COVID-19 severity is related to poor executive function in people with post-COVID conditions.
COVID-19
Executive function
Neuropsychological test
Post-acute COVID-19 syndrome
Symptom assessment
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
14
11
2022
accepted:
23
01
2023
revised:
20
01
2023
medline:
27
4
2023
pubmed:
21
3
2023
entrez:
20
3
2023
Statut:
ppublish
Résumé
Patients with post-coronavirus disease 2019 (COVID-19) conditions typically experience cognitive problems. Some studies have linked COVID-19 severity with long-term cognitive damage, while others did not observe such associations. This discrepancy can be attributed to methodological and sample variations. We aimed to clarify the relationship between COVID-19 severity and long-term cognitive outcomes and determine whether the initial symptomatology can predict long-term cognitive problems. Cognitive evaluations were performed on 109 healthy controls and 319 post-COVID individuals categorized into three groups according to the WHO clinical progression scale: severe-critical (n = 77), moderate-hospitalized (n = 73), and outpatients (n = 169). Principal component analysis was used to identify factors associated with symptoms in the acute-phase and cognitive domains. Analyses of variance and regression linear models were used to study intergroup differences and the relationship between initial symptomatology and long-term cognitive problems. The severe-critical group performed significantly worse than the control group in general cognition (Montreal Cognitive Assessment), executive function (Digit symbol, Trail Making Test B, phonetic fluency), and social cognition (Reading the Mind in the Eyes test). Five components of symptoms emerged from the principal component analysis: the "Neurologic/Pain/Dermatologic" "Digestive/Headache", "Respiratory/Fever/Fatigue/Psychiatric" and "Smell/ Taste" components were predictors of Montreal Cognitive Assessment scores; the "Neurologic/Pain/Dermatologic" component predicted attention and working memory; the "Neurologic/Pain/Dermatologic" and "Respiratory/Fever/Fatigue/Psychiatric" components predicted verbal memory, and the "Respiratory/Fever/Fatigue/Psychiatric," "Neurologic/Pain/Dermatologic," and "Digestive/Headache" components predicted executive function. Patients with severe COVID-19 exhibited persistent deficits in executive function. Several initial symptoms were predictors of long-term sequelae, indicating the role of systemic inflammation and neuroinflammation in the acute-phase symptoms of COVID-19." Study Registration: www.ClinicalTrials.gov , identifier NCT05307549 and NCT05307575.
Identifiants
pubmed: 36939932
doi: 10.1007/s00415-023-11587-4
pii: 10.1007/s00415-023-11587-4
pmc: PMC10026205
doi:
Banques de données
ClinicalTrials.gov
['NCT05307575', 'NCT05307549']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2392-2408Subventions
Organisme : Agència de Gestió d'Ajuts Universitaris i de Recerca
ID : 202PANDE00053
Organisme : Fundació la Marató de TV3
ID : 202111-30-31-32
Investigateurs
Jose A Bernia
(JA)
Vanesa Arauzo
(V)
Marta Balague-Marmaña
(M)
Berta Valles-Pauls
(B)
Jesús Caballero
(J)
Anna Carnes-Vendrell
(A)
Gerard Piñol-Ripoll
(G)
Ester Gonzalez-Aguado
(E)
Carme Tayó-Juli
(C)
Eva Forcadell-Ferreres
(E)
Silvia Reverte-Vilarroya
(S)
Susanna Forné
(S)
Jordina Muñoz-Padros
(J)
Anna Bartes-Plan
(A)
Jose A Muñoz-Moreno
(JA)
Anna Prats-Paris
(A)
Inmaculada Rico
(I)
Nuria Sabé
(N)
Laura Casas
(L)
Marta Almeria
(M)
Maria José Ciudad
(MJ)
Anna Ferré
(A)
Manuela Lozano
(M)
Tamar Garzon
(T)
Marta Cullell
(M)
Sonia Vega
(S)
Sílvia Alsina
(S)
Maria J Maldonado-Belmonte
(MJ)
Susana Vazquez-Rivera
(S)
Sandra Navarro
(S)
Eva Baillès
(E)
Informations de copyright
© 2023. The Author(s).
Références
Soriano JB, Murthy S, Marshall JC et al (2022) A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 22:e102–e107. https://doi.org/10.1016/S1473-3099(21)00703-9/ATTACHMENT/EF4FD06B-88FA-4A0C-B837-DCFEE13E82D7/MMC1.PDF
doi: 10.1016/S1473-3099(21)00703-9/ATTACHMENT/EF4FD06B-88FA-4A0C-B837-DCFEE13E82D7/MMC1.PDF
pubmed: 34951953
Davis HE, Assaf GS, McCorkell L, et al (2021) Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine 38:101019. https://doi.org/10.1016/J.ECLINM.2021.101019/ATTACHMENT/499C606A-AE36-49F5-87DD-09E3B87369C9/MMC1.DOCX
Guo P, Benito Ballesteros A, Yeung SP, et al (2022) COVCOG 1: factors predicting physical, neurological and cognitive symptoms in long COVID in a community sample. a first publication from the COVID and cognition study. Front Aging Neurosci 14:. https://doi.org/10.3389/FNAGI.2022.804922/FULL
Ziauddeen N, Gurdasani D, O’Hara ME, et al (2022) Characteristics and impact of Long Covid: Findings from an online survey. PLoS One 17:e0264331. https://doi.org/10.1371/JOURNAL.PONE.0264331
García‐Sánchez C, Calabria M, Grunden N, et al (2022) Neuropsychological deficits in patients with cognitive complaints after COVID‐19. Brain Behav e2508. https://doi.org/10.1002/brb3.2508
Delgado-Alonso C, Valles-Salgado M, Delgado-Álvarez A et al (2022) Cognitive dysfunction associated with COVID-19: A comprehensive neuropsychological study. J Psychiatr Res 150:40–46. https://doi.org/10.1016/j.jpsychires.2022.03.033
doi: 10.1016/j.jpsychires.2022.03.033
pubmed: 35349797
pmcid: 8943429
Ariza M, Cano N, Segura B, et al (2022) Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints. Front Aging Neurosci 1–12. https://doi.org/10.3389/fnagi.2022.1029842
Almeria M, Cejudo JC, Sotoca J, et al (2020) Cognitive profile following COVID-19 infection: Clinical predictors leading to neuropsychological impairment. Brain Behav Immun Health 9:100163. https://doi.org/10.1016/J.BBIH.2020.100163
Hampshire A, Chat A, Mphil M, et al (2022) Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort. EClinical Medicine 47:1–10. https://doi.org/10.1016/j.eclinm.2022.101417
Hampshire A, Trender W, Chamberlain SR, et al (2021) Cognitive deficits in people who have recovered from COVID-19. EClinicalMedicine 39:101044. https://doi.org/10.1016/j.eclinm.2021.101044
Cecchetti G, Agosta F, Canu E et al (2022) Cognitive, EEG, and MRI features of COVID-19 survivors: a 10-month study. J Neurol 269:3400–3412. https://doi.org/10.1007/s00415-022-11047-5
doi: 10.1007/s00415-022-11047-5
pubmed: 35249144
pmcid: 8898558
Ferrucci R, Dini M, Rosci C et al (2022) One-year cognitive follow-up of COVID-19 hospitalized patients. Eur J Neurol 29:2006. https://doi.org/10.1111/ENE.15324
doi: 10.1111/ENE.15324
pubmed: 35285122
pmcid: 9111730
Becker JH, Lin JJ, Doernberg M et al (2021) Assessment of cognitive function in patients after COVID-19 infection. JAMA Netw Open 4:e2130645–e2130645. https://doi.org/10.1001/JAMANETWORKOPEN.2021.30645
doi: 10.1001/JAMANETWORKOPEN.2021.30645
pubmed: 34677597
pmcid: 8536953
Vannorsdall TD, Brigham E, Fawzy A et al (2022) Cognitive dysfunction, psychiatric distress, and functional decline after COVID-19. J Acad Consult Liaison Psychiatry 63:133–143. https://doi.org/10.1016/J.JACLP.2021.10.006
doi: 10.1016/J.JACLP.2021.10.006
pubmed: 34793996
Santoyo-Mora M, Villaseñor-Mora C, Cardona-Torres LM et al (2022) COVID-19 Long-term effects: is there an impact on the simple reaction time and alternative-forced choice on recovered patients? Brain Sci 12:1258. https://doi.org/10.3390/BRAINSCI12091258
doi: 10.3390/BRAINSCI12091258
pubmed: 36138994
pmcid: 9496861
Ollila H, Pihlaja R, Koskinen S et al (2022) Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study. Crit Care 26:1–11. https://doi.org/10.1186/s13054-022-04092-z
doi: 10.1186/s13054-022-04092-z
Woo MS, Malsy J, Pöttgen J et al (2020) Frequent neurocognitive deficits after recovery from mild COVID-19. Brain Commun. https://doi.org/10.1093/braincomms/fcaa205
doi: 10.1093/braincomms/fcaa205
pubmed: 33376990
pmcid: 7717144
Wild CJ, Norton L, Menon DK et al (2022) Disentangling the cognitive, physical, and mental health sequelae of COVID-19. Cell Rep Med. https://doi.org/10.1016/J.XCRM.2022.100750
doi: 10.1016/J.XCRM.2022.100750
pubmed: 36103880
pmcid: 9448696
Miskowiak KW, Johnsen S, Sattler SM et al (2021) Cognitive impairments four months after COVID-19 hospital discharge: Pattern, severity and association with illness variables. Eur Neuropsychopharmacol 46:39. https://doi.org/10.1016/J.EURONEURO.2021.03.019
doi: 10.1016/J.EURONEURO.2021.03.019
pubmed: 33823427
pmcid: 8006192
Premraj L, Kannapadi N v., Briggs J, et al (2022) Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: a meta-analysis. J Neurol Sci 434:120162. https://doi.org/10.1016/J.JNS.2022.120162
Singhavi H, Pai A, Mair M et al (2021) SARS-Cov2: a meta-analysis of symptom distribution by continent in 7310 adult COVID-19 infected patients. Virusdisease 32:400–409. https://doi.org/10.1007/S13337-021-00699-Y/FIGURES/5
doi: 10.1007/S13337-021-00699-Y/FIGURES/5
pubmed: 34124318
pmcid: 8187893
Lechien JR, Chiesa-Estomba CM, de Siati DR, et al (2020) Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. European Archives of Oto-Rhino-Laryngology
Mao L, Jin H, Wang M, et al (2020) Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2020.1127
Proal AD, VanElzakker MB (2021) Long COVID or post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms. Front Microbiol 12:. https://doi.org/10.3389/FMICB.2021.698169
Zhou Z, Kang H, Li S, Zhao X (2020) Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms. J Neurol 1. https://doi.org/10.1007/s00415-020-09929-7
Guo P, Benito Ballesteros A, Yeung SP, et al (2022) COVCOG 2: cognitive and memory deficits in long COVID: a second publication from the COVID and Cognition Study. Front Aging Neurosci 14:. https://doi.org/10.3389/FNAGI.2022.804937/FULL
Nasreddine ZS, Phillips NA, Bédirian V et al (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699. https://doi.org/10.1111/j.1532-5415.2005.53221.x
doi: 10.1111/j.1532-5415.2005.53221.x
pubmed: 15817019
Ojeda N, del Pino R, Ibarretxe-Bilbao N, et al (2016) [Montreal Cognitive Assessment Test: normalization and standardization for Spanish population]. Rev Neurol 63:488–496. https://doi.org/10.33588/rn.6311.2016241
Wechsler D (2001) Wais III. Escala de inteligencia de wechsler para adultos. Manual de aplicación. TEA Ediciones. Departamento I+D., Barcelona
Schmidt M (1996) Rey Auditory and Verbal Learning Test: A handbook. LosAngeles, CA
Alviarez-Schulze V, Cattaneo G, Pachón-García C, et al (2022) Validation and normative data of the spanish version of the rey auditory verbal learning test and associated long-term forgetting measures in middle-aged adults. Front Aging Neurosci 14:. https://doi.org/10.3389/fnagi.2022.809019
Reitan RMM (1958) Validity of the trail making test as an indicator of organic brain damage. Perceptual and Motos Skills 8:271–276. https://doi.org/10.2466/PMS.8.7.271-276
doi: 10.2466/PMS.8.7.271-276
Lezak, M. D., Howieson, D. B., Bigler, E. D., & Tranel D (2012) Neuropsychological assessment, 5th ed
Benton AL, Hamsher K (1989) Multilingual Aphasia Examination. AJA Associates, Iowa
Peña-Casanova J, Quiñones-Úbeda S, Gramunt-Fombuena N et al (2009) Spanish multicenter normative studies (NEURONORMA Project): norms for verbal fluency tests. Arch Clin Neuropsychol 24:395–411. https://doi.org/10.1093/ARCLIN/ACP042
doi: 10.1093/ARCLIN/ACP042
pubmed: 19648583
Ardila A, Ostrosky-Solís F, Bernal B (2006) Cognitive testing toward the future: the example of semantic verbal fluency (ANIMALS). Int J Psychol 41:324–332. https://doi.org/10.1080/00207590500345542
doi: 10.1080/00207590500345542
Golden CJ (2005) Test de colores y palabras (Stroop). Madrid
Allegri RF, Mangone CA, Villavicencio AF et al (1997) Spanish boston naming test norms. Clin Neuropsychol 11:416–420. https://doi.org/10.1080/13854049708400471
doi: 10.1080/13854049708400471
Fernández-Abascal EG, Cabello R, Fernández-Berrocal P, Baron-Cohen S (2013) Test-retest reliability of the “Reading the Mind in the Eyes” test: A one-year follow-up study. Mol Autism 4:1–6. https://doi.org/10.1186/2040-2392-4-33/TABLES/2
doi: 10.1186/2040-2392-4-33/TABLES/2
Gomar JJ, Ortiz-Gil J, McKenna PJ et al (2011) Validation of the Word Accentuation Test (TAP) as a means of estimating premorbid IQ in Spanish speakers. Schizophr Res 128:175–176. https://doi.org/10.1016/j.schres.2010.11.016
doi: 10.1016/j.schres.2010.11.016
pubmed: 21144711
Jackson C (2015) The Chalder Fatigue Scale (CFQ 11). Occup Med (Chic Ill) 65:86–86. https://doi.org/10.1093/OCCMED/KQU168
doi: 10.1093/OCCMED/KQU168
García-Campayo J, Zamorano E, Ruiz MA et al (2010) Cultural adaptation into Spanish of the generalized anxiety disorder-7 (GAD-7) scale as a screening tool. Health Qual Life Outcomes 8:8. https://doi.org/10.1186/1477-7525-8-8
doi: 10.1186/1477-7525-8-8
pubmed: 20089179
pmcid: 2831043
Spitzer RL, Kroenke K, Williams JBW, Löwe B (2006) A Brief Measure for Assessing Generalized Anxiety Disorder: The GAD-7. Arch Intern Med 166:1092–1097. https://doi.org/10.1001/ARCHINTE.166.10.1092
doi: 10.1001/ARCHINTE.166.10.1092
pubmed: 16717171
Kroenke K, Spitzer RL, Williams JBW (2001) The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 16:606. https://doi.org/10.1046/J.1525-1497.2001.016009606.X
doi: 10.1046/J.1525-1497.2001.016009606.X
pubmed: 11556941
pmcid: 1495268
Diez-Quevedo C, Rangil T, Sanchez-Planell L et al (2001) Validation and utility of the patient health questionnaire in diagnosing mental disorders in 1003 general hospital spanish inpatients. Psychosom Med 63:679–686
doi: 10.1097/00006842-200107000-00021
pubmed: 11485122
WHOQOL-BREF (1996) WHOQOL-BREF : introduction, administration, scoring and generic version of the assessment : field trial version, December. World Health Organization 1–16
Marshall JC, Murthy S, Diaz J et al (2020) A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 20:e192–e197. https://doi.org/10.1016/S1473-3099(20)30483-7
doi: 10.1016/S1473-3099(20)30483-7
Hopkins RO, Weaver LK, Pope D, et al (1999) Neuropsychological Sequelae and Impaired Health Status in Survivors of Severe Acute Respiratory Distress Syndrome
Serrano R, Corbella X, Rello J (2021) Management of hypoxemia in SARS-CoV-2 infection: lessons learned from one year of experience, with a special focus on silent hypoxemia. J Intensive Med 1:26–30. https://doi.org/10.1016/J.JOINTM.2021.02.001
doi: 10.1016/J.JOINTM.2021.02.001
pubmed: 36943810
pmcid: 7939974
Dhont S, Derom E, van Braeckel E et al (2020) The pathophysiology of “happy” hypoxemia in COVID-19. Respir Res 21:1–9. https://doi.org/10.1186/s12931-020-01462-5
doi: 10.1186/s12931-020-01462-5
Brugulat-Serrat A, Salvadó G, Operto G et al (2020) White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants. Hum Brain Mapp 41:1309. https://doi.org/10.1002/HBM.24877
doi: 10.1002/HBM.24877
pubmed: 31778002
Penke L, Mañiega SM, Bastin ME, et al (2012) Brain-wide white matter tract integrity is associated with information processing speed and general intelligence. Molecular Psychiatry 2012 17:10 17:955–955. https://doi.org/10.1038/MP.2012.127
Patel SK, Hanly PJ, Smith EE et al (2015) Nocturnal hypoxemia is associated with white matter hyperintensities in patients with a minor stroke or transient ischemic attack. J Clin Sleep Med 11:1417. https://doi.org/10.5664/JCSM.5278
doi: 10.5664/JCSM.5278
pubmed: 26194729
pmcid: 4661334
Radnis C, Qiu S, Jhaveri M, et al (2020) Radiographic and clinical neurologic manifestations of COVID-19 related hypoxemia. J Neurol Sci 418:117119. https://doi.org/10.1016/J.JNS.2020.117119
Huang S, Zhou Z, Yang D et al (2022) Persistent white matter changes in recovered COVID-19 patients at the 1-year follow-up. Brain 145:1830–1838. https://doi.org/10.1093/BRAIN/AWAB435
doi: 10.1093/BRAIN/AWAB435
pubmed: 34918020
Paniz-Mondolfi A, Bryce C, Grimes Z et al (2020) Central nervous system involvement by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2). J Med Virol. https://doi.org/10.1002/jmv.25915
doi: 10.1002/jmv.25915
pubmed: 32761908
pmcid: 7361761
Sankowski R, Mader S, Valdés-Ferrer SI (2015) Systemic Inflammation and the Brain: Novel Roles of Genetic, Molecular, and Environmental Cues as Drivers of Neurodegeneration. Front Cell Neurosci 9:. https://doi.org/10.3389/FNCEL.2015.00028
Liddelow SA, Guttenplan KA, Clarke LE, et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017 541:7638 541:481–487. https://doi.org/10.1038/NATURE21029
Wang Z, Yang Y, Liang X, et al (2020) COVID-19 Associated Ischemic Stroke and Hemorrhagic Stroke: Incidence, Potential Pathological Mechanism, and Management. Front Neurol 11:571996. https://doi.org/10.3389/FNEUR.2020.571996
Whiteside DM, Basso MR, Naini SM et al (2022) Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection Part 1: Cognitive functioning. Clinical Neuropsychologist 36:806–828. https://doi.org/10.1080/13854046.2022.2030412
doi: 10.1080/13854046.2022.2030412
pubmed: 35130818
Ferrucci R, Dini M, Groppo E et al (2021) Long-lasting cognitive abnormalities after COVID-19. Brain Sci 11:1–11. https://doi.org/10.3390/brainsci11020235
doi: 10.3390/brainsci11020235
Mattioli F, Stampatori C, Righetti F et al (2021) Neurological and cognitive sequelae of Covid-19: a four month follow-up. J Neurol 268:4422. https://doi.org/10.1007/S00415-021-10579-6
doi: 10.1007/S00415-021-10579-6
pubmed: 33932157
pmcid: 8088203
Henneghan AM, Lewis KA, Gill E, Kesler SR (2022) Cognitive Impairment in Non-critical, Mild-to-Moderate COVID-19 Survivors. Front Psychol 13:770459. https://doi.org/10.3389/fpsyg.2022.770459
Lorent N, Weygaerde Y vande, Claeys E, et al (2022) Prospective longitudinal evaluation of hospitalised COVID-19 survivors 3 and 12 months after discharge. ERJ Open Res 8:. https://doi.org/10.1183/23120541.00004-2022
Stavem K, Einvik G, Tholin B, et al (2022) Cognitive function in non-hospitalized patients 8–13 months after acute COVID-19 infection: a cohort study in Norway. PLoS One 17:e0273352. https://doi.org/10.1371/JOURNAL.PONE.0273352
Crunfli F, Carregari VC, Veras FP, et al (2022) Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. Proc Natl Acad Sci U S A 119:. https://doi.org/10.1073/pnas.2200960119
Douaud G, Lee S, Alfaro-Almagro F, et al (2022) SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 2022 604:7907 604:697–707. https://doi.org/10.1038/s41586-022-04569-5
Boldrini M, Canoll PD, Klein RS (2021) How COVID-19 Affects the Brain. JAMA Psychiat 78:682–683. https://doi.org/10.1001/JAMAPSYCHIATRY.2021.0500
doi: 10.1001/JAMAPSYCHIATRY.2021.0500
Colbenson GA, Johnson A, Wilson ME (2019) Post-intensive care syndrome: impact, prevention, and management. Breathe 15:98–101. https://doi.org/10.1183/20734735.0013-2019
doi: 10.1183/20734735.0013-2019
pubmed: 31191717
pmcid: 6544795
Walker KA, Ficek BN, Westbrook R (2019) Understanding the role of systemic inflammation in Alzheimer’s disease. ACS Chem Neurosci 10:3340–3342. https://doi.org/10.1021/ACSCHEMNEURO.9B00333/ASSET/IMAGES/LARGE/CN-2019-00333X_0001.JPEG
doi: 10.1021/ACSCHEMNEURO.9B00333/ASSET/IMAGES/LARGE/CN-2019-00333X_0001.JPEG
pubmed: 31241312
Butowt R, von Bartheld CS (2022) The route of SARS-CoV-2 to brain infection: have we been barking up the wrong tree? Mol Neurodegener 17:1–4. https://doi.org/10.1186/S13024-022-00529-9/FIGURES/1
doi: 10.1186/S13024-022-00529-9/FIGURES/1
Reppucci CJ, Petrovich GD (2015) Organization of connections between the amygdala, medial prefrontal cortex, and lateral hypothalamus: a single and double retrograde tracing study in rats. Brain Structure and Function 2015 221:6 221:2937–2962. https://doi.org/10.1007/S00429-015-1081-0
Chiappetta S, Sharma AM, Bottino V, Stier C (2020) COVID-19 and the role of chronic inflammation in patients with obesity. Int J Obes 44:1790–1792. https://doi.org/10.1038/s41366-020-0597-4
doi: 10.1038/s41366-020-0597-4
Chu Y, Yang J, Shi J, et al (2020) Obesity is associated with increased severity of disease in COVID-19 pneumonia: a systematic review and meta-analysis. Eur J Med Res 25:. https://doi.org/10.1186/S40001-020-00464-9
Selim BJ, Ramar K, Surani S (2016) Obe Intensive Care Unit 44:146–156. https://doi.org/10.1080/21548331.2016.1179558
doi: 10.1080/21548331.2016.1179558