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      Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19

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          Abstract

          COVID-19, the infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. It dramatically affects people's health and daily life. Neurological complications are increasingly documented for patients with COVID-19. However, the effect of COVID-19 on the brain is less studied, and existing quantitative neuroimaging analyses of COVID-19 were mainly based on the univariate voxel-based morphometry analysis (VBM) that requires corrections for a large number of tests for statistical significance, multivariate approaches that can reduce the number of tests to be corrected have not been applied to study COVID-19 effect on the brain yet. In this study, we leveraged source-based morphometry (SBM) analysis, a multivariate extension of VBM, to identify changes derived from computed tomography scans in covarying gray matter volume patterns underlying COVID-19 in 120 neurological patients (including 58 cases with COVID-19 and 62 patients without COVID-19 matched for age, gender and diseases). SBM identified that lower gray matter volume (GMV) in superior/medial/middle frontal gyri was significantly associated with a higher level of disability (modified Rankin Scale) at both discharge and six months follow-up phases even when controlling for cerebrovascular diseases. GMV in superior/medial/middle frontal gyri was also significantly reduced in patients receiving oxygen therapy compared to patients not receiving oxygen therapy. Patients with fever presented significant GMV reduction in inferior/middle temporal gyri and fusiform gyrus compared to patients without fever. Patients with agitation showed GMV reduction in superior/medial/middle frontal gyri compared to patients without agitation. Patients with COVID-19 showed no significant GMV differences from patients without COVID-19 in any brain region. Results suggest that COVID-19 may affect the frontal-temporal network in a secondary manner through fever or lack of oxygen.

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          Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

          Dawei Wang, Bo Hu, Fangfang Zhu … (2020)
          In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
          Article 0 comments Cited 10915 times – based on 0 reviews     Review now
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            Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

            Ling Mao, Huijuan Jin, Mengdie Wang … (2020)
            The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.
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              Neurologic Features in Severe SARS-CoV-2 Infection

              Julie Helms, Stéphane Kremer, Hamid Merdji … (2020)
              To the Editor: We report the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19. The patients received similar evaluations by intensivists in two intensive care units (ICUs) in Strasbourg, France, between March 3 and April 3, 2020. Six patients were excluded because of paralytic neuromuscular blockade when neurologic data were collected or because they had died without a neurologic examination having been performed. In all 58 patients, reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of nasopharyngeal samples were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median age of the patients was 63 years, and the median Simplified Acute Physiology Score II at the time of neurologic examination was 52 (interquartile range, 37 to 65, on a scale ranging from 0 to 163, with higher scores indicating greater severity of illness). Seven patients had had previous neurologic disorders, including transient ischemic attack, partial epilepsy, and mild cognitive impairment. The neurologic findings were recorded in 8 of the 58 patients (14%) on admission to the ICU (before treatment) and in 39 patients (67%) when sedation and a neuromuscular blocker were withheld. Agitation was present in 40 patients (69%) when neuromuscular blockade was discontinued (Table 1). A total of 26 of 40 patients were noted to have confusion according to the Confusion Assessment Method for the ICU; those patients could be evaluated when they were responsive (i.e., they had a score of −1 to 1 on the Richmond Agitation and Sedation Scale, on a scale of −5 [unresponsive] to +4 [combative]). Diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes were present in 39 patients (67%). Of the patients who had been discharged at the time of this writing, 15 of 45 (33%) had had a dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command. Magnetic resonance imaging (MRI) of the brain was performed in 13 patients (Figs. S1 through S3 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Although these patients did not have focal signs that suggested stroke, they underwent MRI because of unexplained encephalopathic features. Enhancement in leptomeningeal spaces was noted in 8 patients, and bilateral frontotemporal hypoperfusion was noted in all 11 patients who underwent perfusion imaging. Two asymptomatic patients each had a small acute ischemic stroke with focal hyperintensity on diffusion-weighted imaging and an overlapping decreased apparent diffusion coefficient, and 1 patient had a subacute ischemic stroke with superimposed increased diffusion-weighted imaging and apparent diffusion coefficient signals. In the 8 patients who underwent electroencephalography, only nonspecific changes were detected; 1 of the 8 patients had diffuse bifrontal slowing consistent with encephalopathy. Examination of cerebrospinal fluid (CSF) samples obtained from 7 patients showed no cells; in 2 patients, oligoclonal bands were present with an identical electrophoretic pattern in serum, and protein and IgG levels were elevated in 1 patient. RT-PCR assays of the CSF samples were negative for SARS-CoV-2 in all 7 patients. In this consecutive series of patients, ARDS due to SARS-CoV-2 infection was associated with encephalopathy, prominent agitation and confusion, and corticospinal tract signs. Two of 13 patients who underwent brain MRI had single acute ischemic strokes. Data are lacking to determine which of these features were due to critical illness–related encephalopathy, cytokines, or the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Neurobiol Stress
                Journal ID (iso-abbrev): Neurobiol Stress
                Title: Neurobiology of Stress
                Publisher: The Author(s). Published by Elsevier Inc.
                ISSN (Electronic): 2352-2895
                Publication date PMC-release: 13 April 2021
                Publication date (Electronic): 13 April 2021
                Electronic Location Identifier: 100326
                Affiliations
                [a ]Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, USA
                [b ]Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), GA, Georgia Tech, Emory, Atlanta, USA
                [c ]Stroke Unit, Azienda Socio Sanitaria Territoriale Spedali Civili, Spedali Civili Hospital, Brescia, Italy
                [d ]Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Italy
                [e ]Department of Computer Science, Georgia State University, Atlanta, USA
                [f ]Neuroradiology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy
                [g ]Department of Psychology, Computer Science, Neurosciences, Mathematics & Statistics, Georgia State University, Atlanta, USA
                Author notes
                [∗ ]Corresponding author. TReNDS Center, 55 Park Place NE, 18th floor, Atlanta, GA, 30303, USA.
                Article
                Publisher Item ID: S2352-2895(21)00034-5 Publisher ID: 100326
                DOI: 10.1016/j.ynstr.2021.100326
                PMC ID: 8041745
                PubMed ID: 33869679
                SO-VID: 7be1b916-c706-463e-b298-78caad7b83c6
                Copyright © © 2021 The Author(s). Published by Elsevier Inc.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 4 February 2021
                Date revision received : 3 April 2021
                Date accepted : 5 April 2021
                Categories
                Subject: Article

                Keywords: covid-19,computed tomography,gray matter volume,frontal-temporal network,source-based morphometry
                Data availability:
                Keywords: covid-19, computed tomography, gray matter volume, frontal-temporal network, source-based morphometry

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