neurology – ETIDIoH

#Surveillance #Study of Acute #Neurological Manifestations among 439 #Egyptian Patients with #COVID19 in Assiut and Aswan University #Hospitals (Neuroepidemiol., abstract)

[Source: Neuroepidemiology, full page: (LINK). Abstract, edited.]

Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals

Khedr E.M.a · Abo-Elfetoh N.a · Deaf E.b · Hassan H.M.b · Amin M.T.c · Soliman R.K.d · Attia A.A.e · Zarzour A.A.e · Zain M.f · Mohamed-Hussein A.g · Hashem M.K.g · Hassany S.M.h · Aly A.i · Shoyb A.j · Saber M.j

Author affiliations: a Department of Neuropsychiatry, Assiut University Hospital, Faculty of Medicine, Assiut, Egypt; b Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; c Department of Public Health and Community Medicine, Assiut University Hospital, Faculty of Medicine, Assiut, Egypt; d Department of Radiology, Assiut University Hospital, Faculty of Medicine, Assiut, Egypt; e Department of Anesthesia and Intensive Care, Faculty of Medicine, Assiut University, Assiut, Egypt; f Department of Internal Medicine, Assiut University Hospital, Faculty of Medicine, Assiut, Egypt; g Department of Chest, Assiut University Hospital, Faculty of Medicine, Assiut, Egypt; h Department of Tropical Medicine and GIT, Assiut University Hospital, Faculty of Medicine, Assiut, Egypt; i Department of Neurosurgery, Assiut University Hospital, Faculty of Medicine, Aswan, Egypt; j Department of Neuropsychiatry, Assiut University Hospital, Faculty of Medicine, Aswan, Egypt

Neuroepidemiology | DOI: https://doi.org/10.1159/000513647

Abstract

Background:

COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals.

Materials and Methods:

We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated.

Results:

439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection.

Conclusion:

In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.

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Keywords: SARS-CoV-2; COVID-19; Neurology; Egypt.

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Post-infectious #myasthenia gravis in a #COVID19 patient (Kompass Ophthalmol., abstract)

[Source: Kompass Ophthalmologie, full page: (LINK). Abstract, edited.]

Post-infectious myasthenia gravis in a COVID-19 patient

Huber M. A · Rogozinski S. A · doll W. b · Framme C. c · Höglinger G. A · Hufendiek K. c · Wegner F. a

Author affiliations: a Department of Neurology, Hannover Medical School, Hannover, Germany; b Institute of Virology, Hannover Medical School, Hannover, Germany; c Department of Ophthalmology, Hannover Medical School, Hannover, Germany

Kompass ophthalmol | DOI: https://doi.org/10.1159/000514490

Summary

Objective:

In the present work we report on the case of a young woman with post-infectious occurrence of myasthenia gravis after a COVID-19 infection with mild respiratory symptoms and anosmia / ageusia one month before admission to our neurological department.

Methods:

The patient data came from the medical records of the Hannover Medical School. The patient’s written consent was available.

Results:

The 21-year-old patient presented with subacute, vertically displaced double vision as a result of right-sided partial oculomotor nerve paresis and ptosis. Mild respiratory symptoms, headache and body aches without fever, and anosmia / ageusia had occurred about four weeks earlier. During the last-mentioned symptoms, which lasted for about ten days, the patient had already noticed “tired eyes” and fluctuating double vision. The clinical examination, including a positive test with edrophonium chloride and the detection of elevated acetylcholine receptor antibodies, indicated an etiological connection with the ocular manifestation of myasthenia gravis. With three different serological tests (Abbott, DiaSorin, Euroimmun), antibodies (IgA / IgG) against SARS-CoV-2 were detected in the serum, which speaks for this specific coronavirus as the pathogen of the previous infection in this patient. The myasthenic syndrome was successfully treated with intravenous immunoglobulins and oral pyridostigmine.

Conclusion:

This is the first case report of post-infectious myasthenia gravis as a neurological complication in a COVID-19 patient.

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Keywords: SARS-CoV-2; COVID-19; Myastenia gravis; Neurology; Ophthalmology.

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Inflammatory #cytokine #patterns associated with #neurological #diseases in #COVID19 (Ann Neurol., abstract)

[Source: Annals of Neurology, full page: (LINK). Abstract, edited.]

Inflammatory cytokine patterns associated with neurological diseases in COVID‐19

Otávio M Espíndola PhD, Yago C P Gomes MSc., Carlos Otávio Brandão MD, PhD, Rafael C Torres PhD, Marilda Siqueira PhD, Cristiane N Soares PhD, Marco Antonio S D Lima PhD, Ana Claudia C B Leite PhD, Carolina O Venturotti MD, Ana Julia C Carvalho MD, Guilherme Torezani MD, Abelardo Q C Araujo MD, PhD, Marcus Tulius T Silva MD, PhD

First published: 06 February 2021 | DOI: https://doi.org/10.1002/ana.26041

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ana.26041.

Abstract

Patients with COVID‐19 can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of IL‐2, IL‐4, IL‐6, IL‐10, IL‐12, CXCL8, and CXCL10 in the cerebrospinal fluid (CSF). Conversely, encephalopathy was associated with high serum levels of IL‐6, CXCL8, and active TGF‐β1. Inflammatory syndromes of the central nervous system (CNS) in COVID‐19 can appear early, as a para‐infectious process without significant systemic involvement, or without direct evidence of SARS‐CoV‐2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines.

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Keywords: SARS-CoV-2; COVID-19; Hyperinflammation; Immunopathology; Encephalopathy; Neurology.

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The Association between Presence of #Comorbidities and #COVID19 #Severity: A Systematic Review and Meta-Analysis (Cerebrovasc Dis., abstract)

[Source: Cerebrovascular Diseases, full page: (LINK). Abstract, edited.]

The Association between Presence of Comorbidities and COVID-19 Severity: A Systematic Review and Meta-Analysis

Honardoost M.a,b · Janani L.c · Aghili R.a · Emami Z.a · Khamseh M.E.a

Author affiliations: a Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran; b Cardio-Oncology Research Center, Rajaie Cardiovascular Medical & Research Center, Iran University of Medical Sciences, Tehran, Iran; c Biostatistics Department, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

Cerebrovasc Dis | DOI: https://doi.org/10.1159/000513288

Abstract

Aim:

Several studies reported the accompaniment of severe COVID-19 with comorbidities. However, there is not a systematic evaluation of all aspects of this association. Therefore, this meta-analysis aimed to assess the association between all underlying comorbidities in COVID-19 infection severity.

Methods:

Electronic literature search was performed via scientific search engines. After the removal of duplicates and selection of articles of interest, 28 studies were included. A fixed-effects model was used; however, if heterogeneity was high (I2 > 50%) a random-effects model was applied to combine the data.

Results:

A total of 6,270 individuals were assessed (1,615 severe and 4,655 non-severe patients). The median age was 63 (95% confidence interval [CI]: 49–74) and 47 (95% CI: 19–63) years in the severe and non-severe groups, respectively. Moreover, about 41% of patients had comorbidities. Severity was higher in patients with a history of cerebrovascular disease: OR 4.85 (95% CI: 3.11–7.57). The odds of being in a severe group increase by 4.81 (95% CI: 3.43–6.74) for a history of cardiovascular disease (CVD). This was 4.19 (95% CI: 2.84–6.19) for chronic lung disease and 3.18, 95% CI: 2.09–4.82 for cancer. The odds ratios of diabetes and hypertension were 2.61 (95% CI: 2.02–3.3) and 2.37 (95% CI: 1.80–3.13), respectively.

Conclusions:

The presence of comorbidities is associated with severity of COVID-19 infection. The strongest association was observed for cerebrovascular disease, followed by CVD, chronic lung disease, cancer, diabetes, and hypertension.

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Keywords: SARS-CoV-2; COVID-19; Neurology.

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#Neuroinflammation and #Brain #Development: Possible #Risk Factors in #COVID19-Infected #Children (Neuroimmunomod., abstract)

[Source: Neuroimmunomodulation, full page: (LINK). Abstract, edited.]

Neuroinflammation and Brain Development: Possible Risk Factors in COVID-19-Infected Children

da Silva Chagas L.a · Sandre P.C.b · de Velasco P.C.c · Marcondes H.a · Ribeiro e Ribeiro N.C.A.a · Barreto A.L.a · Alves Mauro L.B.a · Ferreira J.H.a · Serfaty C.A.a,d

Author affiliations: a Laboratory of Neural Plasticity, Neurobiology Department, Biology Institute, Federal Fluminense University, Niteroi, Brazil; b Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; c Department of Applied Nutrition, Institute of Nutrition, Rio de Janeiro State University, Rio de Janeiro, Brazil; d National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

Neuroimmunomodulation | DOI: https://doi.org/10.1159/000512815

Abstract

COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus, affects children in a different way than it does in adults, with milder symptoms. However, several cases of neurological symptoms with neuroinflammatory syndromes, such as the multisystem inflammatory syndrome (MIS-C), following mild cases, have been reported. As with other viral infections, such as rubella, influenza, and cytomegalovirus, SARS-CoV-2 induces a surge of proinflammatory cytokines that affect microglial function, which can be harmful to brain development. Along with the viral induction of neuroinflammation, other noninfectious conditions may interact to produce additional inflammation, such as the nutritional imbalance of fatty acids and polyunsaturated fatty acids and alcohol consumption during pregnancy. Additionally, transient thyrotoxicosis induced by SARS-CoV-2 with secondary autoimmune hypothyroidism has been reported, which could go undetected during pregnancy. Together, those factors may pose additional risk factors for SARS-CoV-2 infection impacting mechanisms of neural development such as synaptic pruning and neural circuitry formation. The present review discusses those conditions in the perspective of the understanding of risk factors that should be considered and the possible emergence of neurodevelopmental disorders in COVID-19-infected children.

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Keywords: SARS-CoV-2; COVID-19; Pediatrics; Neurology.

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#Pediatric Ischemic #Stroke: An Infrequent #Complication of #SARS‐CoV‐2 (Ann Neurol., abstract)

[Source: Annals of Neurology, full page: (LINK). Abstract, edited.]

Pediatric Ischemic Stroke: An Infrequent Complication of SARS‐CoV‐2

Lauren A. Beslow MD, MSCE, Alexandra B. Linds MSc, Christine K. Fox MD, MAS, Manoëlle Kossorotoff MD, PhD, Yenny C. Zuñiga Zambrano MD, Marta Hernández‐Chávez MD, Sahar M. A. Hassanein MD, PhD, Susan Byrne MD, PhD, Ming Lim MD, PhD, Nkechi Maduaka MbChB, BSc, Dimitrios Zafeiriou MD, PhD, Michael M. Dowling MD, PhD, MSCS, Ryan J. Felling MD, PhD, Mubeen F. Rafay MBBS, MSc, Laura L. Lehman MD, Michael J. Noetzel MD, Timothy J. Bernard MD, MSCS, Nomazulu Dlamini MBBS, MSc, PhD, International Pediatric Stroke Study Group

First published: 17 December 2020 | DOI:
https://doi.org/10.1002/ana.25991

Abstract

Objective

Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS‐CoV‐2 is unknown. This study aimed to determine the proportion of pediatric SARS‐CoV‐2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS‐CoV‐2 in the first 3 months of the pandemic in an international cohort.

Methods

We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS‐CoV‐2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS‐CoV‐2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS‐CoV‐2 from March 1 to May 31, 2020.

Results

Of 42 centers with SARS‐CoV‐2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS‐CoV‐2 had ischemic strokes. Proportions of stroke cases positive for SARS‐CoV‐2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS‐CoV‐2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS‐CoV‐2. Seven of 8 patients with SARS‐CoV‐2 and stroke had additional established stroke risk factors.

Interpretation

As in adults, pediatric stroke is an infrequent complication of SARS‐CoV‐2, and SARS‐CoV‐2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS‐CoV‐2 in pediatric stroke better, SARS‐CoV‐2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021

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Keywords: SARS-CoV-2; COVID-19; Pediatrics; Stroke; Neurology.

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Absent Blood Oxygen Level–Dependent #fMRI Activation of the #Orbitofrontal #Cortex in a Patient With Persistent #Cacosmia and #Cacogeusia After #COVID19 Infection (JAMA Neurol., summary)

[Source: JAMA Neurology, full page: (LINK). Summary, edited.]

Absent Blood Oxygen Level–Dependent Functional Magnetic Resonance Imaging Activation of the Orbitofrontal Cortex in a Patient With Persistent Cacosmia and Cacogeusia After COVID-19 Infection

Ismail Ibrahim Ismail, MSc1; Khaled A. Gad, MD2,3

Author Affiliations: 1 Department of Neurology, Ibn Sina Hospital, Sabah Health Region, Kuwait; 2 Department of Radiology, Ibn Sina Hospital, Sabah Health Region, Kuwait; 3 Diagnostic Radiology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

JAMA Neurol. Published online January 22, 2021. doi:10.1001/jamaneurol.2021.0009

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A25-year-old woman with no relevant medical history developed fever, generalized body pain, dry cough, anosmia, and ageusia in April 2020. She was diagnosed with coronavirus disease 2019 (COVID-19) by positive findings on polymerase chain reaction assay and positive findings on computed tomography of the chest. Her clinical course was uncomplicated, and she was treated conservatively. Anosmia and ageusia started to improve during the following month. However, during the recovery phase, she started to experience offensive odor (cacosmia) and taste (cacogeusia) with stimulation of these sensations. Ear, nose, and throat evaluation showed normal clinical and endoscopic nasal examination findings. Computed tomography findings of the paranasal sinuses were unremarkable. She was given oral and intranasal corticosteroids, in addition to multivitamins, zinc, and olfactory training. However, her symptoms persisted for 3 months, and she was referred to our neurology clinic for further evaluation. Findings of her neurological examination were normal.

(…)

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Keywords: SARS-CoV-2; COVID-19; Ageusia; Anosmia; Neurology.

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Disease modifying #therapies and #Covid19 #severity in #MS (Ann Neurol., abstract)

[Source: Annals of Neurology, full page: (LINK). Abstract, edited.]

Disease modifying therapies and Covid‐19 severity in Multiple Sclerosis

Maria Pia Sormani Ph.D., Nicola De Rossi M.D., Irene Schiavetti Ph.D., Luca Carmisciano M.D., Cinzia Cordioli M.D., Lucia Moiola M.D., Marta Radaelli M.D.. Paolo Immovilli M.D., Marco Capobianco M.D., Maria Trojano M.D., Paola Zaratin Ph.D. Gioacchino Tedeschi M.D., Giancarlo Comi M.D., Mario Alberto Battaglia M.D., Francesco Patti M.D., Marco Salvetti M.D., Musc‐19 study group

First published: 21 January 2021 | DOI: https://doi.org/10.1002/ana.26028

Abstract

Objective

To assess the impact of immunosuppressive and immunomodulatory therapies on the severity of Coronavirus disease 2019 (Covid‐19) in people with MS (PwMS).

Methods

We retrospectively collected data of PwMS with suspected or confirmed Covid‐19. All the patients had complete follow up to death or recovery. Severe Covid‐19 was defined by a 3‐level variable: mild disease not requiring hospitalization vs pneumonia or hospitalization vs Intensive Care Unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated to a severe Covid‐19 by multivariable and Propensity‐Score (PS)‐weighted ordinal logistic models. Sensitivity analyses were run to confirm the results.

Results

Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) Covid‐19, 13 (1.54%) died: 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty‐eight (4.5%) were admitted to an ICU; 99 (11.7%) had a radiologically documented pneumonia; 96 (11.4%) were hospitalized.

After adjusting for region, age, sex, progressive MS course, EDSS, disease duration, BMI, comorbidities and recent methylprednisolone use, the therapy with an anti‐CD20 agent (Ocrelizumab or Rituximab) was significantly associated (OR = 2.37,95%CI = 1.18–4.74,p = 0.015) with an increased risk of severe Covid‐19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24,95%CI = 2.20–12.53, p = 0.001). Results were confirmed by the PS‐weighted and by all the sensitivity analyses.

Interpretation

This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the Covid‐19 pandemic is persisting.

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Keywords: SARS-CoV-2; COVID-19; Multiple Sclerosis; Neurology.

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#Inflammatory #leptomeningeal #cytokines mediate #COVID19 #neurologic symptoms in #cancer patients (Cancer Cell, abstract)

[Source: Cancer Cell, full page: (LINK). Abstract, edited.]

Inflammatory leptomeningeal cytokines mediate COVID-19 neurologic symptoms in cancer patients

Jan Remsik, Jessica A. Wilcox, N. Esther Babady, Tracy A. McMillen, Behroze, A. Vachha, Neil A. Halpern, Vikram Dhawan, Marc Rosenblum, Christine A. Iacobuzio- Donahue, Edward K. Avila, Bianca Santomasso, Adrienne Boire

Published: January 16, 2021 | DOI: https://doi.org/10.1016/j.ccell.2021.01.007

Highlights

Inflammatory cytokines are detected in the CSF weeks after SARS-CoV-2 infection
Levels of IFN-β and IL-8 are specifically enriched in the CSF compared to plasma
CSF markers of senescence and neurodegeneration are consistent with neuronal injury
Intracranial levels of MMP-10 correlate with the degree of neurologic disability

Summary

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks following the acute respiratory infection. To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID- 19, including a targeted proteomics analysis of the cerebrospinal fluid. We find that cancer patients with neurologic sequela of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuro-invasion. The majority of these inflammatory mediators are driven by type 2 interferon and are known to induce neuronal injury in other disease states. In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks following convalescence from acute respiratory infection. These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction. Our findings suggest a role for anti-inflammatory treatment(s) in the management of neurologic complications of COVID-19 infection.

Keywords: SARS-CoV-2 – COVID-19 – neuroinflammation – encephalopathy – cancer – cerebrospinal fluid

Publication History Accepted: January 12, 2021 – Received in revised form: December 18, 2020 – Received: October 7, 2020

Publication stage In Press Accepted Manuscript

Identification DOI: https://doi.org/10.1016/j.ccell.2021.01.007

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Keywords: SARS-CoV-2; COVID-19; Cytokines; Neurology.

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#Prevalence and #risk #factors for #delirium in critically ill patients with #COVID19 (COVID-D): a multicentre cohort study (Lancet Resp Med., abstract)

[Source: Lancet Respiratory Medicine, full page: (LINK). Abstract, edited.]

Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study

Brenda T Pun, DNP, Prof Rafael Badenes, MD , Gabriel Heras La Calle, MD, Onur M Orun, MS, Wencong Chen, PhD, Rameela Raman, PhD, Beata-Gabriela K Simpson, MPH, Stephanie Wilson-Linville, BSN, Borja Hinojal Olmedillo, MD, Ana Vallejo de la Cueva, PhD, Prof Mathieu van der Jagt, MD, Rosalía Navarro Casado, MD, Pilar Leal Sanz, MD, Günseli Orhun, MD, Carolina Ferrer Gómez, MD, Karla Núñez Vázquez, MD, Patricia Piñeiro Otero, MD, Prof Fabio Silvio Taccone, MD, Elena Gallego Curto, MD, Anselmo Caricato, MD, Hilde Woien, PhD, Guillaume Lacave, MD, Hollis R O’Neal Jr, MD, Sarah J Peterson, PhD, Nathan E Brummel, MD, Timothy D Girard, MD, Prof E Wesley Ely, MD, Prof Pratik P Pandharipande, MD for the COVID-19 Intensive Care International Study Group

Published: January 08, 2021 | DOI: https://doi.org/10.1016/S2213-2600(20)30552-X

Summary

Background

To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae.

Methods

This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression.

Findings

Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation–Sedation Scale score while on invasive mechanical ventilation was –4 (–5 to –3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU.

Interpretation

Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19.

Funding

None.

Translations

For the French and Spanish translations of the abstract see Supplementary Materials section.

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Keywords: SARS-CoV-2; COVID-19; Delirium; Neurology; Intensive Care.

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