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1.
JAMA Netw Open ; 4(5): e2112131, 2021 05 03.
Article in English | MEDLINE | ID: covidwho-1222587

ABSTRACT

Importance: The COVID-19 pandemic continues to affect millions of people globally, with increasing reports of neurological manifestations but limited data on their incidence and associations with outcome. Objective: To determine the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19. Design, Setting, and Participants: This cohort study included patients with clinically diagnosed or laboratory-confirmed COVID-19 at 28 centers, representing 13 countries and 4 continents. The study was performed by the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) from March 1 to September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) from March to October 2020. Three cohorts were included: (1) the GCS-NeuroCOVID all COVID-19 cohort (n = 3055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; (2) the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and (3) the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation. Exposures: Clinically diagnosed or laboratory-confirmed COVID-19. Main Outcomes and Measures: Neurological phenotypes were classified as self-reported symptoms or neurological signs and/or syndromes assessed by clinical evaluation. Composite incidence was reported for groups with at least 1 neurological manifestation. The main outcome measure was in-hospital mortality. Results: Of the 3055 patients in the all COVID-19 cohort, 1742 (57%) were men, and the mean age was 59.9 years (95% CI, 59.3-60.6 years). Of the 475 patients in the COVID-19 neurological cohort, 262 (55%) were men, and the mean age was 62.6 years (95% CI, 61.1-64.1 years). Of the 214 patients in the ENERGY cohort, 133 (62%) were men, and the mean age was 67 years (95% CI, 52-78 years). A total of 3083 of 3743 patients (82%) across cohorts had any neurological manifestation (self-reported neurological symptoms and/or clinically captured neurological sign and/or syndrome). The most common self-reported symptoms included headache (1385 of 3732 patients [37%]) and anosmia or ageusia (977 of 3700 patients [26%]). The most prevalent neurological signs and/or syndromes were acute encephalopathy (1845 of 3740 patients [49%]), coma (649 of 3737 patients [17%]), and stroke (222 of 3737 patients [6%]), while meningitis and/or encephalitis were rare (19 of 3741 patients [0.5%]). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death (adjusted odds ratio [aOR], 5.99; 95% CI, 4.33-8.28) after adjusting for study site, age, sex, race, and ethnicity. Presence of preexisting neurological disorders (aOR, 2.23; 95% CI, 1.80-2.75) was associated with increased risk of developing neurological signs and/or syndromes with COVID-19. Conclusions and Relevance: In this multicohort study, neurological manifestations were prevalent among patients hospitalized with COVID-19 and were associated with higher in-hospital mortality. Preexisting neurological disorders were associated with increased risk of developing neurological signs and/or syndromes in COVID-19.


Subject(s)
COVID-19/mortality , Global Health/statistics & numerical data , Hospitalization/statistics & numerical data , Nervous System Diseases/mortality , SARS-CoV-2 , Adult , Aged , COVID-19/complications , Female , Hospital Mortality , Humans , Incidence , Male , Middle Aged , Nervous System Diseases/virology , Odds Ratio , Prevalence
2.
JAMA Neurol ; 78(5): 536-547, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1118065

ABSTRACT

Importance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures: Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 µg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.


Subject(s)
COVID-19/complications , Nervous System Diseases/etiology , Systemic Inflammatory Response Syndrome/etiology , Adolescent , COVID-19/etiology , COVID-19/mortality , Child , Child, Preschool , Critical Care , Female , Hospitalization , Humans , Male , Nervous System Diseases/mortality , Patient Discharge/statistics & numerical data , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Systemic Inflammatory Response Syndrome/complications , Treatment Outcome , United States/epidemiology
3.
Neurology ; 95(7): e910-e920, 2020 08 18.
Article in English | MEDLINE | ID: covidwho-1115264

ABSTRACT

OBJECTIVE: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19). METHODS: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period. RESULTS: One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0-83.8 years vs 70.1 years, IQR 52.9-78.6 years, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7-1.1 vs 0.5, IQR 0.4-0.6, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, p = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0, p < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, p < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21-16.5, p = 0.025), lower platelet count (OR 0.98, 95% CI 0.97-0.99, p = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00-1.03, p = 0.009) on admission. CONCLUSIONS: Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.


Subject(s)
Coronavirus Infections/epidemiology , Inpatients/statistics & numerical data , Nervous System Diseases/epidemiology , Pneumonia, Viral/epidemiology , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , COVID-19 , Case-Control Studies , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Hospital Mortality , Humans , Italy/epidemiology , Male , Middle Aged , Nervous System Diseases/diagnosis , Nervous System Diseases/mortality , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
4.
Neurology ; 96(4): e575-e586, 2021 01 26.
Article in English | MEDLINE | ID: covidwho-1048797

ABSTRACT

OBJECTIVE: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes. METHODS: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City 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 patients with COVID-19 with and without neurologic disorders. RESULTS: Of 4,491 patients with COVID-19 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 reverse transcriptase 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, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [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 patients with COVID-19 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.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Hospitalization/statistics & numerical data , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Adult , Age Factors , Aged , Brain Diseases/epidemiology , Brain Diseases/etiology , COVID-19/mortality , Female , Hospital Mortality , Humans , Intubation, Intratracheal/statistics & numerical data , Male , Middle Aged , Nervous System Diseases/mortality , Neurotoxicity Syndromes , New York City/epidemiology , Organ Dysfunction Scores , Patient Discharge/statistics & numerical data , Prospective Studies , Sex Factors , Spinal Cord Diseases/epidemiology , Spinal Cord Diseases/etiology , Young Adult
6.
Curr Neurovasc Res ; 17(4): 522-530, 2020.
Article in English | MEDLINE | ID: covidwho-688646

ABSTRACT

Coronavirus is an enveloped, non-segmented, positive-polarity and single-stranded RNA virus. It has four types of genera that infect mammals and birds, with only alpha and beta types found to affect humans with varying severity. A specific clade of beta coronaviruses is reported as lethal zoonotic viruses and has created major epidemic troubles, starting with the severe acute respiratory syndrome (SARS) in 2002, then the Middle East respiratory syndrome (MERS) in 2012, and lastly Coronavirus Disease 2019 (COVID-19) in 2019. However, many neurological complications reported in COVID-19 patients have highlighted a critical pattern of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Awareness of such an association could create new insight to consider neurological manifestations as a COVID-19 differential diagnosis during the pandemic period of COVID-19 to avoid delayed diagnosis and prevent further transmission. This mini-review aims to collect the current knowledge regarding the mechanism behind the neuroinvasive capacity of SARS-CoV-2, to summarize the common documented neurological symptoms and associated complications in COVID-19 patients, and to review the impact of neurological manifestations on COVID-19 mortality.


Subject(s)
COVID-19 , Coronavirus Infections , Nervous System Diseases/mortality , SARS-CoV-2/pathogenicity , Animals , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Humans , Nervous System Diseases/etiology , Nervous System Diseases/virology
8.
Neurol Sci ; 41(9): 2317-2324, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-635550

ABSTRACT

INTRODUCTION: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. METHODS: In this retrospective cohort study, we included 103 adult inpatients (aged ≥ 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. RESULTS: In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer's dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. CONCLUSIONS: Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Nervous System Diseases/diagnosis , Nervous System Diseases/mortality , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Age Factors , Aged , Aged, 80 and over , COVID-19 , Cohort Studies , Female , Humans , Lung Diseases/diagnosis , Lung Diseases/mortality , Male , Middle Aged , Mortality/trends , Pandemics , Predictive Value of Tests , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2
9.
J Neurovirol ; 26(3): 311-323, 2020 06.
Article in English | MEDLINE | ID: covidwho-599674

ABSTRACT

Coronavirus disease 2019 (COVID-19), first reported in Wuhan, the capital of Hubei, China, has been associated to a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In March 2020, the World Health Organization declared the SARS-CoV-2 infection a global pandemic. Soon after, the number of cases soared dramatically, spreading across China and worldwide. Italy has had 12,462 confirmed cases according to the Italian National Institute of Health (ISS) as of March 11, and after the "lockdown" of the entire territory, by May 4, 209,254 cases of COVID-19 and 26,892 associated deaths have been reported. We performed a review to describe, in particular, the origin and the diffusion of COVID-19 in Italy, underlying how the geographical circulation has been heterogeneous and the importance of pathophysiology in the involvement of cardiovascular and neurological clinical manifestations.


Subject(s)
Cardiovascular Diseases/epidemiology , Coronavirus Infections/epidemiology , Cytokine Release Syndrome/epidemiology , Nervous System Diseases/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Age Factors , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Cardiovascular Diseases/virology , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/transmission , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Geography , Humans , Italy/epidemiology , Nervous System Diseases/diagnosis , Nervous System Diseases/mortality , Nervous System Diseases/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/transmission , Prevalence , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/transmission , Sex Factors , Survival Analysis
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