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Id Subject Object Predicate Lexical cue
T1 0-69 Sentence denotes Potential neurological manifestations of COVID-19: a narrative review
T2 70-72 Sentence denotes J.
T3 73-75 Sentence denotes V.
T4 76-93 Sentence denotes PERGOLIZZI ET AL.
T5 94-115 Sentence denotes POSTGRADUATE MEDICINE
T6 117-125 Sentence denotes Abstract
T7 126-134 Sentence denotes ABSTRACT
T8 135-222 Sentence denotes Neurological manifestations are increasingly reported in a subset of COVID-19 patients.
T9 223-424 Sentence denotes Previous infections related to coronaviruses, namely Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) also appeared to have neurological effects on some patients.
T10 425-650 Sentence denotes The viruses associated with COVID-19 like that of SARS enters the body via the ACE-2 receptors in the central nervous system, which causes the body to balance an immune response against potential damage to nonrenewable cells.
T11 651-729 Sentence denotes A few rare cases of neurological sequelae of SARS and MERS have been reported.
T12 730-932 Sentence denotes A growing body of evidence is accumulating that COVID-19, particularly in severe cases, may have neurological consequences although respiratory symptoms nearly always develop prior to neurological ones.
T13 933-1053 Sentence denotes Patients with preexisting neurological conditions may be at elevated risk for COVID-19-associated neurological symptoms.
T14 1054-1266 Sentence denotes Neurological reports in COVID-19 patients have described encephalopathy, Guillain-Barré syndrome, myopathy, neuromuscular disorders, encephalitis, cephalgia, delirium, critical illness polyneuropathy, and others.
T15 1267-1410 Sentence denotes Treating neurological symptoms can pose clinical challenges as drugs that suppress immune response may be contraindicated in COVID-19 patients.
T16 1411-1519 Sentence denotes It is possible that in some COVID-19 patients, neurological symptoms are being overlooked or misinterpreted.
T17 1520-1691 Sentence denotes To date, neurological manifestations of COVID-19 have been described largely within the disease trajectory and the long-term effects of such manifestations remain unknown.
T18 1693-1705 Sentence denotes Introduction
T19 1706-1956 Sentence denotes The neuroinvasive potential of the Severe Acute Respiratory Syndrome novel coronavirus, SARS-CoV-2, is being recognized, with enhanced awareness that the associated infection, Coronavirus Diseases 2019 (COVID-19), might result in neurological injury.
T20 1957-2112 Sentence denotes Indeed, there is a growing body of evidence to suggest that a subset of COVID-19 patients will experience neurological manifestations of the infection [1].
T21 2113-2557 Sentence denotes Since genomic studies show that the SARS-CoV-2 virus has similar homological sequences with two of its beta-coronavirus predecessors, the SARS-CoV associated with Severe Acute Respiratory Syndrome (SARS) [2] and the virus associated with Middle Eastern Respiratory Syndrome (MERS) [3], it is helpful to review the neurological symptoms of these two earlier diseases as the plausible link between COVID-19 and neurological symptoms are explored.
T22 2558-2694 Sentence denotes Furthermore, the pathophysiological pathways of these three conditions (COVID-19, SARS, and MERS) might be expected to be similar [4–6].
T23 2695-2851 Sentence denotes Neurotropism has been observed in both MERS and SARS [7–9], and there are early findings of certain neurological manifestations in COVID-19 patients [4,10].
T24 2852-2994 Sentence denotes The RNA of the SARS-CoV-2 virus has been identified in the cerebrospinal fluid of a COVID-19 patient, demonstrating its neurotropic potential.
T25 2995-3220 Sentence denotes It is clinically relevant to determine how the SARS-CoV-2 virus can access the central nervous system (CNS) and whether the neuronal injury caused by the virus might be connected to the injury of the autonomic nervous system.
T26 3221-3349 Sentence denotes The transmission of a novel infectious pathogen among humans such as the SARS-CoV-2 may be complicated, but it is far from rare.
T27 3350-3442 Sentence denotes As many as 75% of emerging human infections have some connection to a zoonotic disease [11].
T28 3443-3801 Sentence denotes Typically, viral, bacterial, fungal, or parasitical pathogens may emerge due to one or a combination of factors: human and animal interaction, changes in human or animal behavior, consumption of exotic animal foods, globalization, world travel, or things that disrupt human and animal interactions, such as wars, natural disasters, and environmental changes.
T29 3802-3987 Sentence denotes The pathogen itself may play a role in its pattern of emergence by mutation; in some instances, humans may facilitate the rapid progress of these mutations by the use of antimicrobials.
T30 3988-4105 Sentence denotes Thus, while often multifactorial and complex, the sudden emergence of a novel infectious agent is not a novelty [12].
T31 4106-4252 Sentence denotes The novel SARS-CoV-2 virus, which first appeared in 2019, is just one of several coronaviruses that have caused epidemics in the past two decades.
T32 4253-4447 Sentence denotes These pathogens are sometimes able to adapt to new hosts, as occurred with the zoonotic SARS-CoV-2 virus, which appears to have originated in bats, then rapidly accommodated to human hosts [13].
T33 4448-4615 Sentence denotes Coronaviruses are single-stranded, positive-sense, enveloped RNA viruses in the nidovirales order that are categorized into four genera: alpha, beta, gamma, and delta.
T34 4616-4697 Sentence denotes The SARS-CoV-2 virus associated with the COVID-19 epidemic is a beta-coronavirus.
T35 4698-4818 Sentence denotes Seven known coronaviruses affect humans: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2.
T36 4819-4863 Sentence denotes Many coronavirus-related illnesses are mild.
T37 4864-4959 Sentence denotes In fact, coronaviruses were first studied in the 1960s as being agents of the common cold [14].
T38 4960-5104 Sentence denotes Nevertheless, of these viruses, only MERS-CoV, SARS-CoV, and SARS-CoV-2 are associated with potentially severe symptoms and fatal outcomes [15].
T39 5105-5197 Sentence denotes Once in the body, viruses may invade the CNS through hematogenous spread defined by viremia.
T40 5198-5427 Sentence denotes Viruses may also enter the CNS through retrograde neuronal dissemination, which occurs when the virus infects peripheral neurons, subsequently spreading to the spine and brain by way of the existing neuronal transport mechanisms.
T41 5428-5629 Sentence denotes It is the aim of this narrative review to describe what is known about neurological manifestations of SARS, MERS, and COVID-19, with special emphasis on reports about neurological symptoms in COVID-19.
T42 5631-5638 Sentence denotes Methods
T43 5639-5912 Sentence denotes The authors searched the peer-reviewed medical literature using the PubMed database of the National Institutes of Med for COVID-19 resources searching for ‘neurology,’ ‘neurological symptoms,’ and ‘neuropathy.’ The bibliographies of relevant articles were searched as well.
T44 5913-6046 Sentence denotes The literature on COVID-19 is vast and expanding rapidly, but many articles are short commentaries, case studies, and correspondence.
T45 6047-6108 Sentence denotes The search covers materials published through 17 August 2020.
T46 6109-6263 Sentence denotes This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
T47 6265-6272 Sentence denotes Results
T48 6273-6506 Sentence denotes Far more is known and reported on neurological complications with SARS and MERS than for COVID-19 although the nature of the pandemic and the clinicians reporting from the front lines is rapidly generating a large body of literature.
T49 6507-6784 Sentence denotes In a systematic review that identified COVID-19 cases with neurological complications (n = 82), the mean age of the patient was 62.3 years, 37.8% were female, and 48.8% developed cerebrovascular insults, 28% neuromuscular disorders, and 23% encephalitis or encephalopathy [16].
T50 6786-6837 Sentence denotes Viral entry and potential neurological consequences
T51 6838-7099 Sentence denotes The viruses associated with both SARS and COVID-19 enter the brain via a process involving the angiotensin-converting enzyme (ACE)-2 receptors located in the CNS [17–19], unlike the MERS virus, which gains entry via the plasma membrane or in the endosomes [20].
T52 7100-7215 Sentence denotes ACE-2 receptors are expressed in many parts of the body and are particularly densely expressed in the nasal mucosa.
T53 7216-7420 Sentence denotes Coronaviruses that enter the body via the nasal mucosa may disrupt the nasal endothelium, cross the epithelial barrier, and then directly enter the lymphatic or circulatory system, accessing the CNS [21].
T54 7421-7529 Sentence denotes The SARS-CoV has been detected in the brain, and it is thought entry occurred by way of the olfactory nerve.
T55 7530-7716 Sentence denotes Since there have been studies that located the SARS-CoV virus in the CNS but not the lung, it suggests that there is a direct pathway from the olfactory point of entry into the CNS [22].
T56 7717-7982 Sentence denotes Alternatively, a high viral load in the brain following a pulmonary infection might mean the virus entered the brain from the respiratory system; e.g., the vagus nerve links the respiratory system to the nucleus ambiguous and solitary tract nuclei of the brainstem.
T57 7983-8146 Sentence denotes It has been speculated that the cardiorespiratory center of the brain may be involved in the severe acute respiratory distress in some patients with COVID-19 [23].
T58 8147-8385 Sentence denotes The more common form of respiratory failure in COVID-19 patients is Type 1 (gas exchange dysfunction resulting in hypoxia and low levels of carbon dioxide), which is more likely to be associated with pneumonia than brain dysfunction [24].
T59 8386-8615 Sentence denotes Type 2 respiratory failure, which involves both hypoxia and high levels of carbon dioxide due to ventilatory failure would be more suggestive of neurological dysfunction, and this occurs less frequently in COVID-19 patients [25].
T60 8616-8836 Sentence denotes Any viral invader of the CNS creates stress within the body, because the host must balance its natural immune response to destroy the pathogen while, at the same time, minimizing damage to nearby nonrenewable cells [26].
T61 8837-8978 Sentence denotes Once in the CNS, viruses that affect neurons are far more dangerous than viruses that target the leptomeninges, which can restore themselves.
T62 8979-9116 Sentence denotes The CNS has a highly nuanced system of responses to viruses, which can cause considerable harm to the body should it become uncontrolled.
T63 9117-9331 Sentence denotes Coronaviruses such as the SARS-CoV-2 can enter the body via the nasal mucosa and may disrupt the nasal endothelium, cross the epithelial barrier, and then enter the CNS via the lymphatic or circulatory system [21].
T64 9332-9515 Sentence denotes The blood-brain barrier has a pore size of about 1 nm and coronaviruses are substantially larger [9], and this likely protects the brain from coronavirus invasion in many individuals.
T65 9516-9776 Sentence denotes However, neuroinvasive viruses can cross the blood-brain barrier by brain viremia, inflammatory processes (making microvascular endothelial cells vulnerable), or infecting leukocytes that then cross the blood-brain barrier in the manner of a Trojan horse [27].
T66 9777-9980 Sentence denotes The entry of the virus via the olfactory endothelium with transit of the virus across the cribriform plate would allow the virus to enter the brain by circumventing the blood-brain barrier entirely [27].
T67 9981-10339 Sentence denotes In theory at least, the coronavirus could invade the CNS using a passive mechanism such as hematogenous spread; in this case, the virus goes dormant and is carried toward the CNS, only to re-activate at some point to infect endothelial cells of the blood-brain barrier or infect leukocytes that then act as the reservoir for further viral dissemination [28].
T68 10340-10464 Sentence denotes The neurological symptoms associated with the H1N1 influenza virus had earlier been explained by an autoimmunity model [29].
T69 10465-10676 Sentence denotes The autoimmunity model of coronavirus infection of the CNS, likewise unproven, maintains that neural tissues and blood vessels perceive both viral and myelin antigens as the same because of autoreactive T-cells.
T70 10677-10757 Sentence denotes Autoimmunity would be limited to patients who were genetically predisposed [29].
T71 10758-10972 Sentence denotes The SARS-CoV-2 associated with COVID-19 belongs to the same clade of beta-coronaviruses as the MERS-CoV and the SARS-CoV viruses, although its homological sequence more closely resembles SARS-CoV than MERS-CoV [2].
T72 10973-11195 Sentence denotes The respiratory symptoms that occur in genetically related beta-coronaviruses, such as MERS-CoV and SARS-CoV are similar, two infections with which the global healthcare community has had years of clinical experience [30].
T73 11196-11342 Sentence denotes While it cannot be stated unequivocally that the neurological symptoms of these viral infections will be the same, it forms a good starting point.
T74 11344-11379 Sentence denotes Middle eastern respiratory syndrome
T75 11380-11533 Sentence denotes MERS was first identified in September 2012 in a 60-year-old man in Jeddah, Saudi Arabia, who presented with pneumonia complicated by renal failure [31].
T76 11534-11695 Sentence denotes Sporadic cases were reported outside of the Middle East up until 2015, when an outbreak in South Korea occurred with 186 confirmed infections and 38 deaths [32].
T77 11696-11837 Sentence denotes MERS has established associations with encephalomyelitis, vasculitis, Guillain-Barré syndrome (GBS), and encephalitis of the brain stem [21].
T78 11838-11991 Sentence denotes The clinical course of MERS ranges from asymptomatic cases (about 4%) to severe pneumonia with multiorgan involvement and negative patient outcomes [15].
T79 11992-12162 Sentence denotes While pulmonary, gastrointestinal, renal, and hematological complications have been reported in MERS patients, there are fewer reports of neurological complications [15].
T80 12163-12255 Sentence denotes In fact, the MERS-CoV virus has never been isolated from neural tissue in human beings [28].
T81 12256-12478 Sentence denotes In a study of 737 hospitalized MERS patients in South Korea, the most commonly reported symptoms were respiratory symptoms (13.6%), fever (11.1%), fatigue (11.1%), myalgia (9.2%), and gastrointestinal symptoms (7.5%) [32].
T82 12479-12615 Sentence denotes In a study of 23 MERS patients from South Korea, 17.4% experienced neurological symptoms either during or following MERS treatment [33].
T83 12616-12728 Sentence denotes These neurological complications occurred about two to three weeks after the onset of respiratory symptoms [33].
T84 12729-12851 Sentence denotes A study from Saudi Arabia (n = 70) reported that 24.7% of MERS patients experienced confusion and 8.6% had a seizure [34].
T85 12852-12953 Sentence denotes In this study, fever was present in 61.4% of patients, dyspnea occurred in 60%, an 54.3% had a cough.
T86 12954-13093 Sentence denotes MERS symptoms were typically severe with 70% of those hospitalized in this study requiring intensive care and 60% of this cohort died [34].
T87 13094-13271 Sentence denotes The literature reports a fatal case of a 34-year-old woman with diabetes hospitalized for MERS, who two weeks after diagnosis developed a headache with nausea and vomiting [15].
T88 13272-13514 Sentence denotes An urgent computed tomography scan showed right frontal lobe intracerebral hemorrhage with massive brain edema; laboratory findings showed disseminated intravascular coagulation, including thrombocytopenia and a prolonged coagulation profile.
T89 13515-13697 Sentence denotes In another case, a 28-year-old man was hospitalized in the intensive care unit for MERS complicated by bacterial pneumonia and had to be put on a ventilator for respiratory distress.
T90 13698-13826 Sentence denotes Unfortunately, after initial improvement, he reported weakness and tingling in his legs that made it impossible for him to walk.
T91 13827-13994 Sentence denotes Using neuroimaging scans, cerebrospinal fluid analysis, nerve conduction velocity studies, and spinal imaging, a diagnosis was made of critical-illness polyneuropathy.
T92 13995-14166 Sentence denotes He was treated with intravenous (IV) immunoglobulin 400 mg/kg daily for five days and was discharged in 40 days; gradual improvement was noted over the next 6 months [15].
T93 14168-14201 Sentence denotes Severe acute respiratory syndrome
T94 14202-14275 Sentence denotes SARS broke out in Hong Kong, Taiwan, Canada, and other locations in 2003.
T95 14276-14374 Sentence denotes It has been reported to be associated with encephalitis, ischemic stroke, and polyneuropathy [35].
T96 14375-14459 Sentence denotes Seizures have been mentioned as the first symptom of SARS-related encephalitis [36].
T97 14460-14599 Sentence denotes In a necropsy study of eight patients who died of SARS, there was evidence of SARS-CoV infection in the brain cortex and hypothalamus [37].
T98 14600-14737 Sentence denotes Particles from the SARS-CoV virus have been found in the brains of patients infected with SARS, most frequently in brain neurons [37–39].
T99 14738-14883 Sentence denotes Murine studies found that intranasal injections of both MERS-CoV and SARS-CoV could enter the brain, presumably via the olfactory nerves [40,41].
T100 14884-15023 Sentence denotes Among the areas of the brain infected, the brain stem was a primary, but not exclusive, target for both MERS-CoV [41] and SARS-CoV [40,42].
T101 15024-15091 Sentence denotes Neurological sequelae of SARS have been only sporadically reported.
T102 15092-15332 Sentence denotes Acute olfactory neuropathy has been reported in a case study of a 27-year-old female SARS patient who was diagnosed with SARS in 2003, hospitalized, and recovered with combination therapy of antiviral therapy (ribivarin plus steroids) [43].
T103 15333-15394 Sentence denotes Fever persisted for about three weeks from onset of symptoms.
T104 15395-15521 Sentence denotes She was discharged from the hospital at around the same time she reported the paroxysmal bilateral loss of her sense of smell.
T105 15522-15706 Sentence denotes An otolaryngologic examination, biochemistry tests, and subsequent magnetic resonance imaging scans showed nothing unusual with no lesions that might account for her loss of olfaction.
T106 15707-15800 Sentence denotes Now 2 years after her recovery from SARS, she still has not regained her sense of smell [43].
T107 15801-16012 Sentence denotes The common causes of anosmia include structural defects in the nasal cavity or sinuses, head injury, brain trauma, brain lesions, or drug-induced loss of olfaction, and in her case, these could all be ruled out.
T108 16013-16108 Sentence denotes It was postulated that her anosmia was a coronavirus-induced form of olfactory neuropathy [43].
T109 16109-16177 Sentence denotes Neuromuscular symptoms associated with SARS have also been reported.
T110 16178-16277 Sentence denotes A 51-year-old woman in Taiwan developed probable SARS shortly after her husband was diagnosed [44].
T111 16278-16456 Sentence denotes She was hospitalized and intubated and had no evidence of respiratory syncytial virus; however, a bone-marrow biopsy showed evidence of infection-related hemophagocytic syndrome.
T112 16457-16583 Sentence denotes Her condition gradually improved and she was extubated, but she complained of weakness, numbness, and paresthesia in her legs.
T113 16584-16774 Sentence denotes Ten days after extubation, a neurological examination showed good mental clarity with intact cranial nerves, but symmetric loss of muscle strength in her legs and mild weakness in the hands.
T114 16775-16952 Sentence denotes These conditions improved slowly and two months later, a neurological examination reported only mild loss of leg strength and slight numbness in the toes of her right foot [44].
T115 16953-17127 Sentence denotes A case report from Hong Kong describes a 59-year-old woman with severe SARS who developed status epilepticus; evidence of the virus was found in her cerebrospinal fluid [45].
T116 17128-17285 Sentence denotes Another case report describes a pregnant patient with SARS who experienced a generalized convulsion with suspected nervous system invasion by the virus [46].
T117 17286-17468 Sentence denotes The neurological manifestations observed in SARS include peripheral axonal neuropathy and elevated muscle enzymes, which might be caused by extensive virus-driven vasculitis [38,47].
T118 17469-17577 Sentence denotes These were considered to be polyneuropathic and/or myopathic symptoms associated with critical illness [47].
T119 17579-17587 Sentence denotes COVID-19
T120 17588-17706 Sentence denotes Neurological symptoms have been sporadically reported in COVID-19 patients but have not yet been well studied [48,49].
T121 17707-17831 Sentence denotes The current body of evidence suggests that the SARS-CoV-2 can affect the nervous system in previously unsuspected ways [50].
T122 17832-17925 Sentence denotes The neuroinvasive capabilities of the SARS-CoV-2 doubtless exist but remain to be elucidated.
T123 17926-18053 Sentence denotes Observed neurological symptoms of COVID-19 include febrile seizures, convulsions, mental status changes, and encephalitis [51].
T124 18054-18211 Sentence denotes Among the most commonly reported possibly neurological symptoms of COVID-19 are nonspecific symptoms, such as headache, myalgia, dizziness, and fatigue [21].
T125 18212-18365 Sentence denotes In a study at a single center in China (n = 214), 36.4% (n = 78) of hospitalized COVID-19 patients had what were identified as neurological symptoms[52].
T126 18366-18540 Sentence denotes In a multicenter retrospective study from Europe of 417 patients who recovered from mild to moderate COVID-19, 86% reported olfactory dysfunction and 88% problems with taste.
T127 18541-18640 Sentence denotes In fact, in 12% of patients, the loss of the sense of smell was the first symptom of COVID-19 [53].
T128 18641-18933 Sentence denotes The loss of smell has emerged as being more prevalent among patients infected with COVID-19 than patients infected with other viruses or with other types of respiratory conditions [54] and has been recommended as a symptom that may help guide earlier diagnosis and treatment of COVID-19 [55].
T129 18934-19062 Sentence denotes In a meta-analysis (n = 1,627 patients, 10 studies), a loss of the sense of smell was reported in 53% of COVID-19 patients [55].
T130 19063-19163 Sentence denotes It appears that the frequency of neurological symptoms is associated with COVID-19 disease severity.
T131 19164-19422 Sentence denotes In the aforementioned study of 214 hospitalized patients with COVID-19 infection (41% severe and 59% non-severe disease), severe patients were more likely than non-severe patients to have neurologically related manifestations (45.5% vs. 30.2%, respectively).
T132 19423-19686 Sentence denotes In this study, the most frequently reported neurological manifestations for severe and non-severe patients, respectively, were acute cerebrovascular disease (5.7% vs. 0.8%), impaired consciousness (14.8% vs. 2.4%) and skeletal muscle injury (19.3% vs. 4.8%) [52].
T133 19687-19809 Sentence denotes This does not take into account more diffuse symptoms, such as confusion or headache, which may also be neurological [51].
T134 19810-19898 Sentence denotes Most COVID-19 patients seem to exhibit pulmonary symptoms before neurological ones [49].
T135 19899-20125 Sentence denotes About a third of diagnosed COVID-19 patients have some form of symptomology of suspected neurological origin, which might include headache, dizziness, impaired consciousness, ataxia, epilepsy, and cerebrovascular disease [49].
T136 20126-20269 Sentence denotes Besides an impaired or absent sense of smell or taste, vision disturbances, neuralgia, and skeletal muscle damage have also been reported [49].
T137 20270-20473 Sentence denotes Nucleic acid from the SARS-CoV-2 virus has been detected in the cerebrospinal fluid of patients, and the virus itself has been identified in brain tissue on autopsy of patients who died of COVID-19 [49].
T138 20474-20553 Sentence denotes Such findings are rare but confirm that the SARS-CoV-2 virus can enter the CNS.
T139 20554-20783 Sentence denotes A 24-year-old Japanese man with COVID-19 presented with generalized epileptic seizures and decreased consciousness; RNA from the SARS-CoV-2 was not detectable in his nasopharynx but was identified in the cerebrospinal fluid [56].
T140 20784-20962 Sentence denotes Using a polymerase chain reaction (PCR) assay, the SARS-CoV-2 was likewise detected in the cerebrospinal fluid of an obese 40-year-old female COVID-19 patient with diabetes [57].
T141 20964-20988 Sentence denotes Neurotropism in COVID-19
T142 20989-21080 Sentence denotes In general, the distribution of the host’s receptor cells determine viral tropisms [58–60].
T143 21081-21220 Sentence denotes Neurotropism appears to be a common feature of coronaviruses in general, as these viruses share similar viral structures and pathways [50].
T144 21221-21470 Sentence denotes Both SARS-CoV and SARS-CoV-2 enter the body via an ACE-2 receptor-facilitated manner; ACE-2 receptors are highly expressed in the epithelial structures of the airway and vessels, lung parenchyma, the kidney, and cells of the small intestine [61,62].
T145 21471-21723 Sentence denotes Unlike its predecessor, the SARS-CoV, however, the SARS-CoV-2 virus, enters human cells in a process involving dipeptidyl peptidase 4 (DPP4), which is most abundant in the lower respiratory tract, kidney, small intestine, liver, and immune system [63].
T146 21724-21842 Sentence denotes The SARS-CoV virus does not utilize the DPP4 system and is not associated with lower respiratory tract infections [4].
T147 21843-21998 Sentence denotes The expression of ACE-2 receptor cells and DPP4 are very low in the CNS [64], and the route by which coronaviruses enter the CNS is subject to speculation.
T148 21999-22153 Sentence denotes It has been suggested that they invade peripheral nerve terminals first, and, in that way, enter onto a synapse-connected pathway into the CNS [23,65–67].
T149 22154-22314 Sentence denotes This so-called ‘trans-synaptic transfer’ has been observed for other lesser-known coronaviruses, such as HEV67N and the avian bronchitis virus [10,23,65,67,68].
T150 22315-22549 Sentence denotes Indeed, the HEV67N virus has been demonstrated in porcine studies to invade the brain; first, it infects the nasal mucosa, lungs, and small intestines and then peripheral nerves transport it retrogradely to the medullary neurons [66].
T151 22550-22649 Sentence denotes The avian bronchitis virus infects the brainstem of mice and may cause neuroanatomical disruptions.
T152 22650-22778 Sentence denotes The mice that died of respiratory failure may have had failure of the cardiorespiratory center within the brain stem [23,64,69].
T153 22780-22825 Sentence denotes COVID-19 and specific neurological conditions
T154 22826-22968 Sentence denotes Neurological manifestations of COVID-19 may be mild and diffuse, such as headache and myalgia or severe, such as intracranial infections [50].
T155 22969-23091 Sentence denotes While severe neurological symptoms have been reported and are associated with worse outcomes, they appear to be rare [50].
T156 23092-23317 Sentence denotes It is important in this connection to note that COVID-19 may cause specific neurological symptoms, exacerbate preexisting neurological conditions, or unmask preexisting neurological conditions that had not yet been diagnosed.
T157 23318-23444 Sentence denotes Any number of infections can unmask an undiagnosed neurological condition, resulting in their overt emergence or exacerbation.
T158 23445-23610 Sentence denotes Thus, a portion of COVID-associated neurological and neuromuscular symptoms may be unmasked in the pandemic rather than directly caused by the SARS-CoV-2 virus [70].
T159 23611-24204 Sentence denotes In a study from the United Kingdom of 43 patients with a confirmed COVID-19 diagnosis or where the diagnosis of COVID-19 was deemed ‘probable’ or ‘possible’ based on World Health Organization criteria, 10/43 patients had encephalopathy with delirium/psychosis and no abnormalities on magnetic resonance imaging or in cerebrospinal fluid, 12/43 exhibited inflammatory syndromes of the central nervous system, including encephalitis, 8/43 had ischemic stroke, 8/43 had peripheral neurological disorders (predominantly Guillain-Barré syndrome), and 5/43 with miscellaneous central disorders [71].
T160 24205-24300 Sentence denotes These neurological disorders were similar to those associated with other coronavirus epidemics.
T161 24301-24502 Sentence denotes An online network of rapid-response case report notifications in the United Kingdom was launched in April and collected 23 days of data in April 2020 about COVID-19 patients with neurological symptoms.
T162 24503-24568 Sentence denotes A total of 153 cases were reported that met clinical definitions.
T163 24569-24808 Sentence denotes The median patient age was 71 years (range 23–94, interquartile range 58–79) with 62% presenting with a cerebrovascular event, 74% with ischemic stroke, 12% with intracerebral hemorrhage, and 1% with central nervous system vasculitis [72].
T164 24809-25141 Sentence denotes In the ALBACOVID registry study of 841 hospitalized COVID-19 patients in Spain evaluated in March 2020, 57% had some neurological symptom(s), with myalgia, headache, and dizziness more likely to occur early in the diseases; neurological complication were the main cause of death in 4% of the decedents in this study population [73].
T165 25142-25336 Sentence denotes Patients with confirmed or suspected COVID-19 may have preexisting neurological conditions or be at elevated risk for them, for example, patients with atrial fibrillation are at risk for stroke.
T166 25337-25466 Sentence denotes Certain motor neuron diseases, such as amyotrophic lateral sclerosis, may put patients at elevated risk for infection in general.
T167 25467-25621 Sentence denotes Of particular concern are patients with muscular dystrophies associated with weakness of ventilator muscles or cardiomyopathy who are exposed to COVID-19.
T168 25622-25737 Sentence denotes In such cases, patients may recover from COVID-19 but not go back to their baseline neuromuscular functioning [70].
T169 25739-25753 Sentence denotes Encephalopathy
T170 25754-25948 Sentence denotes Encephalopathy, which often presents in infectious disease patients as delirium, is a brain disorder that causes acute or subacute dysfunction in terms of consciousness or altered mental states.
T171 25949-26102 Sentence denotes The elderly, people with cognitive deficits, and people with hypertension are elevated risk for developing an altered mental state with COVID-19 [52,74].
T172 26103-26255 Sentence denotes Cerebral edema, a dangerous condition which can cause elevated intracranial pressure and encephalopathy, has been identified in COVID-19 decedents [75].
T173 26256-26419 Sentence denotes Those with a history of neurological damage and acute respiratory distress are at elevated risk for developing encephalopathy as the initial COVID-19 symptom [76].
T174 26420-26568 Sentence denotes The risk becomes greater as the COVID-19 becomes more severe; altered consciousness occurs in 2.4% of mild and 15% of severe COVID-19 patients [52].
T175 26569-26679 Sentence denotes The risk for delirium, like the risk for worse outcomes with COVID-19, is also associated with older age [77].
T176 26680-26804 Sentence denotes The use of sedatives, which is common in critically ill patients, may also be associated with the risk for delirium [78,79].
T177 26805-27068 Sentence denotes Social distancing mandated for COVID-19 may actually contribute to the rate of delirium of certain COVID-19 patients, who may feel desperate and panicked as they are isolated, separated from family, alone, and/or denied religious support from a clergyperson [77].
T178 27069-27389 Sentence denotes Delirium in hospitalized COVID-19 patients may be the result of direct CNS invasion, induction of CNS inflammatory mediators, a secondary effect of other organ system failures, the effect of sedation, the result of prolonged mechanical ventilation, a psychological manifestation, or caused by environmental factors [77].
T179 27390-27656 Sentence denotes In cases of COVID-19, it is thought that delirium caused by direct invasion of the virus into the CNS is relatively rare, but possible, and would likely be accompanied by seizures, altered states of consciousness, or signs of increased intracranial pressure [39,46].
T180 27657-27757 Sentence denotes The rates and presentation of encephalopathy and delirium in COVID-19 patients has not been studied.
T181 27758-27947 Sentence denotes Delirium in COVID-19 patients may be under-reported to date, indeed delirium is thought to be widely under-reported for various conditions unless it is being specifically monitored [79–82].
T182 27948-28026 Sentence denotes Case studies of COVID-19-associated delirium appear in the literature [83,84].
T183 28027-28151 Sentence denotes Acute necrotizing encephalopathy, although relatively rare, has also been diagnosed in a hospitalized COVID-19 patient [85].
T184 28152-28331 Sentence denotes Overall, ICU patients on mechanical ventilation have rates of delirium as high as 70% to 75%, and delirium is associated with mortality and long-term cognitive impairment [86–88].
T185 28332-28465 Sentence denotes The causes of COVID-19-associated encephalopathy may involve multiple factors, including metabolic causes, hypoxia, and drug therapy.
T186 28466-28559 Sentence denotes Symptomatic treatment involves antipyretics, anticonvulsants, and treatment for hypoxia [21].
T187 28560-28719 Sentence denotes Early signs of delirium in COVID-19 patients might suggest CNS involvement and, as such, might indicate heightened risk for impending respiratory failure [77].
T188 28720-28965 Sentence denotes In a study of 27 pediatric COVID-19 patients with multisystem inflammatory syndrome, 15% (n = 4) exhibited new-onset neurological symptoms, such as encephalopathy, headaches, brainstem, and cerebellar signs, weak muscles, and poor reflexes [89].
T189 28966-29156 Sentence denotes Cerebrospinal fluid testing in two patients were acellular; three patients underwent nerve conduction and electromyographical studies, which revealed mild myopathic and neuropathic deficits.
T190 29157-29256 Sentence denotes All four patients improved, two of whom made a complete recovery over the course of the study [89].
T191 29258-29287 Sentence denotes Guillain-Barré syndrome (GBS)
T192 29288-29368 Sentence denotes GBS typically involves demyelination and presents in both upper and lower limbs.
T193 29369-29547 Sentence denotes While there is no clear evidence to date associating the SARS-CoV-2 virus with GBS, other viral infections, such as influenza and the Epstein-Barr virus, have been linked to GBS.
T194 29548-29717 Sentence denotes The association is based on the idea that there can be molecular mimicry between certain viral proteins and the gangliosides and other proteins on the peripheral nerves.
T195 29718-29831 Sentence denotes This can result in an ‘innocent bystander attack’ against the myelin sheath or axon of the peripheral nerve [70].
T196 29832-30027 Sentence denotes GBS is a complex disorder and has been recognized as a para-infectious neurological disease, and has associations with the Zika virus that were documented during the 2015–2016 Zika epidemic [90].
T197 30028-30097 Sentence denotes It is not known if the coronavirus can damage peripheral nerves [44].
T198 30098-30450 Sentence denotes The literature reports on several cases that suggest a link between COVID-19 and GBS [91–94], for example, the case of a 62-year-old COVID patient with GBS; however it is unclear if this patient, who had comorbid lymphopenia and thrombocytopenia, developed GBS and COVID-19 independently but concurrently, or if COVID-19 might have caused the GBS [95].
T199 30451-30574 Sentence denotes It must likewise be considered that COVID-19-associated neurological manifestations may emerge after the initial infection.
T200 30575-30693 Sentence denotes Thus, while there is currently no evidence that COVID-19 can cause GBS, it is an area worthy of further investigation.
T201 30694-30923 Sentence denotes It should be noted in this context that clinicians may sometimes observe peripheral neuropathies, for example based around the ulna, that have to do with prolonged intubation periods in a position that impinges the cubital canal.
T202 30925-30961 Sentence denotes Myopathy and neuromuscular disorders
T203 30962-31159 Sentence denotes Myalgia and fatigue are common symptoms of COVID-19 and a study of COVID-19 patients found 44% to 70% of hospitalized patients had these symptoms and 33% had increased creatine kinase (CK) [10,96].
T204 31160-31387 Sentence denotes However, the nature of the rapid outbreak and spread of the virus did not allow for thorough workup of such COVID-19 patients that might have included electromyography testing, muscle imaging, or histopathological examinations.
T205 31388-31498 Sentence denotes Myalgia occurred in about a third of SARS patients [97], and rhabdomyolysis has been observed as well [47,98].
T206 31500-31512 Sentence denotes Encephalitis
T207 31513-31590 Sentence denotes Encephalitis or inflammation of the brain may be caused by a viral infection.
T208 31591-31703 Sentence denotes The symptoms of encephalitis include fever, headache, seizures, altered consciousness, and behavioral disorders.
T209 31704-31844 Sentence denotes A case report from China describes encephalitis in a male patient with COVID-19 with no traces of the SARS-CoV-2 in his cerebrospinal fluid.
T210 31845-31991 Sentence denotes His main symptom was altered consciousness but the condition was self-limiting and the patient recovered from both COVID-19 and encephalitis [99].
T211 31992-32113 Sentence denotes Although unusual, patients with COVID-19 may present with encephalitis rather than the typical respiratory symptoms [57].
T212 32114-32179 Sentence denotes COVID-19 patients with encephalitis may also experience seizures.
T213 32180-32291 Sentence denotes In particular, it is important to note that nonconvulsive status epilepticus (NCSE) may occur in such patients.
T214 32292-32484 Sentence denotes The Salzburg Consensus Criteria for Nonconvulsive Status Epilepticus was published in 2015 and provides terminology definitions and identified specific EEG tracings associated with NCSE [100].
T215 32485-32636 Sentence denotes NCSE may be evident on electroencephalography (EEG), so that continuous EEG monitoring may be appropriate for critically ill patients in general [101].
T216 32637-32706 Sentence denotes In comatose patients, NCSE has a prevalence between 5% and 48% [102].
T217 32707-32769 Sentence denotes Its prevalence specifically in COVID-19 patients is not known.
T218 32771-32789 Sentence denotes Cephalgia/headache
T219 32790-32982 Sentence denotes Early reports out of Wuhan described headache and decreased responsiveness of patients as an early indicator of potential neurologic involvement associated with the SARS-CoV-2 infection [103].
T220 32983-33066 Sentence denotes Headaches have been reported in 11% to 34% of hospitalized COVID-19 patients [104].
T221 33067-33213 Sentence denotes Among COVID-19 patients who developed symptoms, the incidence of headache is 6% to 10% and headache was often among the presenting symptoms [104].
T222 33214-33391 Sentence denotes Initial reports of the so-called ‘COVID-19 headache’ describe bilateral cephalgia characterized by pulsating pain in the temporoparietal region, forehead, or periorbital region.
T223 33392-33506 Sentence denotes Such headaches were limited to active periods of the COVID-19 infection and resisted conventional analgesia [104].
T224 33507-33661 Sentence denotes While it is plausible that these headaches relate to the viral invasion, they may also be a byproduct of cytokine storm or have some other etiology [105].
T225 33663-33700 Sentence denotes Critical-illness polyneuropathy (CIP)
T226 33701-33788 Sentence denotes Acute neuropathy or CIP may develop in patients suffering a number of severe illnesses.
T227 33789-33856 Sentence denotes CIP typically remits as the patient recovers from the illness [44].
T228 33857-34126 Sentence denotes Signs and symptoms of CIP include reduced compound muscle action potentials amplitude, abnormal spontaneous unilateral activities in the diaphragmatic needle electromyography evaluation, abnormal F responses, and an abnormal H reflex on electrodiagnostic studies [106].
T229 34127-34263 Sentence denotes The pathogenesis of CIP is not well elucidated and may involve a systemic inflammatory response to sepsis that damages the nerves [107].
T230 34264-34316 Sentence denotes Its prevalence among COVID-19 patients is not known.
T231 34318-34344 Sentence denotes Cerebrovascular conditions
T232 34345-34434 Sentence denotes Vascular comorbidities seem to pose a risk factor for worse outcomes with COVID-19 [108].
T233 34435-34518 Sentence denotes Stroke is emerging as an increasingly important adverse event in COVID-19 patients.
T234 34519-34845 Sentence denotes From a retrospective single-center study in China (n = 221), risk factors for stroke in COVID-19 patients appear to be: older age, more severe COVID-19, history of hypertension, diabetes, cerebrovascular diseases, and any marked inflammatory or pro-coagulant response, such as a high C-reactive protein or D-dimer level [108].
T235 34846-34936 Sentence denotes Cerebrovascular conditions may present as neurological symptoms in COVID-19 patients [21].
T236 34938-34985 Sentence denotes Parkinson’s disease (PD) and movement disorders
T237 34986-35169 Sentence denotes The etiology of PD likely involves the interplay of genetic and environmental factors, but viruses have been implicated in causing parkinsonism and other movement disorders [109,110].
T238 35170-35517 Sentence denotes In a study using the cerebrospinal fluid of 67 patients (20 with PD, 29 without PD but with another neurological disorder, and 18 healthy controls), the PD patients had a significantly higher mean cerebrospinal fluid antibody response to two specific coronaviruses (MHV-JHM and MHV-A59) than controls or patients with other neurological disorders.
T239 35518-35634 Sentence denotes It was theorized that some strain of coronavirus might contribute over the long term to the development of PD [110].
T240 35635-35864 Sentence denotes This may relate to the epidemiological observation that people who live on farms or grow up in farming communities have a higher risk of developing PD than others, possible due to zoonotic transmission of coronaviruses [111,112].
T241 35865-36035 Sentence denotes There is no compelling evidence to suggest that patients with PD are more likely to contract COVID-19 or that they are at elevated risk for worse COVID-19 outcomes [113].
T242 36036-36200 Sentence denotes However, PD is associated with decreased respiratory function, which might contribute to respiratory distress in any number of infections, including COVID-19 [114].
T243 36201-36418 Sentence denotes Furthermore, PD is comorbid with a number of disorders, including cerebrovascular disease, heart failure, and coronary artery disease, any of which would elevate risk of worse outcomes if COVID-19 was contracted [22].
T244 36420-36440 Sentence denotes Pulmonary conditions
T245 36441-36661 Sentence denotes It has been postulated that the neuroinvasion of the brain’s medulla oblongata region by the SARS-CoV-2 virus might impair cardiorespiratory control centers and, in that way, lead to respiratory distress and failure [4].
T246 36662-36789 Sentence denotes The literature reports a COVID-19 patient who lost the involuntary process of breathing and suffered respiratory failure [115].
T247 36790-36931 Sentence denotes ACE-2 receptors are expressed abundantly in the body, even in the brain, and particularly in the brain stem which controls respiration [116].
T248 36932-37084 Sentence denotes In the event that the SARS-CoV-2 virus might enter the microcirculatory system of the brain, it may access ACE-2 receptors in the capillary endothelium.
T249 37085-37214 Sentence denotes In such a situation, the virus can cause damage to the endothelium itself, enter the brain, and cause neuronal destruction [116].
T250 37215-37392 Sentence denotes Better understanding is urgently needed to elucidate the role of the SARS-CoV-2 virus in the brain and to risk-stratify patients who may be suffering COVID-related brain damage.
T251 37394-37459 Sentence denotes Clinical management of neurological symptoms in COVID-19 patients
T252 37460-37718 Sentence denotes Symptoms frequently reported by COVID-19 patients, such as headache, dizziness, nausea, vomiting, confusion, and fatigue may be neurological, or they may actually be manifestations of hypoxia, respiratory distress, metabolic acidosis, or drug reactions [84].
T253 37719-37899 Sentence denotes Such generalized symptoms occur with many types of infections, can be vague and diffuse, and may be difficult for the patient to associate specifically with the COVID-19 infection.
T254 37900-38046 Sentence denotes Thus, many neurological manifestations of COVID-19 are overlooked, particularly in a pandemic situation when healthcare resources are overwhelmed.
T255 38047-38151 Sentence denotes For that reason, it is important to consider neurological assessments of hospitalized COVID-19 patients.
T256 38152-38264 Sentence denotes Serum urea, creatinine, electrolyte, and blood gas tests may be helpful to indicate if there is CNS involvement.
T257 38265-38398 Sentence denotes The loss of smell and/or taste early in the course of the disease may be significant and point toward neurological involvement [117].
T258 38399-38659 Sentence denotes Alterations to the senses of taste and smell have been reported in early-stage COVID-19 cases without complications and suggest that the virus is moving toward the olfactory bulb of the brain, which would permit it to enter and possibly affect the brain [118].
T259 38660-38798 Sentence denotes However, it must be noted that anosmia and ageusia can also be reported in the setting of non-COVID-19 upper respiratory tract infections.
T260 38799-38935 Sentence denotes Treating neurological symptoms can be challenging as drugs that suppress the immune system may be contraindicated for COVID-19 patients.
T261 38936-39023 Sentence denotes There is evidence that the use of corticosteroids may prolong viral shedding [119,120].
T262 39024-39346 Sentence denotes Symptoms for neurological problems may be addressed, with first-line strategies such as controlling body temperature, offering anticonvulsants, and treating hypoxia.21 Second-line treatments for neuroinflammation involve IV immunoglobulin or plasma exchange, but IV immunoglobulin may increase the risk of thromboembolism.
T263 39347-39451 Sentence denotes Furthermore, there is emerging concern of the possibility of microthrombosis in COVID-19 patients [121].
T264 39452-39618 Sentence denotes Third-line strategies for neuroinflammation in COVID patients may carry higher risks, and include such pharmacological agents as cyclophosphamide and rituximab [121].
T265 39619-39770 Sentence denotes Typically, COVID-19 patients present with respiratory symptoms before neurological ones, but atypical presentations, although rare, have been reported.
T266 39771-39977 Sentence denotes When neurological symptoms are present in suspected COVID-19 patients, it may be important to test and, if necessary, treat them for COVID-19 first and then address the neurological disorder afterward [49].
T267 39978-40132 Sentence denotes Although not yet fully characterized, neurological symptoms related to COVID-19 are thought to be possible following resolution of the COVID-19 infection.
T268 40133-40401 Sentence denotes In the hospital, distinct and separate areas for neurological emergencies versus COVID-related emergencies may be helpful in order to preclude that a patient with a neurological emergency but not COVID-19 does not come inadvertently in contact with a COVID-19 patient.
T269 40402-40614 Sentence denotes When treating patients with neurological symptoms but no confirmed COVID-19 diagnosis, physicians, and other clinicians should ask about fever, sore throat, exposure history in the past two weeks, and so on [49].
T270 40615-40712 Sentence denotes Testing is important, particularly if there is any reason to suspect possible COVID-19 infection.
T271 40713-40890 Sentence denotes COVID-19 patients who have suffered neurological complications, including stroke, may require acute rehabilitation or, in some cases, long-term residential-skilled nursing care.
T272 40891-41195 Sentence denotes Some patients who undergo prolonged hospitalization with extended periods prone in bed during mechanical ventilation may present following hospitalization with myopathy or neuropathy following acute respiratory distress syndrome, possibly necessitating extracorporeal membrane oxygenation (ECMO) therapy.
T273 41196-41320 Sentence denotes Other presentations may include reversible posterior encephalopathy or the sequela of severe stroke of a large blood vessel.
T274 41321-41565 Sentence denotes Weakness acquired through prolonged stays in intensive care, critical-illness polymyopathy, or polyneuropathy can occur with acute respiratory distress syndrome and may require a multidisciplinary approach for rehabilitation and recovery [122].
T275 41567-41577 Sentence denotes Discussion
T276 41578-41814 Sentence denotes As scientists and clinicians concentrate on the complexities of the SARS-CoV-2 virus and better treatment strategies for COVID-19, it is possible that neurological manifestations of COVID-19 are being overlooked or misinterpreted [117].
T277 41815-42091 Sentence denotes In general, neurological symptoms can be under-diagnosed or even entirely overlooked as neurological manifestations, such as delirium in the critically ill COVID-19 patients or infected outpatients who do not consider a loss of the sense of smell or taste related to COVID-19.
T278 42092-42228 Sentence denotes As such, clinicians on the front lines of COVID-19 care should be cognizant of possible neurological manifestations of this novel virus.
T279 42229-42414 Sentence denotes Patients with suspected or diagnosed COVID-19 should be asked about the loss of smell and taste and educated that this is an important symptom to bring to the attention of the provider.
T280 42415-42521 Sentence denotes Neurological symptoms of COVID-19 have to date mainly be described within the trajectory of the infection.
T281 42522-42734 Sentence denotes However, it is plausible (although far from established) that neurological sequelae from COVID-19 may emerge after the patient has recovered from the primary infection and persist for long periods after recovery.
T282 42735-42899 Sentence denotes For example, it is not known if an elderly patient who recovers from a severe case of COVID-19 with cognitive dysfunction will suffer persistent cognitive deficits.
T283 42900-43160 Sentence denotes The long-term burden on both caregivers and the healthcare system that might be posed by COVID-19 survivors with neurological or cognitive impairment may turn out to be very important, although it is one that is rarely discussed, even hypothetically [123,124].
T284 43161-43305 Sentence denotes There is evidence of neurological complications with SARS and MERS, and a growing body of evidence for neurological complications with COVID-19.
T285 43306-43584 Sentence denotes The etiology of these neurological symptoms is less clear; they may be directly caused by the viral infection or they could be due to other conditions, such as sepsis, coagulation disorders, cytokine release, and vasculitis, all of which have been reported in COVID-19 patients.
T286 43585-43729 Sentence denotes Much more needs to be learned, but clinicians must be aware and prepared for the possibility and potentiality of COVID-19 neurological symptoms.
T287 43730-43793 Sentence denotes The evidence that the SARS-CoV-2 can enter the CNS is alarming.
T288 43794-43952 Sentence denotes While autopsy studies show definitive proof that the earlier SARS-CoV was found in brain tissue, viral levels were lower in the brain than in the lungs [125].
T289 43953-44059 Sentence denotes The route by which the SARS-CoV-2 virus enters the CNS and its effects on the CNS remain to be elucidated.
T290 44060-44152 Sentence denotes It is important to learn more about chronic neurological complications related to COVID-019.
T291 44153-44335 Sentence denotes The blood-brain barrier, which may protect patients from invading pathogens, is a two-way street and could in theory at least prevent viruses from being expelled from the brain [50].
T292 44336-44489 Sentence denotes Further study is needed, particularly as the population of COVID-recovered patients grows and may have to manage long-term consequences of the infection.
T293 44491-44502 Sentence denotes Limitations
T294 44503-44571 Sentence denotes COVID-19 is a complex condition that has yet to be fully elucidated.
T295 44572-44690 Sentence denotes New information appears daily in the medical literature and some earlier concepts about the disease have been revised.
T296 44691-44826 Sentence denotes This article was produced during the pandemic and may reflect an incomplete understanding of the neurological consequences of COVID-19.
T297 44828-44838 Sentence denotes Conclusion
T298 44839-45077 Sentence denotes Neurological impairment has been reported with the coronaviruses related to the earlier SARS and MERS epidemics, and there is growing awareness of what may be potentially serious neurological effects of the virus associated with COVID-19.
T299 45078-45229 Sentence denotes While most COVID-19 patients develop respiratory symptoms prior to or to the exclusion of neurological symptoms, atypical COVID-19 cases have occurred.
T300 45230-45399 Sentence denotes Neurological symptoms may be mild, such as headache, dizziness, or altered consciousness or may include encephalitis, which might also be the result of critical illness.
T301 45400-45516 Sentence denotes The link between neurological involvement and respiratory failure has been suspected but remains to be investigated.
T302 45517-45587 Sentence denotes Clinicians should be aware of neurological symptoms in their patients.
T303 45589-45604 Sentence denotes Acknowledgments
T304 45605-45759 Sentence denotes This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
T305 45760-45845 Sentence denotes No funding or sponsorship was received for this study or publication of this article.
T306 45847-45870 Sentence denotes Declaration of interest
T307 45871-45955 Sentence denotes None of the authors has any relevant financial disclosures or conflicts of interest.
T308 45957-46001 Sentence denotes Declaration of financial/other relationships
T309 46002-46067 Sentence denotes The other authors on the manuscript have no relevant disclosures.