Fisiopatología del daño multiorgánico en la infección por SARS-Cov2
Resumen
La glucoproteína S del SARS-CoV-2 se une a la enzima convertidora de la angiotensina 2 (ACE2). El genoma del virus codifica cuatro proteínas estructurales esenciales: glucoproteína espiga, proteína de envoltura pequeña, proteínas matrices y proteína de nucleocápside. Se expresa más en hombres, quizá por el estradiol y la testosterona. En la viremia pasa de las glándulas salivales y membranas mucosas, especialmente nasal y laringe, a los pulmones y a otros órganos con los mismos receptores ACE2: corazón, hígado e, incluso, al sistema nervioso central; llega a los intestinos, lo que puede explicar los síntomas ; se detecta en las heces desde el inicio de la infección.
La coexistencia de hipertensión arterial sistémica, diabetes mellitus o neumopatías crónicas, obesidad o tabaquismo, inmunodeficiencias y la senescencia son clave en la patogénesis viral. Cuando el sistema inmunológico es ineficiente en controlar efectivamente al virus en la fase aguda, puede evolucionar a un síndrome de activación de macrófagos que da pie a la temida tormenta de citocinas que pone al paciente en un estado crítico.
Entender la fisiopatogenia de la infección por SARS-CoV-2 es la piedra angular para establecer el diagnóstico oportuno e implementar el tratamiento adecuado y limitar la propagación del virus y, en última instancia, eliminarlo.
Citas
Haibo Zhang H, et al. Angiotensin‑converting enzyme 2(ACE2) as a SARS‑CoV‑2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 2020;46:586–590 https://doi.org/10.1007/s00134-020-05985-9
Guo Y et al. The origin, transmission and clinical therapies on coronavirus disease 2019(COVID-19)
outbreak – an update on the Status. Military Medical Research 2020;7:11
https://doi.org/10.1186/s40779-020-00240-0)
SolerMJ,et al. Enzima conversiva de la angiotensina 2 y su papel emergente en la regulación del sistema renina-angiotensina. Med Clin (Barc) 2008;131(6):230-
Malavazos A, et al. .Targeting the adipose tissue in Covid 19. Obesity. doi: 10.1002 / oby.22844
Cai G. Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov. medRxiv 2020; DOI:10.1101/2020.02.05.20020107 (preprint).
Wang J, et al. The Potential for Antibody-Dependent Enhancement of SARS-CoV-2 Infection: Translational Implications for Vaccine Development. DOI: 10.1017 /cts.2020.39
Watkins J. Preventingacovid-19 pandemics. BMJ 2020;368 doi: https://doi.org/10.1136/bmj.m810
Landazuri P, Granobles C, Loango N.Diferencias entre los Sexos en la Actividad de la Enzima Conversora de la Angiotensina y en la Presión Arterial en Niños: un Estudio Observacional Arq Bras Cardiol 2008; 91(6) : 17-23
Bouman, A, et al. Sex hormones and the immune response in humans. Human Reproduction Update 2005; 11(4), 411-423. https://doi.org/10.1093/humupd/dmi008
Zhang H, et al. Angiotensin converting enzyme 2 (ACE2) as a SARS-CoV2 receptor: molecular
mechanisms and potential therapeutic target. Intensive Care Med 2020: 46:586–590
https://doi.org/10.1007/s00134-020-05985-9
Channappanavar R, et al. T cell-mediated immune response to respiratory coronaviruses, Immunol Res 2014; 59:118–128
Cervantes B , et al. Type I IFN-mediated protection of macrophages and dendritic cells secures control of murine coronavirus infection. J Immunol 2009;182:1099 –1106
Cameron MJ, et al. Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory Syndrome. J Virol 2007;81: 8692 – 8706
Fink SL et al. Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells. Infect Immun 2005; 73: 1907-1916
Mali SN, et al. The Rise of New Coronavirus Infection (COVID-19): A Recent Update and Potential Therapeutic Candidates. EJMO 2020; 4(1):35–41.
Xu, Z. et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Medicin 2020; 8 : 420-422 DOI:https://doi.org/10.1016/S2213-2600(20)30076-X
Bonanad C, et al. Coronavirus: the geriatric emergency of 2020. Joint document of the Section on Geriatric Cardiology of the Spanish Society of Cardiology and the Spanish Society ofGeriatrics and Gerontology. Rev Esp Cardiol (English Edition (2020),doi:https://doi.org/10.1016/j.rec.2020.05.001
Kam KQ , et al. A well infant with coronavirus disease 2019 (COVID-19) with high viral load. Clin Infect Dis. 2020;ciaa201. doi:10.1093/cid/ciaa201
Dong Y, et al. Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China. Pediatrics 2020 Mar 16. pii: e20200702. doi: 10.1542/peds.2020-0702.
Gu, J. et al. Multiple organ infection and the pathogenesis of SARS. J Exp Medicin 2005; 202: 415-424
Cheung, CY et al. Cytokine Responses in Severe Acute Respiratory Syndrome Coronavirus-Infected Macrophages In Vitro: Possible Relevance to Pathogenesis. J Virol 2005; 79, 7819-7826.
Yilla, M. y col. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res 2005; 107 :93-101
Faraha GA, et al. Increased expression of CD8 marker on T-cells in COVID-19 patients Blood Cells Mol Dis. 2020. Apr 13;83:102437. doi: 10.1016/j.bcmd.2020.102437. [Epub ahead of print]
García-Salido A, Revisión Narrativa Sobre La Respuesta Inmunitaria Frente A Coronavirus: Descripción General, Aplicabilidad Para Sars-Cov2 e Implicaciones Terapéuticas, Anales de Pediatria(2020), doi:https://doi.org/10.1016/j.anpedi.2020.04.
Geng Li, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92:424–432.
Wu D , et al. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. Journal of Microbiology, Immunology and Infection, https://doi.org/10.1016/j.jmii.2020.03.005
Maloir Q, et al. Acute respiratory distress revealing antisynthetase síndrome. Rev Med Liege 2018;73(7‐8):370‐375.
Ow Ng, et al. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post‐infection. Vaccine 2016; 34(17):2008‐2014.
Zhao J , et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019, Clinical Infectious Diseases 2020, ciaa344. https://doi.org/10.1093/cid/ciaa344
Xiao T, et al. Profile of Specific Antibodies to SARS-CoV-2: The First Report. J Infection 2020, doi: https://doi.org/10.1016/j.jinf.2020.03.012)
Ho MS , et al. Neutralizing Antibody Response and SARS Severity. Emerg Infect Dis 2005;11: 1730 – 1737
Lu R , et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 20:30251 – 30258 pii: S0140-6736
Chen, IY, et al. Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome. Front Microbiol. 2019 Jan 29;10:50. doi: 10.3389/fmicb.2019.00050. eCollection 2019.
Metha P, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2010; 395:1033-34 https://doi.org/10.1016/ S0140-6736(20)30630-9
Chan, JF et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster Lancet 2020; 395: 514–523
Moore JB, et al. Cytokine release syndrome in severe COVID-19 Science 2020;368:473-474 DOI: 10.1126/science.abb8925
Pacha, O., Sallman, M.A. & Evans, S.E. COVID-19: a case for inhibiting IL-17?. Nat Rev Immunol (2020). https://doi.org/10.1038/s41577-020-0328-z
Respuesta Inmune Trombótica Asociada a Covid-19 Modificado de (RITAC) Gauna M https://fundacionio.com/wp-content/uploads/2020/04/Si%CC%81ndrome RITAC.pdf.pdf.pdf.pdf.pdf.pdf.pdf
McGonagle D, et al. Interleukin-6 use in COVID-19 pneumonia related macrophage activation syndrome Autoimmunity Reviews 2020. https://doi.org/10.1016/j.autrev.2020.102537
Wang WK, et al. Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis. Emerg Infect Dis 2004;10(7):1213–1219.
Sims AC, et al. Severe Acute Respiratory Syndrome Coronavirus Infection of Human Ciliated Airway Epithelia: Role of Ciliated Cells in Viral Spread in the Conducting Airways of the Lungs J Virol 2005; 79: 155111-15524
Ling Lin, et al. Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia. Emerging Microbes & Infections 2020;9:727-732, DOI: 10.1080/22221751.2020.1746199
Zhou, F, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort Study. Lancet 2020; 395: 1054-1062.
Liao M, et al. The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing. Preimpression en medRxiv 2020. https://doi.org/10.1101/2020.02.23.20026690.
Zhou, Y. et al. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Natl Sci Rev 2020. https://doi.org/10.1093/nsr/nwaa041.
Carolyn M, et al. MD1 Viral Pathogens and Acute Lung Injury: Investigations Inspired by the SARS Epidemic and the 2009 H1N1 Influenza. Semin Respir Crit Care Med 2013;34:475–486.
Gu J, Han B, Wang J. COVID-19: COVID-19: Gastrointestinal Manifestations and Potential Fecal–Oral Transmission. Gastroenterology 2020 Mar 3. doi: 10.1053/j.gastro.2020.02.054.
Xiao F, et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 3 Mar 2020:S0016-5085(20)30282-1. doi: 10.1053/j.gastro.2020.02.055. PMID: 3214277.
Yeo C, et al. Enteric involvement of coronaviruses: is faecal–oral transmission of SARS CoV-2 possible? Lancet Gastroenterol Hepatol. 2020 doi: 10.1016/S2468-1253(20)30048-0. published online Feb 19
Chai X, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv. 2020 doi: 10.1101/2020.02.03.931766. published online Feb 4. (preprint)
Xu Z, et al. Pathological findings of COVID-19 associated with acute respiratory distress
syndrome. Lancet Respir Med. 2020 doi: 10.1016/S2213-2600(20)30076-X. published online
Zhang C, Shi L, Wang FS. Liver injury in COVID-19: Management and challenges. Lancet Gastroenterol Hepatol 2020 Mar 4. doi: 10.1016/S2468-1253(20)30057-1.
Shaobo Shi, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With
COVID19 in Wuhan, China JAMA Cardiol 2020. doi:10.1001/jamacardio.2020.0950
Xu D, et al. Identification of a Potential Mechanism of Acute Kidney Injury During theCovid-19
Outbreak: A Study Base don Single Cell Transcriptome Analysis Preprints 2020 2020020331.
Cheng Y,Luo R,Wang K et al. Kidney impairment is associated with inhospitaldeath of Covid-1
patients medRxiv 2020 https://doi.org/10.1101/2020.02.18.20023242.
WangT,Du Z,Zhu F et al. Comorbidities and multi-organ injuries in the treatment of COVID-19
The Lancet 2020; 395:10228 Doi: https://doi.org/101016/S0140- 6736(20)30558-4
Diao B,Wang C,Wang R et al. Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) infection medRxiv 2020 Doi: https://doi.org/10.1101/2020.03.04.20031120
Mannan B A et al. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host−Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci 2020; 11: 995−998
Liu W; Li H COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism ChemRxiv 2020. Preimpresión https://doi.org/10.26434/chemrxiv.11938173.v7
