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Analisar os aspectos imunopatológicos associados à infecção pelo SARS-CoV-2, além de discutir as potenciais ferramentas terapêuticas direcionadas aos componentes imunológicos. Método: Trata-se de uma revisão bibliográfica, com buscas realizadas na base de dados PubMed. Foram definidos critérios de inclusão para artigos que investigassem diretamente a resposta imunológica e inflamatória à infecção pelo SARS-CoV-2, excluindo revisões, artigos em idiomas diferentes do inglês e aqueles não relacionados ao sistema imunológico ou à resposta inflamatória. Após uma busca inicial, 735 artigos foram identificados e submetidos a uma triagem com base nos critérios estabelecidos. Ao final , 65 artigos foram selecionados para a revisão final. Resultados: O estudo revelou que os níveis de LDH e PCR diminuíram durante a hospitalização, enquanto a contagem de neutrófilos diminuiu nos pacientes críticos, indicando uma mudança na resposta imunológica. Diversas abordagens terapêuticas, como anticorpos monoclonais e células mesenquimais, foram exploradas para modular a resposta inflamatória, apesar das limitações logísticas e de disponibilidade. Conclusão: São necessários mais estudos para entender o comportamento do SARS-CoV-2 em pacientes graves e suas mutações, visando abordagens terapêuticas baseadas em evidências científicas.
Este artigo tem por objetivo realizar uma abordagem abrangente dos aspectos imunopatológicos associados à infecção pelo SARS-CoV-2, discutindo, além disso, as possíveis ferramentas terapêuticas direcionadas aos componentes imunológicos. Foi utilizado como motor de busca a base de dados PubMed para seleção dos artigos, através dos descritores "SARS-CoV-2", "Coronavírus", "COVID-19" e "immune response", "immunity", "immunological markers", "inflammation", "Inflammatory response". Conclui-se que, a partir do estudo da imunologia do SARS-CoV-2, o uso de anticorpos monoclonais, células mesenquimais e outros tratamentos abordados são efetivos em pacientes críticos com o vírus, apesar de desafios logísticos e de disponibilidade.
Referências
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W. A Novel Coronavirus from Patients with Pneumonia in China. N Engl J Med. 2020 Feb 20;382(8):727-733.
Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, Pan P, Wang W, Hu D, Liu X, Zhang Q, Wu J. Coronavirus infections and immune responses. J Med Virol. 2020 Apr;92(4):424-432.
Azkur AK, Akdis M, Azkur D, Sokolowska M, van de Veen W, Brüggen MC, O'Mahony L, Gao Y, Nadeau K, Akdis CA. Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy. 2020 Jul;75(7):1564-1581.
Yang M. Cell Pyroptosis, a Potential Pathogenic Mechanism of 2019-nCoV Infection. SSRN Journal. 2020.
Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, Kritas SK. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVID-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020 March-April;34(2):327-331.
Siu KL, Kok KH, Ng MJ, Poon VKM, Yuen KY, Zheng BJ, Jin DY. Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex. J Biol Chem. 2009 Jun 12;284(24):16202-16209.
Liu F, Li L, Xu M, Wu J, Luo D, Zhu Y, Li B, Song X, Zhou X. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020 Jun;127:104370.
Bolondi G, Russo E, Gamberini E, Circelli A, Meca MCC, Brogi E, Viola L, Bissoni L, Poletti V, Agnoletti V. Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study. World J Emerg Surg. 2020 Jun 30;15(1):41.
Barrios-López JM, Rego-García I, Muñoz Martínez C, Romero-Fábrega JC, Rivero Rodríguez M, Ruiz Giménez JA, Escamilla-Sevilla F, Mínguez-Castellanos A, Fernández Pérez MD. Ischaemic stroke and SARS-CoV-2 infection: A causal or incidental association? Neurologia (Engl Ed). 2020 Jun;35(5):295-302.
Hantoushzadeh S, Norooznezhad AH. Possible Cause of Inflammatory Storm and Septic Shock in Patients Diagnosed with (COVID-19). Arch Med Res. 2020 May;51(4):347-348.
Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, Newburger JW, Kleinman LC, Heidemann SM, Martin AA, Singh AR, Li S, Tarquinio KM, Jaggi P, Oster ME, Zackai SP, Gillen J, Ratner AJ, Walsh RF, Fitzgerald JC, Keenaghan MA, Alharash H, Doymaz S, Clouser KN, Giuliano JS Jr, Gupta A, Parker RM, Maddux AB, Havalad V, Ramsingh S, Bukulmez H, Bradford TT, Smith LS, Tenforde MW, Carroll CL, Riggs BJ, Gertz SJ, Daube A, Lansell A, Coronado Munoz A, Hobbs CV, Marohn KL, Halasa NB, Patel MM, Randolph AG; Overcoming COVID-19 Investigators; CDC COVID-19 Response Team. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 2020 Jul 23;383(4):334-346.
Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, Barranco MA, Maxted AM, Rosenberg ES, Easton D, Udo T, Kumar J, Pulver W, Smith L, Hutton B, Blog D, Zucker H; New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med. 2020 Jul 23;383(4):347-358.
Klocperk A, Parackova Z, Dissou J, Malcova H, Pavlicek P, Vymazal T, Dolezalova P, Sediva A. Case Report: Systemic Inflammatory Response and Fast Recovery in a Pediatric Patient With COVID-19. Front Immunol. 2020 Jul 3;11:1665.
Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Jul;75(7):1730-1741.
Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-768.
Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, Wang X, Hu C, Ping R, Hu P, Li T, Cao F, Chang C, Hu Q, Jin Y, Xu G. Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study. Am J Respir Crit Care Med. 2020 Jun 1;201(11):1372-1379.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult in-patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062.
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629.
Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair C, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020 Jun 4;5(11):e138999.
Porto BN, Stein RT. Neutrophil Extracellular Traps in Pulmonary Diseases: Too Much of a Good Thing? Front Immunol. 2016 Aug 15;7:311.
Liu J, Wu P, Gao F, Qi J, Kawana-Tachikawa A, Xie J, Vavricka CJ, Iwamoto A, Li T, Gao GF. Novel immunodominant peptide presentation strategy: a featured HLA-A*2402-restricted cytotoxic T-lymphocyte epitope stabilized by intrachain hydrogen bonds from severe acute respiratory syndrome coronavirus nucleocapsid protein. J Virol. 2010 Nov;84(22):11849-57.
Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, Thompson RF. Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2. J Virol. 2020 Jun 16;94(13):e00510-20.
Poh CM, Carissimo G, Wang B, Amrun SN, Lee CYP, Chee RSL, Fong SW, Yeo NKW, Lee WH, Torres-Ruesta A, Leo YS, Chen MIC, Tan SY, Chai LYA, Kalimuddin S, Kheng SSG, Thien SY, Young BE, Lye DC, Hanson BJ, Wang CI, Renia L, Ng LFP. Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients. Nat Commun 11, 2806 (2020).
Seydoux E, Homad LJ, MacCamy AJ, Parks KR, Hurlburt NK, Jennewein MF, Akins NR, Stuart AB, Wan YH, Feng J, Whaley RE, Singh S, Boeckh M, Cohen KW, McElrath MJ, Englund JA, Chu HY, Pancera M, McGuire AT, Stamatatos L. Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation. Immunity. 2020 Jul 14;53(1):98-105.e5.
Xie L, Wu Q, Lin Q, Liu X, Lin W, Hao S, Hu W, Xiang G, Lu H, Li S. Dysfunction of adaptive immunity is related to severity of COVID-19: a retrospective study. Ther Adv Respir Dis. 2020 Jan-Dec;14: 1–15.
Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-768.
Chen RF, Chang JC, Yeh WT, Lee CH, Liu JW, Eng HL, Yang KD. Role of vascular cell adhesion molecules and leukocyte apoptosis in the lymphopenia and thrombocytopenia of patients with severe acute respiratory syndrome (SARS). Microbes Infect. 2006 Jan;8(1):122-7.
Fragoso-Saavedra S, Iruegas-Nunez DA, Quintero-Villegas A, García-González HB, Nuñez I, Carbajal-Morelos SL, Audelo-Cruz BM, Arias-Martínez S, Caro-Vega Y, Calva JJ, Luqueño-Martínez V, González-Duarte A, Crabtree-Ramírez B, Crispín JC, Sierra-Madero J, Belaunzarán-Zamudio PF, Valdés-Ferrer SI. A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol. BMC Infect Dis. 2020 Oct 16;20(1):765.
Kyriazopoulou E, Panagopoulos P, Metallidis S, Dalekos GN, Poulakou G, Gatselis N, Karakike E, Saridaki M, Loli G, Stefos A, Prasianaki D, Georgiadou S, Tsachouridou O, Petrakis V, Tsiakos K, Kosmidou M, Lygoura V, Dareioti M, Milionis H, Papanikolaou IC, Akinosoglou K, Myrodia DM, Gravvani A, Stamou A, Gkavogianni T, Katrini K, Marantos T, Trontzas IP, Syrigos K, Chatzis L, Chatzis S, Vechlidis N, Avgoustou C, Chalvatzis S, Kyprianou M, van der Meer JW, Eugen-Olsen J, Netea MG, Giamarellos-Bourboulis EJ. An open label trial of anakinra to prevent respiratory failure in COVID-19. Elife. 2021 Mar 8;10:e66125.
Cai S, Sun W, Li M, Dong L. A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab. Clin Rheumatol. 2020 Sep;39(9):2797-2802.
Dastan F, Nadji SA, Saffaei A, Tabarsi P.Tocilizumab administration in a refractory case of COVID-19. Int J Antimicrob Agents. 2020;56(2):106043‐106044
Tian J, Zhang M, Jin M, Zhang F, Chu Q, Wang X, Chen C, Yue H, Zhang L, Du R, Zhao D, Zeng Z, Zhao Y, Liu K, Wang M, Hu K, Miao X, Zhang H. Repurposed Tocilizumab in Patients with Severe COVID-19. J Immunol. 2021 Feb 1;206(3):599-606.
Generali D, Bosio G, Malberti F, Cuzzoli A, Testa S, Romanini L, Fioravanti A, Morandini A, Pianta L, Giannotti G, Viola EM, Giorgi-Pierfranceschi M, Foramitti M, Tira RA, Zangrandi I, Chiodelli G, Machiavelli A, Cappelletti MR, Giossi A, De Giuli V, Costanzi C, Campana C, Bernocchi O, Sirico M, Zoncada A, Molteni A, Venturini S, Giudici F, Scaltriti M, Pan A. Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study. Int J Infect Dis. 2021 Mar;104:433-440.
Meng F, Xu R, Wang S, Xu Z, Zhang C, Li Y, Yang T, Shi L, Fu J, Jiang T, Huang L, Zhao P, Yuan X, Fan X, Zhang JY, Song J, Zhang D, Jiao Y, Liu L, Zhou C, Maeurer M, Zumla A, Shi M, Wang FS. Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial. Signal Transduct Target Ther. 2020 Aug 27;5(1):172.
Zhang Y, Ding J, Ren, S, Wang W, Yang Y, Li S, Meng M, Wu T, Liu D, Tian H, Chen S, Zhou C. Intravenous infusion of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells as a potential treatment for patients with COVID-19 pneumonia. Stem Cell Res Ther. 2020 May. 11, 207.
Liang B, Chen J, Li T, Wu H, Yang W, Li Y, Li J, Yu C, Nie F, Ma Z, Yang M, Xiao M, Nie P, Gao Y, Qian C, Hu M. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report. Medicine (Baltimore). 2020 Jul 31;99(31):e21429.
Saleh M, Vaezi AA, Aliannejad R, Sohrabpour AA, Kiaei SZF, Shadnoush M, Siavashi V, Aghaghazvini L, Khoundabi B, Abdoli S, Chahardouli B, Seyhoun I, Alijani N, Verdi J. Cell therapy in patients with COVID-19 using Wharton's jelly mesenchymal stem cells: a phase 1 clinical trial. Stem Cell Res Ther. 2021 Jul 16;12(1):410.
Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589.
Im JH, Nahm CH, Baek JH, Kwon HY, Lee JS. Convalescent Plasma Therapy in Coronavirus Disease 2019: a Case Report and Suggestions to Overcome Obstacles. J Korean Med Sci. 2020 Jul 6;35(26):e239.
Díaz F, Cores C, Atenas O, Rodríguez N, Bustos R, Cruces P. Rationale of Therapeutic Plasma Exchange as Rescue Immunomodulatory Treatment for MIS-C With Multiorgan Failure. Pediatr Infect Dis J. 2021 Jul 1;40(7):e259-e262.
Song NJ, Allen C, Vilgelm AE, Riesenberg BP, Weller KP, Reynolds K, Chakravarthy KB, Kumar A, Khatiwada A, Sun Z, Ma A, Chang Y, Yusuf M, Li A, Zeng C, Evans JP, Bucci D, Gunasena M, Xu M, Liyanage NPM, Bolyard C, Velegraki M, Liu SL, Ma Q, Devenport M, Liu Y, Zheng P, Malvestutto CD, Chung D, Li Z. Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology. J Hematol Oncol. 2022 Jan 10;15(1):5.
Rizvi S, Danic M, Silver M, LaBond V. Cytosorb filter: An adjunct for survival in the COVID-19 patient in cytokine storm? a case report. Heart Lung. 2021 Jan-Feb;50(1):44-50.
Selzman CH, Tonna JE, Pierce J, Vargas C, Skidmore C, Lewis G, Hatton ND, Phillips JD. A pilot trial of human amniotic fluid for the treatment of COVID-19. BMC Res Notes. 2021 Jan 22;14(1):32.
Mitrani MI, Bellio MA, Meglin A, Khan A, Xu X, Haskell G, Arango A, Shapiro GC. Treatment of a COVID-19 long hauler with an amniotic fluid-derived extracellular vesicle biologic. Respir Med Case Rep. 2021;34:101502.
Bellio MA, Bennett C, Arango A, Khan A, Xu X, Barrera C, Friedewald V, Mitrani MI. Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection. Biomater. Biosyst. 2021; 4, 100031.
Xie L, Wu Q, Lin Q, Liu X, Lin W, Hao S, Hu W, Xiang G, Lu H, Li S. Dysfunction of adaptive immunity is related to severity of COVID-19: a retrospective study. Ther Adv Respir Dis. 2020 Jan-Dec;14:1-15.
Roncati L, Ligabue G, Fabbiani L, Malagoli C, Gallo G, Lusenti B, Nasillo V, Manenti A, Maiorana A. Type 3 hypersensitivity in COVID-19 vasculitis. Clin Immunol. 2020 Aug;217:108487.
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