison group, characteristics of control groups.

Risk of Bias Assessment

The National Institutes of Health’s (NIH) quality assessment tools were used to assess the risk-of-bias checklists due to the different study designs (20). The rating of each study was categorized as: poor, fair or good (i.e., unbiased and fully described). The two authors independently gave a score to each article and any disagreement was resolved by direct comparison among the researchers.

Results

Study Selection

One-hundred seventeen records were identified (Figure 1 and Table 1). After removal of duplicates and abstract evaluation, 93 articles were excluded. Twenty-four full-text articles matched the inclusion/exclusion criteria. Five full-text articles were excluded because at high-risk of bias and the remaining 19 were included in the systematic review. The articles identified an association between SARS-CoV-2 and hearing impairment/sudden sensorineural hearing loss. All studies were published over a period of 2 years, between 2019 and 2021.

Table 1

TABLE 1. Summary of studies included in the systematic review.

Study Characteristics

Sudden Sensorineural Hearing Loss in Patients With SARS-CoV-2 Infection

Twelve full-text articles were identified (72131) (Table 2); we identified 11 case reports and 1 case series. Two studies were conducted in Turkey, two in France, two in the United Kingdom, and one in each of the following countries: Thailand, Germany, Brazil, Australia, Egypt, and United States of America. Sixteen patients (10 men and 6 women; age range 18-84 years) evaluated in these studies tested positive for COVID-19. All patients suffered from SSNHL; tinnitus was reported by four patients. Two patients suffered from vertigo, two had nausea or vomiting, and one was affected by ear fullness. Four subjects had bilateral impairment. Five patients had right SSNHL and five left SSNHL; in two studies the side of the affection was not specified. The hearing function was always (100%) assessed by pure tone audiometry (PTA); tympanometry was performed in three studies, speech audiometry and otoacoustic emissions in one, respectively. Two studies did not report the audiological assessment.

Table 2

TABLE 2. Characteristics of studies exploring sudden sensorineural hearing loss (SSNHL) in patients with COVID-19 and included in the systematic review.

Nine patients were exclusively treated by oral steroids, one subject with intratympanic steroid only; three patients were treated by combining oral steroid and intratympanic corticosteroids. In one case the treatment was not described. One patient, who did not recover, needed cochlear implant and only one patient recovered spontaneously.

Three patients completely recovered the auditory function (only one spontaneously) and five had a partial improvement; two studies did not mention the hearing outcome.

Hearing Loss in Patients With SARS-CoV-2 Infection

Seven full-text articles were identified (27323638) (Table 3). They included four prospective studies, one retrospective study, one case series, and one case report. The studies were conducted in Italy, Portugal, Iran, United Kingdom, Turkey, Egypt, and Qatar. A total of one 188 patients were evaluated. Ninety-three patients were males, 95 were females; age ranged from 0 to 82 years. Only one study did not report details about age and gender of the patients. Hearing ability was assessed by PTA by four authors, speech audiometry in one study, otoacoustic emissions in three and tympanometry in two articles. Only one author reported hearing capacity as “self-reported hearing loss” without objective assessment.

Table 3

TABLE 3. Characteristics of studies exploring hearing loss (HL) in patients with COVID-19 included in the systematic review.

Discussion

The results of our systematic review showed that, despite uncommon, the hearing function might be affected by SARS-CoV-2 infection. Because of wide differences among the studies and the lack of clinical trials, we were not able to perform a meta-analysis to clarify the real prevalence of this symptom.

Gallus et al. (32) performed a retrospective study investigating the audiological and vestibular characteristics of 48 non-hospitalized patients affected by COVID-19; after two consecutive negative RT-PCR on nasopharyngeal swabs, the doctors analyzed patients’ auditory and vestibular functions. All subjects were investigated by pure-tone audiometry, tympanometry, and cochleo-stapedius reflex. Four (8.3%) of them reported self-perception of hearing loss, in presence of normal hearing threshold at the time of testing.

Alves de Sousa et al. (33) in a prospective study showed that patients with light forms of COVID-19 had worse auditory thresholds at 1,000, 2,000, 4,000, and 8,000 Hz compared to healthy subjects, and the severity of hearing loss worsened in patients with moderate-severe forms of the disease. The results observed by Karimi-Galougahi et al. (34) and the report from Chirakkal et al. (38) confirmed the association between hearing deterioration and SARS-CoV-2 infection in a sample of five patients.

Celik et al. tested the auditory function on newborns from mothers who suffered from COVID-19 during pregnancy; 37 infants were studied by transient evoked otoacoustic emission (TEOAEs), distortion product otoacoustic emission (DPOAE), and contralateral suppression of otoacoustic emission (CLS OAE). The results were compared to healthy controls. The authors found statistically significant differences between TEOAEs (3,000 and 4,000 Hz) of infants exposed to COVID-19 infection during pregnancy compared to the ones of non-exposed newborns. Analyzing the results of CLS OAE, the authors observed similar significant statistical differences in all auditory frequencies (more significant at high frequencies) (35). Mustafa et al. used TEOAE to evaluate the hearing function in a cohort of asymptomatic COVID-19 patients; their results were compared to those of non-infected subjects. The authors identified that TEOAE amplitude was significant worse in SARS-CoV-2 positive subjects compared to the control (36). Munro et al. investigated the hearing functions of 138 adult patients with confirmed SARS-CoV-2 infection using a questionnaire; 16 (13.2%) patients referred changes in their hearing status after COVID-19 diagnosis; unfortunately, no audiological evaluation was performed to objectively assess the hearing in this cohort (37).

Sriwijtalaia and Wiwanitkit were the first to describe a correlation between COVID-19 and hearing loss (21); unfortunately, detailed data about patients’ characteristic were missing. Similarly, Degen et al. (22) described a 60-year-old man with profound SSNHL and COVID-19, but they did not report the outcome after treatment. Lang et al. (23) described a 30-year-old woman with severe unilateral SSNHL treated with oral steroids without significative improvement of the symptom. Furthermore, Lamounier et al. (24) and Koumpa et al. (25) showed that patients (one case for each author) could obtain partial recovery of their hearing function combining oral and intratympanic steroids. Guigou et al. described a 29-year-old man with bilateral SSNHL and positive to SARS-CoV-2, who obtained complete recovery of the hearing after treatment with oral corticosteroids (26). Notably, in this patient the SSNHL was the presenting symptom of COVID-19.

Chern et al. showed a case of bilateral intralabyrinthine hemorrhage in an adult woman affected by COVID-19; the patient suffered from bilateral SSNHL, aural fullness and vertigo. The magnetic resonance imaging (MRI) showed bilateral intralabyrinthine hemorrhage, which was identified as the cause of the hearing symptoms. The patient partially recovered hearing function after treatment with high-dose oral prednisone and left intratympanic dexamethasone injection (31).

Perret et al. described a case of acute labyrinthitis and SSNHL (29); the patient was treated with oral prednisone and showed progressive recovery. The oral steroid treatment was effective also for treating the hearing impairment in a patient on peritoneal dialysis program who showed SSNHL as presenting symptom of SARS-CoV-2 infection (29). An improvement of the hearing capacity was also reported by Abdel Rhman and Abdel Wahid (30); in this case the patient was treated with intratympanic steroids.

Kilic et al., speculating that hearing loss could be a presenting symptom of COVID-19, performed a real-time polymerase chain reaction (RT-PCR) in five consecutive male patients presenting with unilateral SSNHL. Only one of these subjects was positive for SARS-CoV-2, and SSNHL positively responded to COVID-19-specific treatment in the SARS-CoV-2 (739).

Finally, Jacob et al. observed a complete and spontaneous recovery of hearing in a 61-year-old woman with SSNHL and SARS-CoV-2 infection (27).

Etiopathology of Hearing Impairment in COVID-19

In patients affected by COVID-19, hearing loss and hearing disturbances might be related to a central and/or peripheral involvement of the auditory pathways. The cause can be indirectly (e.g., thrombosis) or directly (e.g., viral spread) related to SARS-CoV2.

SARS-CoV-2 infection increases the risk of systemic thrombosis (40), a condition that may determine neurological symptoms (41). Thrombosis is more common in the mild/moderate forms of the disease (42) rather than in severe ones, probably because in the latter anti-coagulant therapy is promptly administered (4243). An alteration of coagulation rate (44) could cause a macro and/or micro thrombosis, with consequent transitory ischemia and hypoxia in the auditory pathways determining the onset of hearing alterations. The thrombus, which can occlude the cochlear-vestibular artery or one of its afferent vessels (Figure 2), could determine transitory SSNHL or, in case of extremely rapid resolution, a slight hearing impairment or tinnitus. However, despite rapid resolution, transitory hypoxia into the cochlea could stress the inner ear cells and increase the concentration of reactive oxygen species (ROS), that could be responsible of additional damage of the hair cells. On the other hand, a thrombus in one of the vessels of the superior auditory pathways (Figure 2) can determine central hearing loss (45).

Figure 2

FIGURE 2. Direct Virus Effect. The image clearly shows the contiguity between the olfactory and the auditory areas. The virus can easy spread from the olfactory bulb to the olfactory area, reach the auditory area and once there inducing neuroinflammation responsible of the onset of the auditory symptoms.

Another hypothesis is that central auditory pathways—especially the auditory cortex (Figure 3)—might undergo the same inflammatory process observed in the olfactory area (16), directly caused by SARS-CoV-2. Recently, it has been confirmed that SARS-CoV2 spreads up to the olfactory bulb passing through the olfactory epithelium and lamina cribrosa (13); we speculate that the virus might, for contingency among the olfactory and auditory areas (Figure 3), determine transitory neuro-inflammation and consequent hearing symptoms. This hypothesis, although only speculative, could be supported by the clinical evidence of symptoms’ resolution using steroids.

Figure 3

FIGURE 3. Indirect Virus Effect. The images illustrates the different position of a potential trombosis, which can determine the onset of the audio-vestibular disorders because it stops the blood flow in the audiovestibular artery.

Moreover, the presence of vertigo/dizziness (4647) in patients with COVID-19 could have the same etiopathogenesis; in fact, a thrombosis in the audio-vestibular artery may alter the blood flow both in the cochlea and the vestibule explaining the presence of these symptoms (47). However, because of vestibular compensative mechanism, equilibrium disorders may be less perceived by the patients than hearing disturbances.

Vestibular disorders arising from central origin have been already confirmed in other diseases (4849); it is reasonable that SARS-CoV-2 spreading in the vestibular pathways may be responsible of equilibrium disorders observed in COVID-19 patients.

Limits of the Study

This study presents several limitations. First, the sample size (204 patients) is small. Second, the quality rating of the studies is not always satisfactory; in fact, there are several case reports and the cross-sectional studies have uncontrolled designs or provide insufficient details on the control groups. Third, in some studies the hearing deterioration could be already present before SARS-CoV-2 infection. Lastly, some of these studies described “self-reported symptoms” without an objective assessment of the hearing.

Conclusions

Hearing loss, despite rarely, might be present in COVID-19 patients. Auditory evaluation, although with all preventive measures to prevent contagion for healthcare providers, should be performed, especially if hearing disturbance are self-reported. The early recognition of these non-specific symptoms, which might be an early sign of brain inflammation, could help in preventing the spread of the infection to other areas of the brain.

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.

COVID fog demystified

Authors: Jennifer Kao 1Paul W Frankland 2PMID: 35768007PMCID: PMC9197953DOI: 10.1016/j.cell.2022.06.020

Abstract

Acute mild respiratory SARS-CoV-2 infection can lead to a more chronic cognitive syndrome known as “COVID fog.” New findings from Fernández-Castañeda et al. reveal how glial dysregulation and consequent neural circuit dysfunction may contribute to cognitive impairments in long COVID.

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Main text

More than 2 years since the first detected cases of COVID-19, the virus continues to evolve new variants, infect hundreds of millions of people, and pose both acute and chronic threats to global health. In most infections, a patient’s symptoms resolve within 2 weeks. However, recovery from initial infection is not always straightforward. In a significant fraction of patients, symptoms can persist for several months. This syndrome, which has become known as “long COVID,” may occur even following initially mild cases (that is, those not requiring hospitalization) and can include significant cognitive dysfunction.

Initial awareness of long COVID emerged from anecdotal accounts, shared by patients on social media platforms such as Twitter, Facebook, and Slack (Callard and Perego, 2021). Since then, a large number of studies have used more formal methods to catalog the nature and frequency of long COVID symptoms. Within the cognitive domain, as many as one in four patients experience a range of symptoms that have become known colloquially as “COVID fog,” which includes problems in attention, language fluency, processing speed, executive function, and memory (Becker et al., 2021).

Given the sheer scale of infections, there is a pressing need to understand how cognitive dysfunction emerges in long COVID. In this issue of Cell, a new paper by Fernández-Castañeda and colleagues (Fernández-Castañeda et al., 2022Geraghty et al., 2019) begins to address this need. Using mice as a model, they expressed human ACE2, the viral entry receptor required for successful COVID infection. Because ACE2 expression was restricted to the trachea and lungs, these mice developed only a mild form of the disease that was limited to the respiratory system and largely cleared within a week following intranasal inoculation with SARS-CoV-2 virus.

As a starting point, the researchers noted the striking similarities between COVID fog and another cognitive syndrome known as “chemobrain.” Chemobrain (or cancer-therapy-related cognitive impairment, CRCI), is a neuroinflammatory condition that patients often experience following radiation or chemotherapy. In CRCI, elevations in neurotoxic cytokines and reactive microglia (brain-resident macrophages) lead to cascades of multicellular events that impact forms of both gray and white matter plasticity that are important for healthy cognition (Gibson and Monje, 2021).

Adopting this framework, the authors quantified changes in cytokines and microglial/macrophage reactivity following SARS-CoV-2 infection. Reminiscent of CRCI, they found that microglial/macrophage reactivity was elevated in subcortical and hippocampal white matter in mice following mild respiratory COVID. Remarkably, this elevation was persistent and still evident even 7 weeks post infection. Outside of the brain, they detected elevated cytokine levels in the cerebrospinal fluid and serum of mice. Although levels of many cytokines were altered, one in particular grabbed their attention. CCL11 remained persistently elevated in mouse cerebrospinal fluid 7 weeks post infection. Notably, elevated CCL11 levels have been causally linked to cognitive impairments observed in normal aging (Villeda et al., 2011).

Similar patterns were found in patients with COVID-19 (Figure 1 ). Reactive microglia were elevated in subcortical white matter in individuals with COVID-19 (these patients were symptomatic for COVID-19 but died from other causes). Moreover, CCL11 was elevated in plasma from patients with long COVID. Remarkably, elevated CCL11 plasma levels were only detected in those long COVID patients with cognitive symptoms. CCL11 plasma levels were unaltered in long COVID patients who did not have cognitive symptoms. These findings suggest that CCL11 plays a central role in the brain pathology contributing to COVID fog.

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Figure 1

The neuroinflammatory basis of COVID fog

Acute mild respiratory COVID-19 infection can lead to a more chronic cognitive syndrome known as brain fog. Suggested pathways for brain fog include cytokine-induced activation of regional microglia, causing decreased hippocampal neurogenesis and a loss of myelinated subcortical axons.

There are several ways in which such a neuroinflammatory state might impact cognition. Previous work has shown that persistently reactive microglia in hippocampal white matter suppress hippocampal neurogenesis by blocking neuronal progenitor-cell differentiation into new granule cells (Monje et al., 2003). These newly generated neurons are important for the formation and stability of hippocampus-dependent memories. The authors found the numbers of new neurons were reduced in infected mice, and this reduction correlated with numbers of reactive microglia in the hippocampus. Remarkably, systemic administration of CCL11 recapitulated this same pattern in uninfected mice. Increased numbers of reactive microglia and decreased numbers of new neurons in these mice suggest a causal role for CCL11 in COVID fog pathology. These CCL11-induced outcomes were restricted to the hippocampus, suggesting that particular cytokines can have circuit-specific effects.

Another way in which CCL11 and/or reactive microglia might impact cognition is via effects on white matter. In CRCI, reactive microglia impair the formation of myelin-forming oligodendrocytes and myelin plasticity (Geraghty et al., 2019Gibson et al., 2019). Similarly, the authors found reduced numbers of oligodendrocytes and their precursor cells, as well as decreased axon myelination in the subcortical white matter, several weeks following infection in mice. Although behavior was not assessed in this study, it is nonetheless reasonable to assume that such changes would alter cognitive function following mild respiratory COVID in mice, as it does in other disease contexts (Geraghty et al., 2019Gibson et al., 2019). Since myelination regulates the speed and timing of communication between neurons, dysregulation of oligodendoglial lineage cells following infection might slow neural processing, disrupt brain synchrony, and impair cognition (Steadman et al., 2020).

The principle that inflammatory challenges may induce glial dysregulation and consequent neural circuit dysfunction is not specific to COVID-19. Many systemic infections are associated with lasting cognitive impairments. For instance, similar to COVID-19, the Spanish flu of 1918 (caused by H1N1 influenza virus infection) was associated with brain fog. In the current study, the authors compared the effects of mild respiratory SARS-CoV-2 infection with a mouse model of mild respiratory H1N1 influenza. Similar to SARS-CoV-2 infection, they found persistently elevated CCL11 in the H1N1 influenza infection. Therefore, CCL11-driven neuroinflammatory changes and cellular deficits may represent a common pathway to cognitive deficits in both mild respiratory COVID-19 and H1N1 influenza disease (as well as perhaps in other contexts, including aging).

However, different systemic infections can also have non-overlapping outcomes. For instance, whereas risk for anxiety and depression appears to be elevated in COVID-19, Spanish flu was associated with increased prevalence of psychosis (Honigsbaum, 2013). What accounts for these differences? One clue emerges from the current study. While CCL11 was elevated following SARS-CoV-2 and H1N1 influenza infection, a subset of cytokines was differentially regulated in these two conditions. It is likely that these non-overlapping cytokines (and their potentially non-overlapping circuit effects) might differentiate these diseases in terms of elevated risks for particular neuropsychiatric outcomes.

If cytokines have circuit-specific effects, should we consider cytokine profiling as a way to inform our treatment strategies for viral-induced/non-viral induced cognitive syndromes? Future research will no doubt address this and other outstanding questions. For instance, how are these effects mitigated by vaccination, administered before or after infection? And, perhaps most significantly, might interventions that block inducers of these cytokines or reset reactive microglia prove useful in treating COVID fog?

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Declaration of interests

The authors declare no competing interests.

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References

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How COVID-19 causes neurological damage found

Particularly in the group with the most serious neurological symptoms, the researchers identified a link with an excessive immune response.

Authors: PTI 15th November 2022 The Indian Express

COVID-19 may cause damage to the nervous system, even though it does not affect nerve cells, according to a small study.

While it was not uncommon for some people to lose their sense of taste and smell due to a Covid-19 infection, in others, the disease had had an even stronger impact on the nervous system, with effects ranging from lasting concentration problems to strokes, the study said.

Researchers, from the University of Basel and University Hospital Basel, Switzerland, have studied the mechanisms responsible for and reported new insights into the development of “neuro-Covid”, including identifying starting points for its prevention, the study said.

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, published in the journal Nature Communications, also indicate how to prevent neurological damage due to Covid-19.

The study included 40 Covid-19 patients with differing degrees of neurological symptoms.

n order to identify typical changes associated with neuro-Covid, the team of researchers compared cerebrospinal fluid and blood plasma of these individuals 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.

Particularly in the group with the most serious neurological symptoms, the researchers identified a link with an excessive immune response.

On the one hand, the study said, 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, the study said.

ALSO READ | Study: Blood tests might help to detect long covid in patients

“We suspect that these antibodies cross the porous blood-brain barrier into the brain, where they cause damage,” explained lead researcher Gregor Hutter.

Researchers also identified excessive activation of the immune cells specifically responsible for the brain — the microglia.

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.

ALSO READ | Covid virus ‘more likely than not, result of a research-related incident’: US report

The aim, the study said, 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.

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, the study said.

“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 said that the primary objective must be to identify and halt the excessive immune response at an early stage, the study said.ors

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. 

COVID-19 infections increase risk of long-term brain problems

Authors: Washington University in St. Louis Medical Xpress

COVID-19 infections increase risk of long-term brain problems
A comprehensive analysis of federal data by researchers at Washington University School of Medicine in St. Louis shows people who have had COVID-19 are at an elevated risk of developing neurological conditions within the first year after infection. Movement disorders, memory problems, strokes and seizures are among the complications. Credit: Sara Moser/Washington University School of Medicine

If you’ve had COVID-19, it may still be messing with your brain. Those who have been infected with the virus are at increased risk of developing a range of neurological conditions in the first year after the infection, new research shows. Such complications include strokes, cognitive and memory problems, depression, anxiety and migraine headaches, according to a comprehensive analysis of federal health data by researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care system.

Additionally, the post-COVID brain is associated with movement disorders, from tremors and involuntary muscle contractions to epileptic seizures, hearing and vision abnormalities, and balance and coordination difficulties as well as other symptoms similar to what is experienced with Parkinson’s disease.

The findings are published Sept. 22 in Nature Medicine.

“Our study provides a comprehensive assessment of the long-term neurologic consequences of COVID-19,” said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University. “Past studies have examined a narrower set of neurological outcomes, mostly in hospitalized patients. We evaluated 44 brain and other neurologic disorders among both nonhospitalized and hospitalized patients, including those admitted to the intensive care unit. The results show the devastating long-term effects of COVID-19. These are part and parcel of long COVID. The virus is not always as benign as some people think it is.”

Overall, COVID-19 has contributed to more than 40 million new cases of neurological disorders worldwide, Al-Aly said.

Other than having a COVID infection, specific risk factors for long-term neurological problems are scarce. “We’re seeing brain problems in previously healthy individuals and those who have had mild infections,” Al-Aly said. “It doesn’t matter if you are young or old, female or male, or what your race is. It doesn’t matter if you smoked or not, or if you had other unhealthy habits or conditions.”

Few people in the study were vaccinated for COVID-19 because the vaccines were not yet widely available during the time span of the study, from March 2020 through early January 2021. The data also predates delta, omicron and other COVID variants.

A previous study in Nature Medicine led by Al-Aly found that vaccines slightly reduce—by about 20%—the risk of long-term brain problems. “It is definitely important to get vaccinated but also important to understand that they do not offer complete protection against these long-term neurologic disorders,” Al-Aly said.

The researchers analyzed about 14 million de-identified medical records in a database maintained by the U.S. Department of Veterans Affairs, the nation’s largest integrated health-care system. Patients included all ages, races and sexes.

They created a controlled data set of 154,000 people who had tested positive for COVID-19 sometime from March 1, 2020, through Jan. 15, 2021, and who had survived the first 30 days after infection. Statistical modeling was used to compare neurological outcomes in the COVID-19 data set with two other groups of people not infected with the virus: a control group of more than 5.6 million patients who did not have COVID-19 during the same time frame; and a control group of more than 5.8 million people from March 2018 to December 31, 2019, long before the virus infected and killed millions across the globe.

The researchers examined brain health over a year-long period. Neurological conditions occurred in 7% more people with COVID-19 compared with those who had not been infected with the virus. Extrapolating this percentage based on the number of COVID-19 cases in the U.S., that translates to roughly 6.6 million people who have suffered brain impairments associated with the virus.

Memory problems—colloquially called brain fog—are one of the most common brain-related, long-COVID symptoms. Compared with those in the control groups, people who contracted the virus were at a 77% increased risk of developing memory problems. “These problems resolve in some people but persist in many others,” Al-Aly said. “At this point, the proportion of people who get better versus those with long-lasting problems is unknown.”

Interestingly, the researchers noted an increased risk of Alzheimer’s disease among those infected with the virus. There were two more cases of Alzheimer’s per 1,000 people with COVID-19 compared with the control groups. “It’s unlikely that someone who has had COVID-19 will just get Alzheimer’s out of the blue,” Al-Aly said. “Alzheimer’s takes years to manifest. But what we suspect is happening is that people who have a predisposition to Alzheimer’s may be pushed over the edge by COVID, meaning they’re on a faster track to develop the disease. It’s rare but concerning.”

Also compared to the control groups, people who had the virus were 50% more likely to suffer from an ischemic stroke, which strikes when a blood clot or other obstruction blocks an artery’s ability to supply blood and oxygen to the brain. Ischemic strokes account for the majority of all strokes, and can lead to difficulty speaking, cognitive confusion, vision problems, the loss of feeling on one side of the body, permanent brain damage, paralysis and death.

“There have been several studies by other researchers that have shown, in mice and humans, that SARS-CoV-2 can attack the lining of the blood vessels and then then trigger a stroke or seizure,” Al-Aly said. “It helps explain how someone with no risk factors could suddenly have a stroke.”

Overall, compared to the uninfected, people who had COVID-19 were 80% more likely to suffer from epilepsy or seizures, 43% more likely to develop mental health disorders such as anxiety or depression, 35% more likely to experience mild to severe headaches, and 42% more likely to encounter movement disorders. The latter includes involuntary muscle contractions, tremors and other Parkinson’s-like symptoms.

COVID-19 sufferers were also 30% more likely to have eye problems such as blurred vision, dryness and retinal inflammation; and they were 22% more likely to develop hearing abnormalities such as tinnitus, or ringing in the ears.

“Our study adds to this growing body of evidence by providing a comprehensive account of the neurologic consequences of COVID-19 one year after infection,” Al-Aly said.

Long COVID’s effects on the brain and other systems emphasize the need for governments and health systems to develop policy, and public health and prevention strategies to manage the ongoing pandemic and devise plans for a post-COVID world, Al-Aly said. “Given the colossal scale of the pandemic, meeting these challenges requires urgent and coordinated—but, so far, absent—global, national and regional response strategies,” he said.

COVID raises risk of long-term brain injury, large U.S. study finds

Authors: Julie Steenhuysen September 22, 2022 Yahoo News

People who had COVID-19 are at higher risk for a host of brain injuries a year later compared with people who were never infected by the coronavirus, a finding that could affect millions of Americans, U.S. researchers reported on Thursday.

The year-long study, published in Nature Medicine, assessed brain health across 44 different disorders using medical records without patient identifiers from millions of U.S. veterans.

Brain and other neurological disorders occurred in 7% more of those who had been infected with COVID compared with a similar group of veterans who had never been infected. That translates into roughly 6.6 million Americans who had brain impairments linked with their COVID infections, the team said.

“The results show the devastating long-term effects of COVID-19,” senior author Dr. Ziyad Al-Aly of Washington University School of Medicine said in a statement.

Al-Aly and colleagues at Washington University School of Medicine and the Veterans Affairs St. Louis Health Care System studied medical records from 154,000 U.S. veterans who had tested positive for COVID from March 1, 2020 to Jan. 15, 2021.

They compared these with records from 5.6 million patients who did not have COVID during the same time frame, and another group of 5.8 million people from the period just before the coronavirus arrived in the United States.

Al-Aly said prior studies looked at a narrower group of disorders, and were focused largely on hospitalized patients, whereas his study included both hospitalized and non-hospitalized patients.

Memory impairments, commonly referred to as brain fog, were the most common symptom. Compared with the control groups, people infected with COVID had a 77% higher risk of developing memory problems.

People infected with the virus also were 50% more likely to have an ischemic stroke, which is caused by blood clots, compared with the never infected group.

Those who had COVID were 80% more likely to have seizures, 43% more likely to have mental health issues, such as anxiety or depression, 35% more likely to have headaches and 42% more likely to suffer movement disorders, such as tremors, compared with the control groups.

Researchers said governments and health systems must devise plans for a post-COVID world.

“Given the colossal scale of the pandemic, meeting these challenges requires urgent and coordinated – but, so far, absent – global, national and regional response strategies,”

Opinions | How long covid reshapes the brain — and how we might treat it

Authors: Wes Ely August 25, 2022 The Washington Post

The young man pulled something from behind both ears. “I can’t hear anything without my new hearing aids,” said the 32-year-old husband and father. “My body is broken, Doc.” Once a fireman and emergency medical technician, he’d had covid more than 18 months before and was nearly deaf. He was also newly suffering from incapacitating anxiety, cognitive impairment and depression. Likewise, a 51-year-old woman told me through tears: “It’s almost two years. My old self is gone. I can’t even think clearly enough to keep my finances straight.” These are real people immersed in the global public health catastrophe of long covid, which the medical world is struggling to grasp and society is failing to confront.

As such stories clearly indicate, covid is biologically dangerous long after the initial viral infection. One of the leading hypotheses behind long covid is that the coronavirus is somehow able to establish a reservoir in tissues such as the gastrointestinal tract. I believe the explanation for long covid is more sinister.

The science makes it increasingly clear that covid-19 turns on inflammation and alters the nervous system even when the virus itself seems to be long gone. The virus starts by infecting nasal and respiratory lining cells, and the resulting inflammation sends molecules through the blood that trigger the release of cytokines in the brain. This can happen even in mild covid cases. Through these cell-to-cell conversations, cells in the nervous system called microglia and astrocytes are revved up in ways that continue for months — maybe years. It’s like a rock weighing down on the accelerator of a car, spinning its engine out of control. All of this causes injury to many cells, including neurons. It is past time we recognized this fact and began incorporating it into the ways we care for those who have survived covid.

For too long, the mysteries of long covid led many health-care professionals to dismiss it as an untreatable malady or a psychosomatic illness without a scientific basis. Some of this confusion comes down to the stuttering cadence of scientific progress. Early in the pandemic, autopsy findings from patients who died of covid “did not show encephalitis or other specific brain changes referable to the virus” as one report noted. Patients with profound neurological illnesses resulting from covid-19 had no trace of the virus in the cerebrospinal fluid encasing their brains.

These studies left most medical professionals mistakenly convinced that the virus was not damaging the brain. Accordingly, we narrowed our focus to the lungs and heart and then scratched our heads in wonder at the coma and delirium found in more than 80 percent of covid ICU patients. A robust study from the Netherlands showed that at least 12.5 percent of covid patients end up with long covid three months afterward, yet because “brain fog” wasn’t identified until later in the pandemic, these investigators didn’t include cognitive problems or mental health disorders in the data they collected. Thus, this otherwise beautifully executed study almost certainly underestimated the rate of long covid.

Since the early days of the pandemic, we’ve learned a great deal about the neurological effects of SARS-CoV-2. Earlier this year, the UK Biobank neuroimaging study showed that even mild covid can lead to an overall reduction in the size of the brain, with notable effects in the frontal cortex and limbic system. These findings help explain the profound anxiety, depression, memory loss and cognitive impairment experienced by so many long-covid patients.

new study published in the Lancet of more than 2.5 million people matched covid-19 patients with non-covid patients to determine the rate of recovery from mental health complaints and neurological deficits like the depression and brain fog in my own patients. What it revealed is partly encouraging and partly devastating: The anxiety and mood disorders in long covid tend to resolve over months, while serious dementia-like problems, psychosis and seizures persist at two years.

New study suggests covid increases risks of brain disorders

Authors: Frances Stead Sellers Fri, August 19, 2022  Washington Post

A study published this week in the Lancet Psychiatry showed increased risks of some brain disorders two years after infection with the coronavirus, shedding new light on the long-term neurological and psychiatric aspects of the virus.

The analysis, conducted by researchers at the University of Oxford and drawing on health records data from more than 1 million people around the world, found that while the risks of many common psychiatric disorders returned to normal within a couple of months, people remained at increased risk for dementia, epilepsy, psychosis and cognitive deficit (or brain fog) two years after contracting covid. Adults appeared to be at particular risk of lasting brain fog, a common complaint among coronavirus survivors.

The study was a mix of good and bad news findings, said Paul Harrison, a professor of psychiatry at the University of Oxford and the senior author of the study. Among the reassuring aspects was the quick resolution of symptoms such as depression and anxiety.

“I was surprised and relieved by how quickly the psychiatric sequelae subsided,” Harrison said.

David Putrino, director of rehabilitation innovation at Mount Sinai Health System in New York, who has been studying the lasting impacts of the coronavirus since early in the pandemic, said the study revealed some very troubling outcomes.

“It allows us to see without a doubt the emergence of significant neuropsychiatric sequelae in individuals that had covid and far more frequently than those who did not,” he said.

Because it focused only on the neurological and psychiatric effects of the coronavirus, the study authors and others emphasized that it is not strictly long-covid research.

“It would be overstepping and unscientific to make the immediate assumption that everybody in the [study] cohort had long covid,” Putrino said. But the study, he said, “does inform long-covid research.”

Between 7 million and 23 million people in the United States have long covid, according to recent government estimates – a catchall term for a wide range of symptoms including fatigue, breathlessness and anxiety that persist weeks and months after the acute infection has subsided. Those numbers are expected to rise as the coronavirus settles in as an endemic disease.

The study was led by Maxime Taquet, a senior research fellow at the University of Oxford who specializes in using big data to shed light on psychiatric disorders.

The researchers matched almost 1.3 million patients with a diagnosis of covid-19 between Jan. 20, 2020, and April 13, 2022, with an equal number of patients who had other respiratory diseases during the pandemic. The data, provided by electronic health records network TriNetX, came largely from the United States but also included data from Australia, Britain, Spain, Bulgaria, India, Malaysia and Taiwan.

The study group, which included 185,000 children and 242,000 older adults, revealed that risks differed according to age groups, with people age 65 and older at greatest risk of lasting neuropsychiatric affects.

For people between the ages of 18 and 64, a particularly significant increased risk was of persistent brain fog, affecting 6.4 percent of people who had had covid compared with 5.5 percent in the control group.

Six months after infection, children were not found to be at increased risk of mood disorders, although they remained at increased risk of brain fog, insomnia, stroke and epilepsy. None of those affects were permanent for children. With epilepsy, which is extremely rare, the increased risk was larger.

The study found that 4.5 percent of older people developed dementia in the two years after infection, compared with 3.3 percent of the control group. That 1.2-point increase in a diagnosis as damaging as dementia is particularly worrisome, the researchers said.

The study’s reliance on a trove of de-identified electronic health data raised some cautions, particularly during the tumultuous time of the pandemic. Tracking long-term outcomes may be hard when patients may have sought care through many different health systems, including some outside the TriNetX network.

“I personally find it impossible to judge the validity of the data or the conclusions when the data source is shrouded in mystery and the sources of the data are kept secret by legal agreement,” said Harlan Krumholz, a Yale scientist who has developed an online platform where patients can enter their own health data.

Taquet said the researchers used several means of assessing the data, including making sure it reflected what is already known about the pandemic, such as the drop in death rates during the omicron wave.

Also, Taquet said, “the validity of data is not going to be better than validity of diagnosis. If clinicians make mistakes, we will make the same mistakes.”

The study follows earlier research from the same group, which reported last year that a third of covid patients experienced mood disorders, strokes or dementia six months after infection with the coronavirus.

While cautioning that it is impossible to make full comparisons among the effects of recent variants, including omicron and its subvariants, which are currently driving infections, and those that were prevalent a year or more ago, the researchers outlined some initial findings: Even though omicron caused less severe immediate symptoms, the longer-term neurological and psychiatric outcomes appeared similar to the delta waves, indicating that the burden on the world’s health-care systems might continue even with less-severe variants.

Hannah Davis, a co-founder of the Patient-Led Research Collaborative, which studies long covid, said that finding was meaningful. “It goes against the narrative that omicron is more mild for long covid, which is not based on science,” Davis said.

“We see this all the time,” Putrino said. “The general conversation keeps leaving out long covid. The severity of initial infection doesn’t matter when we talk about long-term sequalae.

Long COVID study looks at why some can’t shake dizziness, fatigue and more

Authors: Helena Oliviero, The Atlanta Journal-Constitution

Georgia residents among thousands needed for a massive study to discover how the virus causes lingering symptoms.

Back in the summer of 2020, when the pandemic was still new and hospitals were overflowing, Emory Healthcare opened a facility to treat a perplexing group of COVID-19 survivors.

The patients had withstood the virus’s initial onslaught but couldn’t shake some of the symptoms.

At the time, Dr. Alex Truong thought the long COVID clinic might be needed for a year, maybe two.

But long COVID — a mysterious constellation of ailments that can go on for many weeks or months — has become a bigger problem than Truong could have ever imagined.

In the U.S. alone, 1 in 5 of the adults stricken with COVID-19 have developed conditions that could be considered long COVID, according to a recent study by the Centers for Disease Control and Prevention. Symptoms range from brain fog and unrelenting fatigue to gastric and cardiac issues. Among those 65 and older, the estimates are even higher — 1 in 4.

That translates into millions of Americans and more than 300,000 Georgians.

Other estimates vary wildly. There is no test for long COVID. No official statistics exist.

Clinicians at the Emory clinic have treated more than 1,000 COVID survivors. There’s now a four-month waiting list to be seen at the clinic.ExploreComplete coverage of COVID-19 in Georgia

“It’s been shocking,” said Truong, who is co-director of the clinic,located at Emory University Hospital Midtown. “I’ve never seen, with other infections, such widespread, all-over-the-body symptoms for this long.”

COVID can wreak havoc on a person’s body and damage organs – the lungs, heart, kidneys and liver. Experts worry that people who are infected multiple times have increased chances of developing long COVID.

How is long COVID defined?

A recent CDC study says that 1 in 5 of U.S. adults stricken with COVID-19 have developed conditions that could be considered long COVID, which the agency defines as symptoms lasting at least four weeks after infection.

The CDC says the following symptoms are the most common for this complex and poorly understood condition:

  • Tiredness or fatigue that interferes with daily life
  • Difficulty breathing, shortness of breath, chest pain
  • Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
  • Headache
  • Sleep problems
  • Anxiety
  • Digestive issues
  • Joint or muscle pain

“With COVID, we tend to think about the hospitalizations and deaths, and then we kind of stop there sometimes,” said Dr. Tiffany Walker, who has treated long COVID patients at Grady Memorial Hospital. “I don’t want to paint the picture of everybody’s debilitated, but some people are, and it’s people that don’t expect it. The times that people have cried in my office because they’re just so overwhelmed is like more than anything I’ve experienced before in clinical practice.”

Walker now leads a long COVID study at Grady, which is part of a massive National Institutes of Health effort to find the connection between seemingly unrelated symptoms that have afflicted patients and confounded physicians.

Scientists still do not know how the virus triggers such a wide range of problems, from minor to incapacitating, or why issues emerge in some patients but not in others, or what exactly the risk factors are for developing them.

What’s more, there is no specific treatment for longCOVID. Instead, the current approach is to deal with each symptom individually.

It’s often hard to offer satisfying answers to patients. “It’s just very upsetting and really challenging,” Walker said. “As a physician, you really want to be able to provide a prognosis at least, at a minimum to be able to express to them, this is what you can expect.”

But doctors “don’t know enough to know what the course is going to be and who’s going to get better and who isn’t, and you don’t know enough about how to treat those that aren’t getting better,” she said.

And the world’s leading health organizations don’t even have a standard definition of what constitutes long COVID, Truong said. The CDC defines long COVID, which it calls Post-COVID Conditions, as symptoms lasting four weeks or longer after infection. The World Health Organization says people cross over into long COVID after symptoms persist for at least three months.

In 2021, 60% of patients at the Emory and Grady long COVID clinics enrolled in a study aimed at gathering more information on the illness. At the time of their enrollment, patients had already been dealing with COVID symptoms for an average of 107 days.

Even people who have mild or asymptomatic COVID-19 infections can have new health problems crop up months after they’ve tested negative.

Remaining vigilant

The CDC’s study evaluated electronic medical records for nearly 2 million people. The agency compared those who had been infected with the coronavirus and those who had not. The analysis found 38% percent of the COVID patients developed one or more new health problems, compared to 16% percent of the non-COVID patients. The health problems of about 21% of the younger COVID patients in the study, those ages 18 to 64, and nearly 27% of the older people, 65 and up, could be attributed to long COVID. The study did not look at vaccination status.

A growing number of studies suggest that getting a COVID vaccine can reduce — though not eliminate — the risk of longer-term symptoms.

Some experts think that today’s omicron strains pose a lower risk for long COVID than previous variants. But they caution: Even if omicron is less likely to cause long-lasting symptoms, particularly for people who have been vaccinated, the actual number of long COVID sufferers will still grow due to the high infection rate.

It’s often hard to determine whether health problems that emerge after a case of COVID are truly triggered by the virus.

Lead Nurse Practitioner Lori Reed, who works at the Piedmont Pulmonary COVID Recovery clinic, said some patients dealing with preexisting conditions may be more aware of them after coronavirus infections. That means it’s important for clinicians to obtain thorough medical histories to pinpoint when symptoms, such as dizziness, memory loss and headaches, started and when they worsened, she said.

“One that comes up all the time is asthma because asthma can develop at any point in life,” Reed said. “We know, historically, viral illnesses can cause asthma onset, so COVID can cause asthma onset. But, with women, hormonal changes and menopause can also cause onset.”

Reed recommends patients see a doctor after a COVID infection to rule out COVID-related damage to the body, and she urges people to remain vigilant of any sign of new problems.ExploreFrom November: Georgia long-COVID patients fight for benefits, legitimacy

“Pay attention to subtle things that some people may write off,” she said. “Talk to your doctor about brain fog or things like, ‘I just forgot what I was going to make for dinner,’ or ‘You know, that bill came in, and I forgot to pay for it.’”

At long COVID clinics, a team of specialists — cardiologists, pulmonologists, neurologists, psychiatrists and others — work together to treat patients. Often, the patients undergo a comprehensive evaluation, including a series of lab tests and imaging tests, to rule out other undiagnosed medical conditions.

Lacking established therapies for long COVID symptoms, doctors often rely on approaches that have been used for other ailments with similar symptoms.

“It’s been shocking. I’ve never seen, with other infections, such widespread, all-over-the-body symptoms for this long.”

– Dr. Alex Truong, co-director of Emory Healthcare’s post-COVID clinic

Neurological stimulants such as Adderall have shown to be effective at improving energy and focus. Albuterol, an inhaled medicine frequently used to treat asthma, can improve breathing. Other medications, physical therapy and cognitive programs also can be helpful.

“I would say to people who get COVID, you didn’t ask to get COVID, and you don’t deserve to fall ill and not have answers,” said Reed. “Reach out to somebody to at least be seen and evaluated because we can do things to get you feeling better. If we can’t reverse the long-term consequences, we can at least improve your quality of life.”

A high-stakes undertaking

Close to 1,000 people in Georgia — and at least 17,000 adults across the country — are being recruited for the massive NIH study called Researching COVID to Enhance Recovery (RECOVER). Its goal is to answer fundamental questions about exactly how the virus causes long COVID, which ultimately could lead to better, more tailored treatments.

The study sites in Atlanta — Emory Hope Clinic, Grady, Morehouse School of Medicine, the Atlanta Veterans Affairs Healthcare System and Kaiser Permanente of Georgia — will work together and are slated to receive a total of about$20 million over four years for the high-stakes undertaking.

The NIH study

The Atlanta sites for the NIH are still actively recruiting patients who have had COVID-19 in the past 30 days, as well as those who have never been infected. Click here for more information.

Walker, from Grady, said clinicians have been working to recruit a diverse group of adults, and are seeking three categories of participants: those who have COVID right now, those with long COVID, and others who have never had COVID. Finding people who have never had the illness is getting increasingly difficult with an ever-changing virus and continued waves of infections.

Plenty of theories have formed around long COVID. Some researchers think people suffer prolonged symptoms because they have never really shaken COVID-19, though they think they have. Instead, the virus is still hiding in their bodies, damaging nerves and other organs. Other research suggeststhe virus may be gone, but it causes the immune system to go haywire and attack the body.

There’s also research that indicates certain medical conditions may play a role in who develops long COVID, such as Type 2 diabetes, or a reactivation of Epstein-Barr virus, which infects most people when they are young.

‘A monster’

In July 2020, Latoshia Allen Perrymond fell ill with COVID. Within a week, the 52-year-old Stone Mountain woman was struggling to catch her breath. She ended up hospitalized — for four months.

Though she survived, COVID damaged her heart and lungs. She said she’s been struggling mightily ever since. Dependent on oxygen around the clock, the former caregiver now relies on family members to help care for her.

She can no longer go on walks with her husband or cook big meals, or even sleep lying flat.

In late March, she eagerly joined the NIH study at Grady.

Like other participants in the NIH RECOVER study, she’s undergoing physical assessments.

“I feel good about the study because it means that I’m part of the answers,” she said. “I’m willing to do whatever they need because this COVID and long COVD is a monster and it’s still creepy. I’m learning to live with this new norm for me, but I hope that I can get better.”

Doctors are also eager for more answers.

“My hope is to find a pathology that unifies all of these symptoms,” said Truong. “My hope is, as the pandemic progresses, the variants become less virulent and less likely to cause long haul issues, and more and more patients are getting vaccinated. I hope we learn from this pandemic so that, when the next pandemic comes, we are a lot smarter, a lot more nimble in our approach, and more aware of the long haul issues.”

For now, the best way to try to avoid long COVID is to try to avoid the virus, Truong said. Get vaccinated and boosted and wear masks – especially indoors around crowds of people.

“It’s as simple as that,” he said. “But, unfortunately, I don’t think people want to hear it.”

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