La respuesta inmune frente a SARS-CoV-2, ¿un arma de doble filo?

Autores/as

  • José Alcamí Pertejo Instituto de Salud Carlos III

DOI:

https://doi.org/10.37536/RIECS.2020.5.1.212

Palabras clave:

SARS-CoV-2, COVID-19, Coronavirus, Tormenta de citocinas, Interferón, Anticuerpos neutralizantes, Vacunas

Resumen

La pandemia por el nuevo coronavirus, SARS-CoV-2, ha provocado más de 350.000 muertes en el mundo. En este artículo se revisan los principales mecanismos de respuesta inmune frente a la infección por SARS-CoV-2. Todavía no disponemos de un cuadro completo de la enfermedad, sus mecanismos patogénicos y las respuestas inmunes protectoras. Los datos publicados sugieren que las respuestas mediadas por interferón clase I en las fases iniciales probablemente son el principal mecanismo de control de la infección por la inmunidad innata. Una vez que las respuestas adaptativas se producen, la síntesis de anticuerpos IgG con capacidad neutralizante son el principal mecanismo de curación, sin que podamos excluir una acción complementaria de las respuestas celulares, CD4, CD8 y NK. En un porcentaje del 10-20% de pacientes que desarrollan síntomas se produce un cuadro inflamatorio masivo de tormenta de citocinas y trastornos de la coagulación que agravan la enfermedad y ensombrecen el pronóstico de los pacientes infectados por SARS-CoV-2.

Citas

Coronavirus Host Range Expansion and Middle East Respiratory Syndrome Coronavirus Emergence: Biochemical Mechanisms and Evolutionary Perspectives. Peck KM et al. Annu. Rev. Virol. 2015. 2:95–117. doi: 10.1146/annurev-virology-100114-055029

The hallmarks of COVID-19 disease. Tang D et al. PLoS Pathog 16(5):e1008536. https://doi.org/10.1371/journal.ppat.1008536

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Menachery VD et al. Nat. MEd. 2015;12: 1508-1513. doi:10.1038/nm.3985

The architecture of the SARS-CoV-2 transcriptome. Kim D, et al. Cell. 2020; 181:914-921.e10. doi: 10.1016/j.cell.2020.04.011.

Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Yan R et al. Science. 2020. https://doi.org/10.1126/science.abb2762

Cellular and Molecular Immunobiology. AK Abbas, AH lichtman, S Pillai (Eds). Elsevier 7th Edition 2012.

SARS and MERS: recent insights into emerging coronaviruses. de Wit M et al. Nat.Rev.Microbiol. 2016;14: 523-533.

Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients. Hadjadj J. et al. https://doi.org/10.1101/2020.04.19.20068015

Imbalanced hostresponse to SARS-CoV-2 drives development of COVID-19. Blanco-Melo D. et al. (in press) https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00985.pdf

Dysregulated Type I Interferon and InflammatoryMonocyte-Macrophage Responses Cause LethalPneumonia in SARS-CoV-Infected Mice. Channappanavar R et al. Cell Host & Microbe, 2016;19:181–193 https://www.cell.com/action/showPdf?pii=S1931-3128%2816%2930006-3

New immunodeficiency syndromes that help us understand the IFN-mediated antiviral immune response. Jing H et al. Curr Opin Pediatr. 2019;31:815-820. https://journals.lww.com /co-pediatrics/Abstract/2019/12000/New_immunodeficiency_syndromes_that_help_us.20.aspx

T cell-mediated immune response to respiratory coronaviruses. Channappanavar R et al. Immunol Res 2014 59:118–128. https://link.springer.com/content/pdf/10.1007/s12026-014-8534-z.pdf

Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Grifoni A. et al. Cell https://doi.org/10.1016/j.cell.2020.05.015

Antibody Responses to SARS-CoV-2 in Patients of Novel Coronavirus Disease 2019. Zhao J. et al. Clin Infect Dis. 2020:ciaa344. doi: 10.1093/cid/ciaa344. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa344/5812996

Antibody Detection and Dynamic Characteristics in Patients With COVID-19. Xiang F et al. Clin Infect Dis. 2020;ciaa461. https://academic.oup.com/cid/advance-article/doi/10.1093 /cid/ciaa461/5822173

Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Kai-Wang To et al. Lancet Infect.Dis.2020;5:565-574. https://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930196-1

Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. Wu F et al. https://www.medrxiv.org/content/10.1101/2020.03.30.20047365v2

A serological assay to detect SARS-CoV-2 seroconversion in humans. Amanat F et al. Nat Med. 2020 May 12. doi: 10.1038/s41591-020-0913-5.

Humoral immune response 1 and prolonged PCR positivity in a cohort of 1343 SARS-CoV 2 patients in the New York City region. Wajnberg A et al. medRxiv preprint doi: https://doi.org/10.1101/2020.04.30.20085613

A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. Huang AT et al. https://www.medrxiv.org/content/10.1101/2020.04.14.20065771v1

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals Robbiani DF et al. MedRixV pre-print. doi: https://doi.org/10.1101/2020.05.13.092619

Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Pinto D et al. Cell 2020 https://doi.org/10.1038/s41586-020-2349-y

SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Chandrashekar A et al. Science 2020 https://science.sciencemag.org/content/early/2020/05/19/science.abc4776

Longitudinal profile of antibodies against SARS-coronavirus in SARS patients and their clinical significance. Hongying MO et al. Respirology 2006;49-53.

Persistence of Antibodies against Middle East Respiratory Syndrome Coronavirus. Payne DC et al. Emergon Infectious Dis 2016;22:1824-26.

The Behaviour of Recent Isolates of Human Respiratory Coronavirus In Vitro and in Volunteers: Evidence of Heterogeneity Among 229E-Related Strains. Sylvia E. Reed. J.Med.Virol.1984;13:179-192.

A Strategic Approach to COVID-19 Vaccine R&D. Corey L et al. Science 2020;eabc5312. doi: 10.1126/science.abc5312. Online ahead of print.

A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Yan Wu Y et al. Science 10.1126/science.abc2241 (2020).

The race is on for antibodies that stop the new coronavirus. Cohen J. Science 2020: 368; 6491: 564-565. DOI: 10.1126/science.368.6491.564

Hu W et al. SARS-CoV Regulates Immune Function-Related Gene Expression in Human Monocytic Cells. Viral Immunol. 2012;25:277-88. https://www.liebertpub.com/doi/abs/10.1089/vim.2011.0099?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=vim

Clinical Features of Patients Infected With 2019 Novel Coronavirus in Wuhan, China. Huang C. Lancet 2020;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930183-5

Clinical and immunological features of severe and moderate coronavirus disease 2019. Chen G et al. J Clin Invest. 2020. https://doi.org/10.1172/JCI137244.

Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Zheng M. et al. Cellular & Molecular Immunology 2020;17:533–535. https://www.nature.com/articles/s41423-020-0402-2.pdf?proof=trueIn%25EF%25BB%25BF

Qin C et al. Dysregulation of Immune Response in Patients With COVID-19 in Wuhan, China. Clin Infect Dis. 2020;ciaa248. doi: 10.1093/cid/ciaa248. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa248/ 5803306

TH17 Responses in Cytokine Storm of COVID-19: An Emerging Target of JAK2 Inhibitor Fedratinib. Wu D et al. J Microbiol Immunol Infect. 2020;S1684-1182 doi: 10.1016/j.jmii.2020.03.005. https://www.sciencedirect.com/science/article/pii/S1684118220300657?via%3Dihub

Down-regulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in COVID-19 Patients. Ouyang D. et al. Clin Infect Dis . 2020;ciaa462.doi: 10.1093/cid/ciaa462.

The laboratory tests and host immunity of COVID-19 patients with different severity of illness. Wang F. JCI insight 10.1172/jci.insight.137799 (in press).

Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure Giamarellos-Bourboulis EJ et al. Cell Host & Microbe,2020, (in press) https://www.sciencedirect.com/science/article/pii/S1931312820302365?via%3Dihub

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Tang N et al. J Thromb Haemost. 2020;18:844–847?https://onlinelibrary.wiley.com/doi/epdf/10.1111/jth.14768

Hematological findings and complications of COVID-19. Terpos E et al. Am J Hematol. 2020 doi: 10.1002/ajh.25829. https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.25829

Publicado

30-05-2020

Número

Sección

Aula Magna