No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Risk Factors for New Neurologic Diagnoses in Hospitalized Patients with COVID-19: A Case-Control Study in New York City
Abstract
Background/Objective: There have been numerous reports of neurological manifestations identified in hospitalized patients infected with SARS-CoV-2, the virus that causes COVID-19. Here, we identify the spectrum of associated neurological symptoms and diagnoses, define the time course of their development, examine readmission rates and mortality risk post-hospitalization in a multiethnic urban cohort.
Methods: We identify the occurrence of new neurological diagnoses among patients with laboratory-confirmed SARS-CoV-2 infection in New York City. A retrospective cohort study was performed of 532 cases (hospitalized patients with new neurological diagnoses within 6 weeks of positive SARS-CoV-2 laboratory results between March 1, 2020 and August 31, 2020). We compare demographic and clinical features of the 532 cases to 532 COVID-19 positive controls without neurological diagnoses in a case-control study with 1 to 1 matching; and examine hospital-related data and outcomes of death and readmission up to 6 months after acute hospitalization in a secondary case-only analysis.
Results: Among the 532 cases, the most common new neurological diagnoses included encephalopathy (478, 89.8%), stroke (66, 12.4%), and seizures (38, 7.1%). In the case-control study, cases were more likely than controls to be male (58.6% vs. 52.8%, p=0.05), have baseline neurological comorbidities (36.3% vs. 13.0%, p<0.0001) and be treated in an intensive care unit (ICU) (62.0% vs. 9.6%, p < 0.0001). Of the 394 (74.1%) cases that survived the acute hospitalization, more than half (220/394, 55.8%) were readmitted within 6 months, with a mortality rate of 23.2% during readmission.
Conclusion: Many patients hospitalized with SARS-CoV-2 have new neurological diagnoses, with significant morbidity and mortality post-discharge. Further research is needed to define the impact of neurological diagnoses during acute hospitalization on longitudinal post-COVID-19 related symptoms including neurocognitive impairment.
... In December 2019, patients in the Wuhan province of China were diagnosed with an unexplained pneumonia that was found to be caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) [5]. Reports from epicenters of the resultant pandemic, including China [6], Italy [7,8], the United Kingdom [9][10][11][12], France [13][14][15][16], Spain [17][18][19], and the United States [20][21][22][23][24][25][26][27][28][29], have described neuropsychiatric manifestations of this novel coronavirus disease 2019 (COVID-19, or simply COVID), ranging from hyposmia/ hypogeusia, headache, dizziness, and critical illness neuropathy/myopathy to alteration of consciousness, seizure, central nervous system (CNS) infection, acute inflammatory demyelinating polyneuropathy, and acute cerebrovascular disease [30][31][32][33][34]. Neuropsychiatric complications can only compound morbidity, complicate recovery, and increase mortality, so their recognition is valuable to understanding of the impact of the COVID pandemic. ...
... A retrospective study of 4711 SARS-CoV-2-positive patients at four hospitals within Montefiore Health System reported a prevalence of neurological complications in 12%, with altered mentation in 5.5%, stroke in 1.2%, and seizures in 0.7% [26]. Within the NewYork-Presbyterian Hospital system, one single-center retrospective case-control study [28] identified 532 incident cases of COVID-19-associated neurological diagnoses, of which the most common were encephalopathy (89.8%), stroke (12.4%), and seizures (7.1%), while a retrospective study of 282 COVID-19-positive patients who had neurology consultation at another hospital within the system [25] identified 56 with neurological symptoms on presentation (impaired consciousness in 45%, ischemic stroke in 32%, headache in 13%, and seizure in 11%). Overall, these studies, performed largely at private academic hospitals, reported higher estimates of neurological complications compared to a retrospective cohort of 5,455 patients at four public teaching hospitals within the New York Health + Hospitals system, which reported a 5.2% prevalence of neurological complications, with predominant symptoms of headache (1.5%), seizure (1.3%), stroke (1.2%), and alteration of consciousness (0.2%) [29]. ...
... Notably, treatment with anticoagulant and antiviral therapy was associated with lower odds of altered mental status. The prevalence of seizures, ischemic and hemorrhagic stroke, and CNS infection/inflammation were less common, but broadly comparable to estimates reported by other studies from New York City centers, and peripheral nervous system complications were diagnosed less frequently than CNS complications, which may have been due to decreased utilization of electrodiagnostic studies during the pandemic [23,28,29]. Our findings extend those of prior reports Content courtesy of Springer Nature, terms of use apply. ...
Objective
To describe the frequency of neuropsychiatric complications among hospitalized patients with coronavirus disease 2019 (COVID-19) and their association with pre-existing comorbidities and clinical outcomes.
Methods
We retrospectively identified all patients hospitalized with COVID-19 within a large multicenter New York City health system between March 15, 2020 and May 17, 2021 and randomly selected a representative cohort for detailed chart review. Clinical data, including the occurrence of neuropsychiatric complications (categorized as either altered mental status [AMS] or other neuropsychiatric complications) and in-hospital mortality, were extracted using an electronic medical record database and individual chart review. Associations between neuropsychiatric complications, comorbidities, laboratory findings, and in-hospital mortality were assessed using multivariate logistic regression.
Results
Our study cohort consisted of 974 patients, the majority were admitted during the first wave of the pandemic. Patients were treated with anticoagulation (88.4%), glucocorticoids (24.8%), and remdesivir (10.5%); 18.6% experienced severe COVID-19 pneumonia (evidenced by ventilator requirement). Neuropsychiatric complications occurred in 58.8% of patients; 39.8% experienced AMS; and 19.0% experienced at least one other complication (seizures in 1.4%, ischemic stroke in 1.6%, hemorrhagic stroke in 1.0%) or symptom (headache in 11.4%, anxiety in 6.8%, ataxia in 6.3%). Higher odds of mortality, which occurred in 22.0%, were associated with AMS, ventilator support, increasing age, and higher serum inflammatory marker levels. Anticoagulant therapy was associated with lower odds of mortality and AMS.
Conclusion
Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.
... Neurologic involvement of COVID-19 infections manifests as a worsening of underlying neurological disorders, development of new neurological symptoms, or postinfectious sequelae. [19][20][21] While the acute neurological complications of those hospitalized with the original strain of SARS-CoV-2 have been extensively studied, few have explored the degree and variety of neurological presentations during the initial Omicron B. ...
... Potential cases were identified from daily review of neurological admissions and CUIMC COVID-CARES database to include hospitalized patients with positive SARS-CoV-2 RT-PCR results admitted to CUIMC-NYP, CHONY-NYP, and Allen-NYP. 19 Following the epidemiological curve of the Omicron B.1.1.529 surge in New York City, daily prospective review of potential cases began January 13, 2022, and ended February 28, 2022. ...
... As reported by Thakur et al., the neurological cases were defined by the same inclusion criteria: diagnosis of select neurological conditions during the acute COVID-19 hospitalization within 6 weeks of a positive SARS-CoV-2 RT-PCR test. 19 This cohort of cases from the first SARS-CoV-2 surge during March -August 2020 will be referred to as group C. The cohort of cases identified during the study period corresponding with the first Omicron variant (B.1.1.529) surge during December 2021 -February 2022 will be referred to as group O. ...
Objective:
Emerging variants and sublineages of SARS-CoV-2 have differing disease severity, transmissibility, and immune evasion. The neurological conditions associated with the original strain of SARS-CoV-2 are well established. Our study assessed the neurological presentations specific to hospitalized patients during the B.1.1.529 (Omicron) variant surge in New York City.
Methods:
A total of 178 cases with positive RT-PCR result within 6 weeks before admission, and subsequent development of select neurological conditions during the SARS-CoV-2 B.1.1.529 (Omicron) surge between December 1, 2021 and February 28, 2022, were included from 12,800 SARS-CoV-2-positive hospital admissions. Clinical data from acute hospitalizations were compared to findings of inpatient neurological cases with COVID-19 infections from the initial surge in NYC in the same hospital system.
Results:
Compared to SARS-CoV-2 infections of the original strain, COVID-19 cases hospitalized during the Omicron surge (B.1.1.529) were associated with incidental and/or asymptomatic COVID-19 cases (96, 53.9%) and an increased incidence of pre-existing neurological and immunocompromising conditions. Encephalopathy, seizures, and stroke remained the most prevalent neurological conditions identified in hospitalized COVID-19 cases during the study period, reflecting a similar distribution of neurological presentations associated with the original strain.
Interpretation:
In our cohort of 178 admitted SARS-CoV-2-positive patients with select neurological conditions during the Omicron B.1.1.529 surge, 54% of COVID-19 cases were considered incidental and/or asymptomatic, and the identified neurological conditions resembled those associated with the original SARS-CoV-2 strain. Further studies characterizing neurological presentation in Omicron sublineages and other variants are warranted in an ongoing COVID-19 pandemic.
... The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the central, peripheral, and neuromuscular nervous systems at any stage of coronavirus disease-2019 (COVID-19) 1 . The neuropathological characteristics of SARS-CoV-2, such as neuro-invasiveness and neuro-virulence 2 , or the dysregulation of immunomodulation 3 could cause neurological manifestations in approximately 78% of hospitalized patients with COVID-19 4,5 . Severe cases of COVID-19 may also present thrombotic 6 , hyperinflammatory and autoimmune processes 7 , or those related to respiratory failure 8 , which can affect the nervous system. ...
... Neurological manifestations or complications in patients with COVID-19 are associated with adverse clinical outcomes 5,14,15 , increased morbidity, and mortality, independent of respiratory disease severity 16 . Otherwise, other studies have identified headache as an independent predictor of lower mortality risk in hospitalized patients with COVID-19 17 . ...
Background: Most of hospitalized patients with COVID-19 have had neurological
manifestations. However, biomarkers for specific neurological manifestations and how these affect clinical outcomes are still unclear. Objective: To describe the frequency of neurological manifestations in patients hospitalized with COVID-19 and analyze their relationship with biomarkers and relevant clinical outcomes. Methods: This retrospective cohort study included adult patients hospitalized due to COVID-19 with at least one neurological manifestation. Headache, anosmia, ageusia, and polyneuromyopathy were classified as nonspecific neurological manifestations, whereas epileptic seizures, decreased level of consciousness, delirium, encephalitis, abnormal movements, ataxia, and cerebrovascular events as specific. Assessed associations: a) clinical and laboratory covariates with the presentation of a specific neurological manifestation; b) the relationship between specific neurological manifestation and COVID-19 severity, mechanical ventilation, and mortality; and c) duration of mechanical ventilation and polyneuromyopathy. Results: Of the 338 patients included in the study, 61,2% had severe COVID-19, 25,2% required mechanical ventilation, and 23,7% died. The most frequent neurological manifestations were headache (68,3%), delirium (41,9%), decreased level
of consciousness (40,8%), and polyneuromyopathy (21,8%). High serum D-dimer levels and lymphopenia were associated with a specific neurological manifestation. At least one specific neurological manifestation was found in 39,9% of patients, and these group was associated with mechanical ventilation and mortality. Finally, a longer duration on mechanical ventilation was associated with a higher frequency of polyneuromyopathy.
Conclusion: Specific neurological manifestations were frequent in hospitalized patients with COVID-19 and are associated with greater clinical and laboratory severity.
... 38 Additionally, hospitalized patients with COVID-19 were more likely to develop neurological conditions, such as encephalopathy, if they were older and had a previous comorbid neurological condition. 39 Thus, the development of neurological complications related to SARS-CoV2 infection might be facilitated by an already compromised blood brain barrier, neuronal dysfunction, or preexisting cerebral atrophy-though more studies are needed to identify causality. These factors are exacerbated by the fact that during the pandemic, the accessibility and availability of CT scan for diagnosis was scarce. ...
Background: In this COVID-19 Critical Care Consortium (CCCC) sub-study, we qualified neurological complications associated with SARS-CoV2 infection.
Methods: The CCCC is an international, multicenter study. Eligible patients were COVID-19 patients admitted to intensive care units (ICU) across 23 centers between 1/7/2020 to 6/23/2022. Incidence of neurological complications was estimated as number of events per hospital days and per admission using Poisson regression. Associations between neurological complications and risk factors were assessed using multivariable Poisson regression.
Results713 patients were included. Median age = 56 years (interquartile range (IQR) = 45-65). Neurological complications reported in 61/480 patients (12.7%) with the majority being ischemic stroke (2.9%), intracranial hemorrhage (ICH) (2.8%), and seizures (2.6%). Multivariable analysis for neurological complications per admitted days showed comorbid neurological conditions (incidence rate ratio (IRR) = 6.35, 2.57-15.7) were an independent risk factor for ischemic stroke. Extracorporeal membrane oxygenation (IRR = 5.32, 1.52-18.6), low-middle income countries (LMIC) vs high income countries (HIC) (IRR = 4.70, 1.62-13.7), and age >55 (IRR = 3.66, 1.23-10.9) were independent risk factors for ICH. Co-morbid neurological conditions (IRR = 3.43, 1.11-10.6), LMIC vs HIC (IRR = 8.69, 2.15-35.2), July-December 2020 vs January-June 2020 (IRR = 0.17, 0.04-0.69) and age >55 (IRR = 4.05, 1.15-14.3) were independent risk factors for seizure.
Conclusions: Decision-making should incorporate salient risk factors to inform management of SARS-CoV2 infection and avoid neurological complications.
... Although the frequencies of epilepsy (4.3%) and seizures (2.2%) were similar to studies from other regions in the world (5.7%-10.0%) [5,12,[18][19][20], the proportion of patients with movement disorders (2.2%) in our study was lower than that of other studies from Europe (9.3%) [20]. ...
Background:
Neurological manifestations of SARS-CoV-2 infection have been reported from many countries around the world, including the South Asian region. This surveillance study aimed to describe the spectrum of neurological disorders associated with COVID-19 in Sri Lanka.
Methods:
COVID-19 patients manifesting neurological disorders one week prior and up to six weeks after infection were recruited from all the neurology centres of the government hospitals in Sri Lanka from May 2021 - May 2022. Data was collected using a structured data form that was electronically transmitted to a central repository. All patients were evaluated and managed by a neurologist. Data were analysed using simple descriptive analysis to characterise demographic and disease related variables, and simple comparisons and logistic regression were performed to analyse outcomes and their associations.
Results:
One hundred and eighty-four patients with neurological manifestations associated with COVID-19 were recruited from all nine provinces in Sri Lanka. Ischaemic stroke (31%) was the commonest neurological manifestation followed by encephalopathy (13.6%), Guillain-Barre syndrome (GBS) (9.2%) and encephalitis (7.6%). Ischaemic stroke, encephalitis and encephalopathy presented within 6 days of onset of COVID-19 symptoms, whereas GBS and myelitis presented up to 10 days post onset while epilepsy and Bell palsy presented up to 20 - 40 days post onset. Haemorrhagic stroke presented either just prior to or at onset, or 10 - 25 days post onset of COVID-19 symptomatic infection. An increased frequency of children presenting with encephalitis and encephalopathy was observed during the Omicron variant predominant period. A poor outcome (no recovery or death) was associated with supplemental oxygen requirement during admission (Odds Ratio: 12.94; p = 0.046).
Conclusions:
The spectrum and frequencies of COVID-19 associated neurological disorders in Sri Lanka were similar to that reported from other countries, with strokes and encephalopathy being the commonest. Requiring supplemental oxygen during hospitalisation was associated with a poor outcome.
Neurological manifestations are frequent in patients with SARS-CoV-2 infection and can be correlated with different pathogenic mechanisms which can be divided into two categories: direct invasion of the central nervous system by the virus and indirect effects deriving from the severity of the systemic infection and by the inflammatory response correlated with cytokine storm. Among the neurological manifestations, acute encephalopathy is very frequent and its nomenclature has recently been updated. The occurrence of a condition of altered mental status, reduced consciousness, delirium up to coma represents an element associated with a greater severity of the infection and mortality both in an Intensive Care Unit setting and in an Emergency Department setting. The tissue damage mechanisms found in COVID-19 patients’ encephalopathy and neuroimaging patterns, as well as histopathology, are similar to those described in sepsis-associated encephalopathy, further confirming the role of indirect mechanisms, with no CNS invasion by the virus. The available data have some limitations, notably the underuse of diagnostic neuroimaging techniques in severely affected patients, particularly in the first wave of the pandemic.
(300/300) Background: In this COVID-19 Critical Care Consortium (CCCC) sub-study, we qualified neurological complications associated with COVID-19 infection, including incidence and outcomes across many countries. Methods: The CCCC is an international, multicenter study. Eligible patients were COVID-19 patients admitted to intensive care units (ICU) in hospitals across 23 centers between January 7th, 2020, to June 23rd, 2022. Incidence of neurological complications was estimated as the number of events per hospital days and per admission using Poisson regression. Associations between neurological complications and clinical risk factors were assessed using multivariable Poisson regression. Results: 713 patients were included, with a median age of 56 years (interquartile range (IQR)=45-65), of which 272 (38.1%) were female. Median ICU days was 14 (IQR=7-25). Neurological complications were reported in 61/480 patients (12.7%) with the most common being ischemic stroke (2.9%), intracranial hemorrhage (ICH) (2.8%), and seizures (2.6%). After adjusting for sex, age, pandemic era, country income status, comorbid neurological conditions, and mechanical ventilation or extracorporeal membrane oxygenation (ECMO), multivariable analysis for neurological complications per admitted days showed comorbid neurological conditions (incidence rate ratio (IRR)=6.35, 2.57-15.7) were an independent risk factor for ischemic stroke. ECMO (IRR=5.32, 1.52-18.6), low-middle income countries (LMIC) vs high income countries (HIC) (IRR=4.70, 1.62-13.7), and age >55 (IRR=3.66, 1.23-10.9) were independent risk factors for ICH. Co-morbid neurological conditions (IRR=3.43, 1.11-10.6), LMIC vs HIC (IRR=8.69, 2.15-35.2), July-December 2020 vs January-June 2020 (IRR=0.17, 0.04-0.69) and age >55 (IRR=4.05, 1.15-14.3) were independent risk factors for seizure. 6.8% of patients with neurological complications had favorable outcomes (modified Rankin Score (mRS) < 3) at discharge compared to 13.2% of patients without complications. Conclusions: Neurological complications were not uncommon in patients with COVID-19 infection. Being from an LMIC was an independent risk factor for neurological complications. Decision-making should incorporate salient risk factors to inform the management of severe COVID-19 infection.
Background
The spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases.
Methods
A systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients.
Results
44 articles were included with a pooled sample size of 13,480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2, 95% CI, 17.2 to 28.1%), taste impairment (19.6, 95% CI, 3.8 to 60.1%), smell impairment (18.3, 95% CI, 15.4 to 76.2%), headache (12.1, 95% CI, 9.1 to 15.8%), dizziness (11.3, 95% CI, 8.5 to 15.0%), and encephalopathy (9.4, 95% CI, 2.8 to 26.6%). Nearly 2.5% (95% CI, 1 to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately.
Conclusions
Neurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.
Background
Patients with dementia are vulnerable during the coronavirus disease 2019 (COVID-19) pandemic, yet few studies describe their hospital course and outcomes.
Objective
To describe and compare the hospital course for COVID-19 patients with dementia to an aging cohort without dementia in a large New York City academic medical center.
Methods
This was a single-center retrospective cohort study describing all consecutive patients age 65 or older with confirmed COVID-19 who presented to the emergency department or were hospitalized at New York-Presbyterian/Columbia University Irving Medical Center between March 6 and April 7, 2020.
Results
A total of 531 patients were evaluated, including 116 (21.8%) with previously diagnosed dementia, and 415 without dementia. Patients with dementia had higher mortality (50.0%versus 35.4%, p = 0.006); despite similar comorbidities and complications, multivariate analysis indicated the association was dependent on age, sex, comorbidities, and code status. Patients with dementia more often presented with delirium (36.2%versus 11.6%, p < 0.001) but less often presented with multiple other COVID-19 symptoms, and these findings remained after adjusting for age and sex.
Conclusion
Hospitalized COVID-19 patients with dementia had higher mortality, but dementia was not an independent risk factor for death. These patients were approximately 3 times more likely to present with delirium but less often manifested or communicated other common COVID-19 symptoms. For this high-risk population in a worsening pandemic, understanding the unique manifestations and course in dementia and aging populations may help guide earlier diagnosis and optimize medical management.
Background: Early reports have detailed a range of neurological symptoms in patients with the SARS-CoV-2 infection. However, there is a lack of detailed description and incidence of the neurological disorders amongst hospitalized COVID-19 patients. We describe a range of neurological disorders (other than non-specific neurological symptoms), including their clinical, radiological, and laboratory findings, encountered in our cohort of COVID-19 patients admitted to a large tertiary institution.
Methods: We reviewed our prospectively collated database of all adult Neurology referrals, Neurology and Stroke admissions and Neurological multi-disciplinary team meetings for all hospitalized patients with suspected or proven COVID-19 from 17 March 2020 to 31 August 2020.
Results: Twenty-nine of 1,243 COVID-19 inpatients (2.3%) presented with COVID-19-related neurological disorders. The mean age was 68.9 ± 13.5(SD) years, age range of 34–97 years, and there were 16 males. Twenty two patients had confirmed, five were probable and two had suspected COVID-19 infection according to the WHO case classification. Eight patients (27%) required critical care admission. Neurological symptoms at presentation included acute confusion and delirium, seizures, and new focal neurological deficits. Based on the pre-defined neurological phenotype, COVID-19 patients were grouped into four main categories. Sixteen patients had cerebrovascular events (13 with acute ischemic stroke and three had hemorrhagic features), seven patients were found to have inflammatory, non-inflammatory and autoimmune encephalopathy (including two with known Multiple Sclerosis), whilst disorders of movement and peripheral nervous system were diagnosed in three patients each.
Conclusion: Although the exact prevalence and etiology remain unclear, new onset of neurological disorders, in addition to anosmia, is non-sporadic during the acute COVID-19-infection. Longitudinal follow-up of these patients is required to determine the clinical and functional outcome, treatment response and long-term effects of the SARS-CoV-2 infection.
Coronavirus disease 2019 (COVID-19) is emerging as the greatest public health crisis in the early 21st century. Its causative agent, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is an enveloped single- stranded positive-sense ribonucleic acid virus that enters cells via the angiotensin converting enzyme 2 receptor or several other receptors. While COVID-19 primarily affects the respiratory system, other organs including the brain can be involved. In Western clinical studies, relatively mild neurological dysfunction such as anosmia and dysgeusia is frequent (~70-84%) while severe neurologic disorders such as stroke (~1-6%) and meningoenceph- alitis are less common. It is unclear how much SARS-CoV-2 infection contributes to the incidence of stroke given co-morbidities in the affected patient population. Rarely, clinically-defined cases of acute disseminated enceph- alomyelitis, Guillain-Barré syndrome and acute necrotizing encephalopathy have been reported in COVID-19 pa- tients. Common neuropathological findings in the 184 patients reviewed include microglial activation (42.9%) with microglial nodules in a subset (33.3%), lymphoid inflammation (37.5%), acute hypoxic-ischemic changes (29.9%), astrogliosis (27.7%), acute/subacute brain infarcts (21.2%), spontaneous hemorrhage (15.8%), and mi-
crothrombi (15.2%). In our institutional cases, we also note occasional anterior pituitary infarcts. COVID-19 co- agulopathy, sepsis, and acute respiratory distress likely contribute to a number of these findings. When present, central nervous system lymphoid inflammation is often minimal to mild, is detected best by immunohistochemistry and, in one study, indistinguishable from control sepsis cases. Some cases evince microglial nodules or neu- ronophagy, strongly supporting viral meningoencephalitis, with a proclivity for involvement of the medulla ob- longata. The virus is detectable by reverse transcriptase polymerase chain reaction, immunohistochemistry, or electron microscopy in human cerebrum, cerebellum, cranial nerves, olfactory bulb, as well as in the olfactory epithelium; neurons and endothelium can also be infected. Review of the extant cases has limitations including selection bias and limited clinical information in some cases. Much remains to be learned about the effects of direct viral infection of brain cells and whether SARS-CoV-2 persists long-term contributing to chronic symptomatology.
Objective: The SARS-Cov2 virus is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its impact on disease outcome are poorly characterized. The objective of the study is to determine if neurological syndromes are associated with increased risk of inpatient mortality.
Methods: 581 hospitalized patients with confirmed SARS-Cov2 infection, neurological involvement and brain-imaging were compared to hospitalized non-neurological COVID-19 patients. Four patterns of neurological manifestations were identified –acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, pre-existing comorbidities, vital-signs, laboratory values, and pattern of neurological manifestations. Significant predictors were incorporated into a disease-severity score. Patients with neurological manifestations were matched with patients of the same age and disease severity to assess the risk of death.
Results: 4711 patients with confirmed SARS-Cov2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurological issues of sufficient concern to warrant neuro-imaging. These patients were compared to 1743 non-neurological COVID-19 patients matched for age and disease-severity admitted during the same period. Patients with altered mentation (n=258, p =0.04, OR 1.39, CI 1.04 – 1.86) or radiologically confirmed stroke (n=55, p = 0.001, OR 3.1, CI 1.65-5.92) had a higher risk of mortality than age and severity-matched controls.
Conclusions: The incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19.
New York City (NYC) was an epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the United States during spring 2020 (1). During March-May 2020, approximately 203,000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). To obtain more complete data, DOHMH used supplementary information sources and relied on direct data importation and matching of patient identifiers for data on hospitalization status, the occurrence of death, race/ethnicity, and presence of underlying medical conditions. The highest rates of cases, hospitalizations, and deaths were concentrated in communities of color, high-poverty areas, and among persons aged ≥75 years or with underlying conditions. The crude fatality rate was 9.2% overall and 32.1% among hospitalized patients. Using these data to prevent additional infections among NYC residents during subsequent waves of the pandemic, particularly among those at highest risk for hospitalization and death, is critical. Mitigating COVID-19 transmission among vulnerable groups at high risk for hospitalization and death is an urgent priority. Similar to NYC, other jurisdictions might find the use of supplementary information sources valuable in their efforts to prevent COVID-19 infections.
In a cohort of 106,543 patients discharged after an index COVID-19 hospitalization, 9% experienced at least one readmission to the same hospital within 2 months of discharge. More than one readmission occurred in 1.6% of cases. In this analysis, the odds of hospital readmission increased with age among persons aged ≥65 years, presence of one of five selected chronic conditions, hospitalization within the 3 months preceding the index hospitalization, and if discharge from the index hospitalization was to a SNF or to home with health care assistance. Although the proportions of patients in the Premier Healthcare Database cohort who were non-Hispanic Black (23%) or Hispanic (21%) were higher than those proportions in the U.S. Census (13% and 18%, respectively), their odds of readmission were lower than those of non-Hispanic White patients. The slight association of readmission with lengths of stay for hospitalized COVID-19 patients merits further study. These results are comparable to those of recently published analyses, which found a similar group of chronic conditions to be significantly associated with hospital readmission (6,7) and could be explained by the complications of underlying conditions in the presence of COVID-19 (8), COVID-19 sequelae (3), or indirect effects of the COVID-19 pandemic (9). Although only a small proportion of patients discharged to home or self-care were readmitted, 7% returned to the hospital within a median of 7 days. One explanation for their readmission is that approximately two thirds of these 4,406 patients had one or more of the selected chronic conditions. © 2020 Department of Health and Human Services. All rights reserved.
Importance: Delirium is common among older emergency department (ED) patients, is associated with high morbidity and mortality, and frequently goes unrecognized. Anecdotal evidence has described atypical presentations of coronavirus disease 2019 (COVID-19) in older adults; however, the frequency of and outcomes associated with delirium in older ED patients with COVID-19 infection have not been well described.
Objective: To determine how frequently older adults with COVID-19 present to the ED with delirium and their associated hospital outcomes.
Design, setting, and participants: This multicenter cohort study was conducted at 7 sites in the US. Participants included consecutive older adults with COVID-19 presenting to the ED on or after March 13, 2020.
Exposure: COVID-19 was diagnosed by positive nasal swab for severe acute respiratory syndrome coronavirus 2 (99% of cases) or classic radiological findings (1% of cases).
Main outcomes and measures: The primary outcome was delirium as identified from the medical record according to a validated record review approach.
Results: A total of 817 older patients with COVID-19 were included, of whom 386 (47%) were male, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean (SD) age of patients was 77.7 (8.2) years. Of included patients, 226 (28%) had delirium at presentation, and delirium was the sixth most common of all presenting symptoms and signs. Among the patients with delirium, 37 (16%) had delirium as a primary symptom and 84 (37%) had no typical COVID-19 symptoms or signs, such as fever or shortness of breath. Factors associated with delirium were age older than 75 years (adjusted relative risk [aRR], 1.51; 95% CI, 1.17-1.95), living in a nursing home or assisted living (aRR, 1.23; 95% CI, 0.98-1.55), prior use of psychoactive medication (aRR, 1.42; 95% CI, 1.11-1.81), vision impairment (aRR, 1.98; 95% CI, 1.54-2.54), hearing impairment (aRR, 1.10; 95% CI 0.78-1.55), stroke (aRR, 1.47; 95% CI, 1.15-1.88), and Parkinson disease (aRR, 1.88; 95% CI, 1.30-2.58). Delirium was associated with intensive care unit stay (aRR, 1.67; 95% CI, 1.30-2.15) and death (aRR, 1.24; 95% CI, 1.00-1.55).
Conclusions and relevance: In this cohort study of 817 older adults with COVID-19 presenting to US emergency departments, delirium was common and often was seen without other typical symptoms or signs. In addition, delirium was associated with poor hospital outcomes and death. These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation.
Objective:
Covid-19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid-19.
Methods:
We examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid-19 within a hospital network in Chicago, Illinois. We compared the severity of Covid-19 and outcomes in patients with and without neurologic manifestations. We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression.
Results:
Neurologic manifestations were present at Covid-19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid-19 (OR 4.02; 95% CI 2.04-8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968-0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0-2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001).
Interpretation:
Neurologic manifestations occur in most hospitalized Covid-19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.
Introduction: Multiple risk factors of mortality have been identified in patients with
COVID-19. Here, we sought to determine the effect of a history of neurological disorder
and development of neurological manifestations on mortality in hospitalized patients
with COVID-19.
Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory
confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio.
Previous history of neurological disease was classified by severity (major or minor).
Neurological manifestations during disease course were also grouped into major and
minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures
were defined as major manifestations, whereas minor neurological manifestations
included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate
logistic regression models were used to determine significant predictors of mortality in
patients with COVID-19 infection.
Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the
574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women.
Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND),
of which 204 (35.5%) had a major history of neurological disease (HND). Mortality
rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002),
although this was not a significant predictor of death. Major neurological manifestations
were recorded in 203/574 (35.4%) patients during disease course. The mortality
rate in patients who had major neurological manifestations was 37.4% compared
to 11.9% (p = 2 × 10−12) in those who did not. In multivariate analysis, major
neurological manifestation (OR 2.1, CI 1.3-3.4; p = 0.002) was a predictor of death.
Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19.
Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection.
Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10⁻¹²) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1, CI 1.3-3.4; p = 0.002) was a predictor of death.
Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.
There is increasing evidence that patients with Coronavirus disease 19 (COVID-19) present with neurological and psychiatric symptoms. Anosmia, hypogeusia, headache, nausea and altered consciousness are commonly described, although there are emerging clinical reports of more serious and specific conditions such as acute cerebrovascular accident, encephalitis and demyelinating disease. Whether these presentations are directly due to viral invasion of the central nervous system (CNS) or caused by indirect mechanisms has yet to be established. Neuropathological examination of brain tissue at autopsy will be essential to establish the neuro-invasive potential of the SARS-CoV-2 virus but, to date, there have been few detailed studies. The pathological changes in the brain probably represent a combination of direct cytopathic effects mediated by SARS-CoV-2 replication or indirect effects due to respiratory failure, injurious cytokine reaction, reduced immune response and cerebrovascular accidents induced by viral infection. Further large-scale molecular and cellular investigations are warranted to clarify the neuropathological correlates of the neurological and psychiatric features seen clinically in COVID-19. In this review, we summarise the current reports of neuropathological examination in COVID-19 patients, in addition to our own experience, and discuss their contribution to the understanding of CNS involvement in this disease.
Background and objectives:
One year since the onset of the COVID-19 pandemic, we aimed to summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality.
Methods:
We searched PubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31st December 2019 to 15th December 2020 for studies enrolling consecutive COVID-19 patients presenting with neurological manifestations. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.
Results:
Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence- 2%). In COVID-19 patients aged ≥60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91).
Discussion:
Up to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.
Background
Little is known regarding long-term outcomes of patients hospitalized with COVID-19.
Methods
We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep.
Results
Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23–3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29–0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups.
Conclusions
Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.
Background
Toxic metabolic encephalopathy (TME) has been reported in 7–31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients.Methods
We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase–polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission.ResultsAmong 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02–1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21–2.00, P = 0.001).ConclusionsTME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.
This study describes reasons for readmission, use of ICU interventions during readmission, and proportions of death after initial hospital discharge of COVID-19 patients from US Veterans Affairs (VA) hospitals in March-June 2020.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) for which there have been over 50 million confirmed cases and 1.2 million deaths globally. While many SARS-CoV-2 infected individuals are asymptomatic or experience respiratory symptoms, extrapulmonary manifestations, including neurological symptoms and conditions, are increasingly recognized. There remains no clear understanding of the mechanisms that underlie neurological symptoms in COVID-19 and whether SARS-CoV-2 has the potential for neuroinvasion in humans. In this minireview, we discuss what is known from human autopsies in fatal COVID-19, including highlighting studies that investigate for the presence of SARS-CoV-2 in brain and olfactory tissue, and summarize the neuropathological consequences of infection. Incorporating microscopic and molecular findings from brain tissue into what we know about clinical disease will inform best practice management guidance and direct research priorities as it relates to neurological morbidity from COVID-19.
Objective:
To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes.
Methods:
We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders.
Results:
Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001).
Conclusions:
Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.
Background:
Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS.
Methods:
In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions.
Findings:
43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70-86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes.
Interpretation:
In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included.
Funding:
German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).
Background and Purpose
Information on stroke survivors infected with coronavirus disease 2019 (COVID-19) is limited. The aim of this study was to describe specific clinical characteristics and outcomes of patients with COVID-19 with a history of stroke.
Methods
All the confirmed cases of COVID-19 at Tongji Hospital from January 27 to March 5, 2020, were included in our cohort study. Clinical data were analyzed and compared between patients with and without a history of stroke.
Results
Of the included 1875 patients with COVID-19, 50 patients had a history of stroke. The COVID-19 patients with medical history of stroke were older with more comorbidities, had higher neutrophil count, and lower lymphocyte and platelet counts than those without history of stroke. The levels of D-dimers, cardiac troponin I, NT pro-brain natriuretic peptide, and interleukin-6 were also markedly higher in patients with history of stroke. Stroke survivors who underwent COVID-19 developed more acute respiratory distress syndrome and received more noninvasive mechanical ventilation. Data from propensity-matched analysis indicated a higher proportion of patients with COVD-19 with a history of stroke were admitted to the intensive care unit requiring mechanical ventilation and were more likely to be held in the unit or die, compared with non-stroke history COVID-19 patients.
Conclusions
Patients with COVID-19 with a history of stroke had more severe clinical symptoms and poorer outcomes compared with those without a history of stroke.
Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed.
The Vaccine Adverse Event Reporting System (VAERS), administered by the FDA and CDC, is the U.S. system for surveillance of vaccine adverse events (AE). Acute encephalopathy age <18 months (EO < 18), age > or =18 months (EO > or = 18), encephalitis (EI), and multiple sclerosis (MS) after vaccination have been reported to VAERS, but reports often contain insufficient information to validate diagnoses. Standardized case definitions would enhance the utility of VAERS reports for AE surveillance. We developed practical case definitions for classification of VAERS reports, and three neurologists independently applied the definitions to reports submitted in 1993. Inter-observer agreement was assessed, and non-concordant classifications were reviewed in a follow-up conference call. Reports of EO < 18 (n = 8), EO > or = 18 (n = 20), EI (n = 15), and MS (n = 16) were classified as "definite" in 7% to 30% of the cases, while 26% to 51% of reports were thought to have insufficient information to make a classification. Agreement among reviewers was good to excellent, (kappa: 0.65 to 0.85) except for EO < 18 m for which it was marginal (kappa: 0.37). It is possible to develop reproducible case definitions for acute encephalopathy, encephalitis, and multiple sclerosis using a standardized approach. Application of standardized case definitions to VAERS reports documents the limited information in many reports, specifies data for supplemental collection, and indicates that VAERS reports should be cautiously interpreted. Development and application of case definitions for other adverse events reported after vaccination should enhance the value of vaccine safety databases. Published by Elsevier Science Inc.
Invited Review: the spectrum of neuropathology in COVID-19
- Al-Sarraj
COVID-19 outbreak-New York city
- Cnbj Thompson
- J Baumgartner
- C Pichardo
Thompson CNBJ, Baumgartner J, Pichardo C, et al. COVID-19 outbreak-New
York city, February 29-June 1, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(46):
1725-1729.
SARS-CoV-2 detected in cerebrospinal fluid by PCR in a case of COVID-19 encephalitis
- Y H Huang
- D Jiang
- J T Huang
Huang YH, Jiang D, Huang JT. SARS-CoV-2 detected in cerebrospinal fluid by PCR
in a case of COVID-19 encephalitis. Brain Behav Immun. 2020;87:149.
Invited Review: the spectrum of neuropathology in COVID-19
- S Al-Sarraj
- C Troakes
- B Hanley
Al-Sarraj S, Troakes C, Hanley B, et al. Invited Review: the spectrum of neuropathology in COVID-19. Neuropathol Appl Neurobiol. 2021;47(1):3-16.
Readmission and death after initial hospital discharge among patients with COVID-19 in a large multihospital system
- Jpwx Donnelly
- T J Iwashyna
- H C Prescott
- Donnelly JPWX
Neuropathology of COVID-19 (neuro-COVID): clinicopathological update
- J J Lou
- M Movassaghi
- D Gordy
- Lou JJ