Neurological manifestations and clinical outcomes in hospitalized patients with COVID-19: Retrospective cohort in a Peruvian hospital
DOI:
https://doi.org/10.35434/rcmhnaaa.2023.164.1979Keywords:
COVID-19, Nervous system, Mortality, Polyneuropathies, respiration, ArtificialAbstract
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.
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Leven Y, Bösel J. Neurological manifestations of COVID-19 - an approach to categories of pathology. Neurol Res Pract. 2021;3(1):39. doi: 10.1186/s42466-021-00138-9.
Forero K, Buqaileh R, Sunderman C, AbouAlaiwi W. COVID-19 and Neurological Manifestations. Brain Sci. 2023;13(8):1137. doi: 10.3390/brainsci13081137.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020;395(10229):1033–1034. doi: 10.1016/S0140-6736(20)30628-0.
Guerrero JI, Barragán LA, Martínez JD et al. Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. BMC Infect Dis. 2021;21(1):515. doi: 10.1186/s12879-021-06185-6.
Thakur KT, Chu VT, Hughes C, Kim CI, Fleck-Derderian S, Barrett C, et al. Risk Factors for New Neurologic Diagnoses in Hospitalized Patients With COVID-19: A Case-Control Study in New York City. Neurol Clin Pract. 2022;12(4):e66–e74. doi: 10.1212/CPJ.0000000000200006.
Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020;11(7):995–998. doi: 10.1021/acschemneuro.0c00122.
Song W-J, Hui CKM, Hull JH, Birring SS, McGarvey L, Mazzoneet SB, al. Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses. Lancet Respir Med. 2021;9(5):533–544. doi: 10.1016/S2213-2600(21)00125-9.
Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yanget L, al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18–22. doi: 10.1016/j.bbi.2020.03.031.
Bass DI, Meyer RM, Barros G, Carroll KT, Walker M, D'Oria M, et al. The impact of the COVID-19 pandemic on cerebrovascular disease. Semin Vasc Surg. 2021;34(2):20–27. doi: 10.1053/j.semvascsurg.2021.05.001.
Antoniello D, Milstein MJ, Dardick J, Fernandez-Torres J, Lu J, Patel N, et al. Altered mental status in COVID-19. J Neurol. 2021;269(1):12–18. DOI: 10.1007/s00415-021-10623-5.
Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol. 2020;19(5):383–384. doi: 10.1016/S1474-4422(20)30109-5.
Qin ES, Hough CL, Andrews J, Bunnell AE. Intensive care unit-acquired weakness and the COVID-19 pandemic: A clinical review. PM&R. 2022. doi:10.1002/pmrj.12757.
Lad H, Saumur TM, Herridge MS, Dos Santos CC, Mathur S, Batt J, et al. Intensive Care Unit-Acquired Weakness: Not Just Another Muscle Atrophying Condition. Int J Mol Sci. 2020;21(21):7840. doi: 10.3390/ijms21217840.
Claflin ES, Daunter AK, Bowman A, Startup J, Reed E, Krishnan C, et al. Hospitalized Patients With COVID-19 and Neurological Complications Experience More Frequent Decline in Functioning and Greater Rehabilitation Needs. Am J Phys Med Rehabil. 2021;100(8):725–729. doi: 10.1097/PHM.0000000000001807.
Alkeridy WA, Alanazy MH, Alamri N, Alqahtani A, Alhazzani A, Muayqil T. The Common Neurological Presentations and Clinical Outcomes of Coronavirus Disease 2019 in Saudi Arabia. Front Neurol. 2021;12:737328. doi: 10.3389/fneur.2021.737328.
Liotta EM, Batra A, Clark JR, Shlobin NA, Hoffman SC, Orban ZC, et al. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Ann Clin Transl Neurol. 2020;7(11):2221–2230. doi: 10.1002/acn3.51210.
Trigo J, García-Azorín D, Planchuelo-Gómez Á, Martínez-Pías E, Talavera B, Hernández-Pérez I, et al. Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study. J Headache Pain. 2020;21(1):94. doi: 10.1186/s10194-020-01165-8.
Tekin S, Ünlütürk Z, Erdoğan Ç, Bir LS, Sarı T, Uğurlu E. Neurological symptoms common in COVID-19 patients: A retrospective observational study. Acta Clin Croat. 2022;61(3):386–394. doi: 10.20471/acc.2022.61.03.03.
Rasouli S, Emami P, Azadmehr F, Karimyan F. Evaluating the frequency of neurological symptoms in COVID‐19 patients: A cross-sectional study. Health Sci Rep. 2023;6(7):e1400. doi: 10.1002/hsr2.1400.
Wesselingh R. Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review. Med J Aust. 2023;219(5):230–236. doi: 10.5694/mja2.52063.
Tyagi K, Rai P, Gautam A, Kaur H, Kapoor S, Suttee A, et al. Neurological manifestations of SARS-CoV-2: complexity, mechanism and associated disorders. Eur J Med Res. 2023;28:307. doi: 10.1186/s40001-023-01293-2.
Podury S, Srivastava S, Khan E et al. Relevance of CSF, Serum and Neuroimaging Markers in CNS and PNS Manifestation in COVID-19: A Systematic Review of Case Report and Case Series. Brain Sci. 2021;11(10):1354.
Garcia Elorrio E, Arrieta J, Arce H, Kakara M, Tandon M, Shrestha AK, et al. The COVID-19 pandemic: A call to action for health systems in Latin America to strengthen quality of care. Int J Qual Health Care. 2021;33(1):mzaa062. doi: 10.3390/brainsci11101354.
Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21. Lancet Lond Engl. 2022;399(10334):1513–1536. doi: 10.1016/S0140-6736(21)02796-3.
Mariños Sánchez E, Espino Alvarado P, Rodriguez L, Barreto-Acevedo E. [Neurological manifestations associated with COVID-19 in Edgardo Rebagliati Martins Hospital, Peru]. Rev Neuro-Psiquiatr. 2020;83(4):243–256. Doi: 10.20453/rnp.v83i4.3890.
Vences MA, Barreto-Acevedo E, Vences MA, Barreto-Acevedo E. [Atypical neuroimaging in patients with COVID-19 in Peru: case report]. Acta Médica Peru. 2020;37(4):484–489. Doi: 10.35663/amp.2020.374.1858.
Beghi E, Ivashynka A, Logroscino G, Ferreira de Oliveira F, Fleisher JE, Dumitrascu OM, et al. Pitfalls and biases in neuroepidemiological studies of COVID-19 and the nervous system: a critical appraisal of the current evidence and future directions. J Neurol. 2023;270(11):5162–5170. doi: 10.1007/s00415-023-11981-y.
Van Aerde N, Van den Berghe G, Wilmer A, Gosselink R, Hermans G. Intensive care unit acquired muscle weakness in COVID-19 patients. Intensive Care Med. 2020;46(11):2083–2085. doi: 10.1007/s00134-020-06244-7.
National Notifiable Diseases Surveillance System. US Center for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19). 2020 Interim Case Definition. 2020 [Cited 2021 Sep 28]. Available from: https://acortar.link/fxgEa0
Martínez-Chamorro E, Díez-Tascón A, Ibáñez-Sanz L, Ossaba-Vélez S, Borruel-Nacenta S. Radiologic diagnosis of patients with COVID-19. Radiologia. 2021;63(1):56–73. doi: 10.1016/j.rx.2020.11.001.
Desai I, Manchanda R, Kumar N, Tiwari A, Kumar M. Neurological manifestations of coronavirus disease 2019: exploring past to understand present. Neurol Sci. 2021;42(3):773–785. doi: 10.1007/s10072-020-04964-8.
Niazkar HR, Zibaee B, Nasimi A, Bahri N. The neurological manifestations of COVID-19: a review article. Neurol Sci. 2020;41(7):1667-1671. doi: 10.1007/s10072-020-04486-3.
Corona-Nakamura AL, Arias-Merino MJ, Morfín-Otero R, Rodriguez-Zavala G, León-Gil A, Camarillo-Escalera JR, et al. Neurological Manifestations and Complications of the Central Nervous System as Risk Factors and Predictors of Mortality in Patients Hospitalized with COVID-19: A Cohort Study. J Clin Med. 2023;12(12):4065. doi: 10.3390/jcm12124065.
Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45–e67. doi: 10.1164/rccm.201908-1581ST.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683–690. doi: 10.1001/jamaneurol.2020.1127.
Carod-Artal F. Neurological complications for coronavirus and COVID-19. Rev Neurol. 2020;70:311–22. doi: 10.33588/rn.7009.2020179.
Chou SH-Y, Beghi E, Helbok R, Moro E, Sampson J, Altamirano V, et al. Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19—A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open. 2021;4(5):e2112131. doi: 10.1001/jamanetworkopen.2021.12131.
Sampaio Rocha-Filho PA, Albuquerque PM, Carvalho LCLS, Dandara Pereira Gama M, Magalhães JE. Headache, anosmia, ageusia and other neurological symptoms in COVID-19: a cross-sectional study. J Headache Pain. 2022;23(1):2. doi: 10.1186/s10194-021-01367-8.
Gallo Marin B, Aghagoli G, Lavine K, Yang L, Siff EJ, Chiang SS, et al. Predictors of COVID-19 severity: A literature review. Rev Med Virol. 2021;31(1):e2146. doi: 10.1002/rmv.2146.
Veleri S. Neurotropism of SARS-CoV-2 and neurological diseases of the central nervous system in COVID-19 patients. Exp Brain Res. 2022;240(1):9–25. doi: 10.1007/s00221-021-06244-z.
Brown RL, Benjamin L, Lunn MP, Bharucha T, Zandi MS, Hoskote C, et al. Pathophysiology, diagnosis, and management of neuroinflammation in covid-19. BMJ. 2023;382:e073923. doi: 10.1136/bmj-2022-073923.
Hanganu A-R, Constantin A, Moise E-S, Niculae C-M, Olaru ID, Băicuș C, et al. Peripheral nervous system involvement associated with COVID-19. A systematic review of literature. PLOS ONE. 2023;18(4):e0283827. doi: 10.1371/journal.pone.0283827.
Ahmadi S, Khaledi S. Brain Renin–Angiotensin System: From Physiology to Pathology in Neuronal Complications Induced by SARS-CoV-2. Anal Cell Pathol Amst. 2023;2023:8883492. doi: 10.1155/2023/8883492.
Saleki K, Alijanizadeh P, Azadmehr A. Is neuropilin-1 the neuroimmune initiator of multi-system hyperinflammation in COVID-19? Biomed Pharmacother Biomedecine Pharmacother. 2023;167:115558. doi: 10.1016/j.biopha.2023.115558.
Taga A, Lauria G. COVID‐19 and the peripheral nervous system. A 2‐year review from the pandemic to the vaccine era. J Peripher Nerv Syst. 2022;27(1):4–30. doi: 10.1111/jns.12482.
Cagnazzo F, Arquizan C, Derraz I, Dargazanli C, Lefevre P-H, Riquelme C, et al. Neurological manifestations of patients infected with the SARS-CoV-2: a systematic review of the literature. J Neurol. 2021;268(8):2656–2665. doi: 10.1007/s00415-020-10285-9.
Topcuoglu MA, Pektezel MY, Oge DD, Bulut-Yüksel ND, Ayvacioglu C, Demirel E, et al. Stroke Mechanism in COVID-19 Infection: A Prospective Case-Control Study. J Stroke Cerebrovasc Dis. 2021;30(8):105919. doi: 10.1016/j.jstrokecerebrovasdis.2021.105919.
Desforges M, Le Coupanec A, Brison E, Meessen-Pinard M, Talbot PJ. Neuroinvasive and neurotropic human respiratory coronaviruses: potential neurovirulent agents in humans. Adv Exp Med Biol. 2014;807:75–96. doi: 10.1007/978-81-322-1777-0_6.
Jafari Khaljiri H, Jamalkhah M, Amini Harandi A, Pakdaman H, Moradi M, Mowla A. Comprehensive Review on Neuro-COVID-19 Pathophysiology and Clinical Consequences. Neurotox Res. 2021;39(5):1613–1629. doi: 10.1007/s12640-021-00389-z.
Frithiof R, Rostami E, Kumlien E, Virhammar J, Fällmar D, Hultströmet M, al. Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study. Clin Neurophysiol. 2021;132(7):1733–1740. doi: 10.1016/j.clinph.2021.03.016.
Sheikh AB, Chourasia PK, Javed N, Chourasia MK, Suriya SS, Upadhyay S, et al. Association of Guillain-Barre syndrome with COVID-19 infection: An updated systematic review. J Neuroimmunol. 2021;355:577577. doi: 10.1016/j.jneuroim.2021.577577.
Dalakas MC. Guillain-Barré syndrome: The first documented COVID-19–triggered autoimmune neurologic disease: More to come with myositis in the offing. Neurol - Neuroimmunol Neuroinflammation. 2020;7(5):e781. doi: 10.1212/NXI.0000000000000781.
Tankisi H. Critical illness myopathy and polyneuropathy in Covid-19: Is it a distinct entity? Clin Neurophysiol. 2021;132(7):1716–1717. doi: 10.1016/j.clinph.2021.04.001.
Yue T, Fan B, Zhao Y, Wilson Y, Du Z, Wang Q,et al. Dynamics of the COVID-19 basic reproduction numbers in different countries. Sci Bull. 2021;66(3):229–232. doi: 10.1016/j.scib.2020.10.008.
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Copyright (c) 2024 Luis Quispe-Moore, Miguel A. Vences, Victor Saquisela-Alburqueque, Elder Quispe-Huamani, Luis Cortez-Salazar, Wendy Seminario G., Mercedes Suarez-Loro, Enrique Portocarrero-Nieto, Carlos Alva-Diaz, Christoper A. Alarcon-Ruiz
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