Neurological manifestations and pathophysiological mechanisms of Covid-19
DOI:
https://doi.org/10.21270/archi.v10i7.5460Palabras clave:
Coronavirus Infections, Physiopathology, Neurologic ManifestationsResumen
Background - Severe acute respiratory syndrome coronavirus-2 is a novel, highly infectious coronavirus and the etiologic agent of Covid-19. The course of Covid-19 can range from mild flu-like symptoms to severe, life-threatening symptoms, especially when comorbidities are present. Increasing studies have reinforced the association between SARS-CoV-2 and various neurological manifestations, although the pathophysiological mechanisms remain uncertain. Objective - The aim of this paper was to briefly describe current findings on the relationship between SARS-CoV-2 pathophysiology and major CNS and Peripheral Nervous System (PNS) manifestations. Methods and Material - This work consists of a literature review based on the study of academic papers. To this end, the Pubmed platform was used to search for scientific articles, using the keywords: covid-19, coronavirus, physiopathology, neuronal symptoms. Results - out of 114,660 articles found, 94 were selected for this review. Conclusions - Periodic reviews collaborate in the constant updating and summarization of findings. Understanding the pathophysiology of SARS-CoV-2 on the SN and the link between the systems may lead to earlier and earlier diagnoses of neurological involvement, guide therapeutic management, prevent sequelae, and preserve lives.
Descargas
Citas
Zhou P, Yang X Lou, Wang XG, Hu B, Zhang L, Zhang W et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-73.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.
Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S et al. A novel coronavirus associated with severe acute respiratory syndrome.N Engl J Med.2003;348(20):1953-66.
Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y et al. From SARS to MERS, Thrusting Coronaviruses into the Spotlight. Viruses. 2019;11(1):59.
Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181-92.
Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-207.
Lake MA. What we know so far: COVID-19 current clinical knowledge and research. Clin Med (Lond). 2020;20(2):124-27.
Liu K, Chen Y, Lin R, Han K. Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. J Infect. 2020;80(6):e14-e18.
Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288(2):192-206.
Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: What we know. Int J Infect Dis. 2020;94:44-8.
Jordan RE, Adab P, Cheng KK. Covid-19: risk factors for severe disease and death. BMJ. 2020;368: m1198.
Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-5.
Mao L, Jin H, Wang M, Hu Y, Chen S, He et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683-90.
Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P et al. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe. 2020;;27(3):325-28.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-80.e8.
Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z et al. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell. 2020;181(4):894-904.e9.
Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87(5):E1-9.
Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002;532(1-2):107-10.
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-37.
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):995-98.
To KF, Lo AW. Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS-CoV) and its putative receptor, angiotensin-converting enzyme 2 (ACE2). J Pathol. 2004;203(3):740-43.
Chan PKS, To KF, Lo AWI, Cheung JLK, Chu I, Au FWL et al. Persistent infection of SARS coronavirus in colonic cells in vitro. J Med Virol. 2004;74(1):1-7.
Ding Y, Wang H, Shen H, Li Z, Geng J, Han H et al. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol. 2003;200(3):282-89.
Gu J, Gong E, Zhang B, Zheng J, Gao Z, Zhong Y et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202(3):415-24.
Eberhardt KA, Meyer-Schwickerath C, Heger E, Knops E, Lehmann C, Rybniker J et al. RNAemia Corresponds to Disease Severity and Antibody Response in Hospitalized COVID-19 Patients. Viruses. 2020;12(9):1045.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-18.
Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007;7(10):803-15.
Erickson MA, Banks WA. Neuroimmune axes of the blood-brain barriers and blood-brain interfaces: bases for physiological regulation, disease states, and pharmacological interventions. Pharmacol Rev. 2018;70(2):278-314.
Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82(15):7264-75.
Dubé M, Le Coupanec A, Wong AHM, Rini JM, Desforges M, Talbot PJ. Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43. J Virol. 2018;92(17):e00404-18.
Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Sci Adv. 2020;6(31):eabc5801.
Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18-22.
Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun. 2020;88:945-6.
Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020;94:55-8.
Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T et al. Encephalopathy and encephalitis associated with cerebrospinal fluid cytokine alterations and coronavirus disease, Atlanta, Georgia, USA, 2020. Emerg Infect Dis. 2020;26(9):2016-21.
Slooter AJC, Otte WM, Devlin JW, Arora RC, Bleck TP, Claassen J et al. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med. 2020;46(5):1020-22.
Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-70.
Maas MB. Critical Medical Illness and the Nervous System. Continuum (Minneap Minn). 2020;26(3):675-94.
Tan YK, Goh C, Leow AST, Tambyah PA, Ang A, Yap ES et al. COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature. J Thromb Thrombolysis. 2020;50(3):587-95.
Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med. 2020;382(17):e38.
Becker RC. COVID-19 update: Covid-19-associated coagulopathy. J Thromb Thrombolysis. 2020;50(1):54-67.
Mucha SR, Dugar S, McCrae K, Joseph DE, Bartholomew J, Sacha G et al. Coagulopathy in COVID-19: Manifestations and management. Cleve Clin J Med. 2020;87(8):461-68.
Lippi G, Favaloro EJ. D-dimer is Associated with Severity of Coronavirus Disease 2019: A Pooled Analysis. Thromb Haemost. 2020; 120(5):876-78.
Borges do Nascimento IJ, Cacic N, Abdulazeem HM, von Groote TC, Jayarajah U, Weerasekara I, et al. Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis. J Clin Med. 2020;9(4):941.
Belvis R. Headaches During COVID-19: My clinical case and review of the literature. Headache. 2020;60(7):1422-26.
Toptan T, Aktan Ç, Başarı A, Bolay H. Case Series of Headache Characteristics in COVID-19: Headache Can Be an Isolated Symptom. Headache. 2020;60(8):1788-92.
Poncet-Megemont L, Paris P, Tronchere A, Salazard J-P, Pereira B, Dallel R et al. High Prevalence of Headaches During Covid-19 Infection: A Retrospective Cohort Study. Headache. 2020;60(10):2578-82.
Sampaio Rocha-Filho PA, Voss L. Persistent Headache and Persistent Anosmia Associated With COVID-19. Headache. 2020;60(8):1797-9.
Bolay H, Gül A, Baykan B. COVID-19 is a Real Headache! Headache. 2020;60(7):1415-21.
Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93(1):250-56.
Sun J, Xiao J, Sun R, Tang X, Liang C, Lin H et al. Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. Emerg Infect Dis. 2020; 26(8):1834-38.
Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology. 2020;58(3):299-301.
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251-261.
Kaye R, Chang CWD, Kazahaya K, Brereton J, Denneny JC 3rd. COVID-19 Anosmia Reporting Tool: Initial Findings. Otolaryngol Head Neck Surg. 2020;163(1):132-34.
Zang Y, Han P, Burghardt S, Knaapila A, Schriever V, Hummel T. Influence of olfactory dysfunction on the perception of food. Eur Arch Otorhinolaryngol. 2019;276(10):2811-7.
Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8.
Shors AR. Herpes zoster and severe acute herpetic neuralgia as a complication of COVID-19 infection. JAAD Case Rep. 2020;6(7):656-7.
Ferreira ACA d. F, Romão TT, Macedo YS, Pupe C, Nascimento OJM. COVID-19 and herpes zoster co-infection presenting with trigeminal neuropathy. Eur J Neurol. 2020; 27(9):1748-50.
Aksan F, Nelson EA, Swedish KA. A COVID-19 patient with intense burning pain. J Neurovirol. 2020;26(5):800-1.
Le Balc'h P, Pinceaux K, Pronier C, Seguin P, Tadié JM, Reizine F. Herpes simplex virus and cytomegalovirus reactivations among severe COVID-19 patients. Crit Care. 2020;24(1):530.
Kennedy PG, Rovnak J, Badani H, Cohrs RJ. A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation. J Gen Virol. 2015;96(Pt 7):1581-602.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
Wong AM, Simon EM, Zimmerman RA, Wang HS, Toh CH, Ng SH. Acute necrotizing encephalopathy of childhood: correlation of MR findings and clinical outcome. AJNR Am J Neuroradiol. 2006;27(9):1919-23.
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: Imaging Features. Radiology. 2020;296(2): E119-E20.
Dixon L, Varley J, Gontsarova A, Mallon D, Tona F, Muir D et al. COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e789.
Virhammar J, Kumlien E, Fällmar D, Frithiof R, Jackmann S, Sköld MK et al. Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid. Neurology. 2020;95(10):445-49.
Pohl D, Alper G, Van Haren K, Kornberg AJ, Lucchinetti CF, Tenembaum S, et al. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome. Neurology. 2016;87(9 Suppl 2):S38-45.
Reichard RR, Kashani KB, Boire NA, Constantopoulos E, Guo Y, Lucchinetti CF. Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathol. 2020;140(1):1-6.
Zhang T, Hirsh E, Zandieh S, Rodricks MB. COVID-19-Associated Acute Multi-infarct Encephalopathy in an Asymptomatic CADASIL Patient. Neurocrit Care. 2020:1-4.
Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al. Diagnosis and management of Guillain-Barré syndrome in ten steps. Nat Rev Neurol. 2019;15(11):671-83.
Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG et al. Guillain-Barré Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020;382(26):2574-76.
Juliao Caamaño DS, Alonso Beato R. Juliao Caamaño DS, Alonso Beato R. Facial diplegia, a possible atypical variant of Guillain-Barré Syndrome as a rare neurological complication of SARS-CoV-2. J Clin Neurosci. 2020;77:230-32.
Chan JL, Ebadi H, Sarna JR. Guillain-Barré Syndrome with Facial Diplegia Related to SARS-CoV-2 Infection. Can J Neurol Sci. 2020;47(6):852-54.
Wakerley BR, Uncini A, Yuki N. Guillain-Barré and Miller Fisher syndromes--new diagnostic classification. Nat Rev Neurol. 2014;10(9):537-44.
Gutiérrez-Ortiz C, Méndez-Guerrero A, Rodrigo-Rey S, San Pedro-Murillo E, Bermejo-Guerrero L, Gordo-Mañas R et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020;95(5):e601-e5.
Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Bradley Segal J et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr. 2020;10(6):537-40.
Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110(17):2747-71.
Burns JC, Herzog L, Fabri O, Tremoulet AH, Rodó X, Uehara R et al. Seasonality of Kawasaki disease: a global perspective. PLoS One. 2013;8(9):e74529.
Ouldali N, Pouletty M, Mariani P, Beyler C, Blachier A, Bonacorsi S et al. Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic: a time-series analysis. Lancet Child Adolesc Health. 2020;4(9):662-68.
Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395(10239):1771-78.
Pouletty M, Borocco C, Ouldali N, Caseris M, Basmaci R, Lachaume N et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort. Ann Rheum Dis. 2020;79(8):999-1006.
Lake BB, Chen S, Sos BC, Fan J, Kaeser GE, Yung YC, et al. Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain. Nat Biotechnol. 2018;36(1):70-80.
Teuwen L-A, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020;20(7):389-91.
Azizi SA, Azizi SA. Neurological injuries in COVID-19 patients: direct viral invasion or a bystander injury after infection of epithelial/endothelial cells. J Neurovirol. 2020;26(5):631-41.
Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74.
Steardo L, Steardo L Jr, Zorec R, Verkhratsky A. Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19. Acta Physiol (Oxf). 2020;229(3):e13473.
Niazkar HR, Zibaee B, Nasimi A, Bahri N. The neurological manifestations of COVID-19: a review article. Neurol Sci. 2020;41(7):1667-71.
Sankowski R, Mader S, Valdés-Ferrer SI. Systemic inflammation and the brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration. Front Cell Neurosci. 2015;9:28.
Garg RK. Spectrum of Neurological Manifestations in Covid-19: A Review. Neurol India. 2020;68(3):560-72.