Id |
Subject |
Object |
Predicate |
Lexical cue |
T153 |
0-45 |
Sentence |
denotes |
COVID-19 and specific neurological conditions |
T154 |
46-188 |
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 |
189-311 |
Sentence |
denotes |
While severe neurological symptoms have been reported and are associated with worse outcomes, they appear to be rare [50]. |
T156 |
312-537 |
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 |
538-664 |
Sentence |
denotes |
Any number of infections can unmask an undiagnosed neurological condition, resulting in their overt emergence or exacerbation. |
T158 |
665-830 |
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 |
831-1424 |
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 |
1425-1520 |
Sentence |
denotes |
These neurological disorders were similar to those associated with other coronavirus epidemics. |
T161 |
1521-1722 |
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 |
1723-1788 |
Sentence |
denotes |
A total of 153 cases were reported that met clinical definitions. |
T163 |
1789-2028 |
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 |
2029-2361 |
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 |
2362-2556 |
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 |
2557-2686 |
Sentence |
denotes |
Certain motor neuron diseases, such as amyotrophic lateral sclerosis, may put patients at elevated risk for infection in general. |
T167 |
2687-2841 |
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 |
2842-2957 |
Sentence |
denotes |
In such cases, patients may recover from COVID-19 but not go back to their baseline neuromuscular functioning [70]. |
T169 |
2959-2973 |
Sentence |
denotes |
Encephalopathy |
T170 |
2974-3168 |
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 |
3169-3322 |
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 |
3323-3475 |
Sentence |
denotes |
Cerebral edema, a dangerous condition which can cause elevated intracranial pressure and encephalopathy, has been identified in COVID-19 decedents [75]. |
T173 |
3476-3639 |
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 |
3640-3788 |
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 |
3789-3899 |
Sentence |
denotes |
The risk for delirium, like the risk for worse outcomes with COVID-19, is also associated with older age [77]. |
T176 |
3900-4024 |
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 |
4025-4288 |
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 |
4289-4609 |
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 |
4610-4876 |
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 |
4877-4977 |
Sentence |
denotes |
The rates and presentation of encephalopathy and delirium in COVID-19 patients has not been studied. |
T181 |
4978-5167 |
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 |
5168-5246 |
Sentence |
denotes |
Case studies of COVID-19-associated delirium appear in the literature [83,84]. |
T183 |
5247-5371 |
Sentence |
denotes |
Acute necrotizing encephalopathy, although relatively rare, has also been diagnosed in a hospitalized COVID-19 patient [85]. |
T184 |
5372-5551 |
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 |
5552-5685 |
Sentence |
denotes |
The causes of COVID-19-associated encephalopathy may involve multiple factors, including metabolic causes, hypoxia, and drug therapy. |
T186 |
5686-5779 |
Sentence |
denotes |
Symptomatic treatment involves antipyretics, anticonvulsants, and treatment for hypoxia [21]. |
T187 |
5780-5939 |
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 |
5940-6185 |
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 |
6186-6376 |
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 |
6377-6476 |
Sentence |
denotes |
All four patients improved, two of whom made a complete recovery over the course of the study [89]. |
T191 |
6478-6507 |
Sentence |
denotes |
Guillain-Barré syndrome (GBS) |
T192 |
6508-6588 |
Sentence |
denotes |
GBS typically involves demyelination and presents in both upper and lower limbs. |
T193 |
6589-6767 |
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 |
6768-6937 |
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 |
6938-7051 |
Sentence |
denotes |
This can result in an ‘innocent bystander attack’ against the myelin sheath or axon of the peripheral nerve [70]. |
T196 |
7052-7247 |
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 |
7248-7317 |
Sentence |
denotes |
It is not known if the coronavirus can damage peripheral nerves [44]. |
T198 |
7318-7670 |
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 |
7671-7794 |
Sentence |
denotes |
It must likewise be considered that COVID-19-associated neurological manifestations may emerge after the initial infection. |
T200 |
7795-7913 |
Sentence |
denotes |
Thus, while there is currently no evidence that COVID-19 can cause GBS, it is an area worthy of further investigation. |
T201 |
7914-8143 |
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 |
8145-8181 |
Sentence |
denotes |
Myopathy and neuromuscular disorders |
T203 |
8182-8379 |
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 |
8380-8607 |
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 |
8608-8718 |
Sentence |
denotes |
Myalgia occurred in about a third of SARS patients [97], and rhabdomyolysis has been observed as well [47,98]. |
T206 |
8720-8732 |
Sentence |
denotes |
Encephalitis |
T207 |
8733-8810 |
Sentence |
denotes |
Encephalitis or inflammation of the brain may be caused by a viral infection. |
T208 |
8811-8923 |
Sentence |
denotes |
The symptoms of encephalitis include fever, headache, seizures, altered consciousness, and behavioral disorders. |
T209 |
8924-9064 |
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 |
9065-9211 |
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 |
9212-9333 |
Sentence |
denotes |
Although unusual, patients with COVID-19 may present with encephalitis rather than the typical respiratory symptoms [57]. |
T212 |
9334-9399 |
Sentence |
denotes |
COVID-19 patients with encephalitis may also experience seizures. |
T213 |
9400-9511 |
Sentence |
denotes |
In particular, it is important to note that nonconvulsive status epilepticus (NCSE) may occur in such patients. |
T214 |
9512-9704 |
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 |
9705-9856 |
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 |
9857-9926 |
Sentence |
denotes |
In comatose patients, NCSE has a prevalence between 5% and 48% [102]. |
T217 |
9927-9989 |
Sentence |
denotes |
Its prevalence specifically in COVID-19 patients is not known. |
T218 |
9991-10009 |
Sentence |
denotes |
Cephalgia/headache |
T219 |
10010-10202 |
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 |
10203-10286 |
Sentence |
denotes |
Headaches have been reported in 11% to 34% of hospitalized COVID-19 patients [104]. |
T221 |
10287-10433 |
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 |
10434-10611 |
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 |
10612-10726 |
Sentence |
denotes |
Such headaches were limited to active periods of the COVID-19 infection and resisted conventional analgesia [104]. |
T224 |
10727-10881 |
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 |
10883-10920 |
Sentence |
denotes |
Critical-illness polyneuropathy (CIP) |
T226 |
10921-11008 |
Sentence |
denotes |
Acute neuropathy or CIP may develop in patients suffering a number of severe illnesses. |
T227 |
11009-11076 |
Sentence |
denotes |
CIP typically remits as the patient recovers from the illness [44]. |
T228 |
11077-11346 |
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 |
11347-11483 |
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 |
11484-11536 |
Sentence |
denotes |
Its prevalence among COVID-19 patients is not known. |
T231 |
11538-11564 |
Sentence |
denotes |
Cerebrovascular conditions |
T232 |
11565-11654 |
Sentence |
denotes |
Vascular comorbidities seem to pose a risk factor for worse outcomes with COVID-19 [108]. |
T233 |
11655-11738 |
Sentence |
denotes |
Stroke is emerging as an increasingly important adverse event in COVID-19 patients. |
T234 |
11739-12065 |
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 |
12066-12156 |
Sentence |
denotes |
Cerebrovascular conditions may present as neurological symptoms in COVID-19 patients [21]. |
T236 |
12158-12205 |
Sentence |
denotes |
Parkinson’s disease (PD) and movement disorders |
T237 |
12206-12389 |
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 |
12390-12737 |
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 |
12738-12854 |
Sentence |
denotes |
It was theorized that some strain of coronavirus might contribute over the long term to the development of PD [110]. |
T240 |
12855-13084 |
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 |
13085-13255 |
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 |
13256-13420 |
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 |
13421-13638 |
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 |
13640-13660 |
Sentence |
denotes |
Pulmonary conditions |
T245 |
13661-13881 |
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 |
13882-14009 |
Sentence |
denotes |
The literature reports a COVID-19 patient who lost the involuntary process of breathing and suffered respiratory failure [115]. |
T247 |
14010-14151 |
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 |
14152-14304 |
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 |
14305-14434 |
Sentence |
denotes |
In such a situation, the virus can cause damage to the endothelium itself, enter the brain, and cause neuronal destruction [116]. |
T250 |
14435-14612 |
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. |