Inmunosupresión vs. Inmunorregulación en COVID-19

Palabras clave: COVID-19, inmunosupresión, inmunorregulación, Tocilizumab, Colchicina, Baricitinib, inflamación

Resumen

La COVID-19 tiene un espectro clínico variable, desde una infección asintomática hasta una enfermedad crítica con desenlace mortal. Se han propuesto múltiples terapias, algunas con efectos a nivel de la respuesta inmunológica. En este estudio evaluamos el uso de Tocilizumab, Colchicina y Baricitinib en pacientes hospitalizados con infección por SARS-CoV-2. Se examinaron los expedientes clínicos de 133 pacientes hospitalizados con COVID-19 en 3 hospitales. Inicialmente, ninguno de estos medicamentos mostró ser superior al grupo Control en disminuir la mortalidad. Sin embargo, se realizó un análisis estratificado evidenciando que Tocilizumab puede reducir la mortalidad hasta un 3.7% vs 28.12% (p=0.01). La estancia intrahospitalaria fue mayor en los pacientes que recibieron Baricitinib y Tocilizumab comparados con el Control (14.25±2.06 y 10.58±3.66 respectivamente vs 8.30±2.86). Finalmente, Tocilizumab fue el único fármaco que redujo la probabilidad de un aumento en el requerimiento de oxígeno suplementario (OR 0.3094, 0.95% IC [0.1031-0.9287]). La terapia inmunorreguladora muestra ser útil para el manejo de pacientes con COVID-19.

Descargas

La descarga de datos todavía no está disponible.

Citas

Able, B. C., (1945). Nombre del artículo. Nombre de la revista 35, 123–126. DOI: 10.3923/ijbc.2010.190.202

Al-Salama, Z. T., & Scott, L. J. (2018). Baricitinib: A Review in Rheumatoid Arthritis. Drugs, 78(7), 761-772. https://doi.org/10.1007/s40265-018-0908-4

Atzeni, F., Masala, I. F., Rodríguez-Carrio, J., Ríos-Garcés, R., Gerratana, E., La Corte, L., . . . Cervera, R. (2021). The Rheumatology Drugs for COVID-19 Management: Which and When? J Clin Med, 10(4). https://doi.org/10.3390/jcm10040783

Bronte, V., Ugel, S., Tinazzi, E., Vella, A., De Sanctis, F., Canè, S., . . . Olivieri, O. (2020). Baricitinib restrains the immune dysregulation in patients with severe COVID-19. J Clin Invest, 130(12), 6409-6416. https://doi.org/10.1172/jci141772

Burkard, C., Verheije, M. H., Wicht, O., van Kasteren, S. I., van Kuppeveld, F. J., Haagmans, B. L., . . . de Haan, C. A. (2014). Coronavirus cell entry occurs through the endo-/lysosomal pathway in a proteolysis-dependent manner. PLoS Pathog, 10(11), e1004502. https://doi.org/10.1371/journal.ppat.1004502

Campochiaro, C., Della-Torre, E., Cavalli, G., De Luca, G., Ripa, M., Boffini, N., . . . Group, T.-R. S. (2020). Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study. Eur J Intern Med, 76, 43-49. https://doi.org/10.1016/j.ejim.2020.05.021

Cantini, F., Niccoli, L., Matarrese, D., Nicastri, E., Stobbione, P., & Goletti, D. (2020). Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact. The Journal of infection, 81(2), 318-356. https://doi.org/10.1016/j.jinf.2020.04.017

Capra, R., De Rossi, N., Mattioli, F., Romanelli, G., Scarpazza, C., Sormani, M. P., & Cossi, S. (2020). Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med, 76, 31-35. https://doi.org/10.1016/j.ejim.2020.05.009

Chen, L. Y. C., Hoiland, R. L., Stukas, S., Wellington, C. L., & Sekhon, M. S. (2021). Assessing the importance of interleukin-6 in COVID-19. The Lancet Respiratory Medicine, 9(2), e13. https://doi.org/10.1016/S2213-2600(20)30600-7

Colaneri, M., Bogliolo, L., Valsecchi, P., Sacchi, P., Zuccaro, V., Brandolino, F., . . . The Covid Irccs San Matteo Pavia Task, F. (2020). Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE). Microorganisms, 8(5). https://doi.org/10.3390/microorganisms8050695

Consult, R. C. C. (2020). CALL score. RCCC. https://www.rccc.eu/COVID/CALL.html

Deftereos, S. G., Giannopoulos, G., Vrachatis, D. A., Siasos, G. D., Giotaki, S. G., Gargalianos, P., . . . Stefanadis, C. (2020). Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open, 3(6), e2013136. https://doi.org/10.1001/jamanetworkopen.2020.13136

DGE. (2021, Jun 19th, 2021). Covid-19 México. Retrieved Jun 20th, 2021 from https://datos.covid-19.conacyt.mx/

Diao, B., Wang, C., Tan, Y., Chen, X., Liu, Y., Ning, L., . . . Chen, Y. (2020). Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol, 11, 827. https://doi.org/10.3389/fimmu.2020.00827

Dos Santos, W. G. (2020). Natural history of COVID-19 and current knowledge on treatment therapeutic options. Biomed Pharmacother, 129, 110493. https://doi.org/10.1016/j.biopha.2020.110493

Durán-Méndez, A., Aguilar-Arroyo, A. D., Vivanco-Gómez, E., Nieto-Ortega, E., Pérez-Ortega, D., Jiménez-Pérez, C., . . . Peón, A. N. (2021). Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study. Scientific Reports, 11(1), 19728. https://doi.org/10.1038/s41598-021-99291-z

Frediansyah, A., Nainu, F., Dhama, K., Mudatsir, M., & Harapan, H. (2021). Remdesivir and its antiviral activity against COVID-19: A systematic review. Clin Epidemiol Glob Health, 9, 123-127. https://doi.org/10.1016/j.cegh.2020.07.011

Gokhale, Y., Mehta, R., Karnik, N., Kulkarni, U., & Gokhale, S. (2020). Tocilizumab improves survival in patients with persistent hypoxia in severe COVID-19 pneumonia. EClinicalMedicine, 24, 100467. https://doi.org/10.1016/j.eclinm.2020.100467

Guaraldi, G., Meschiari, M., Cozzi-Lepri, A., Milic, J., Tonelli, R., Menozzi, M., . . . Mussini, C. (2020). Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol, 2(8), e474-e484. https://doi.org/10.1016/s2665-9913(20)30173-9

Gubernatorova, E. O., Gorshkova, E. A., Polinova, A. I., & Drutskaya, M. S. (2020). IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev, 53, 13-24. https://doi.org/10.1016/j.cytogfr.2020.05.009

Ji, D., Zhang, D., Xu, J., Chen, Z., Yang, T., Zhao, P., . . . Qin, E. (2020). Prediction for Progression Risk in Patients With COVID-19 Pneumonia: The CALL Score. Clin Infect Dis, 71(6), 1393-1399. https://doi.org/10.1093/cid/ciaa414

Kalil, A. C., Patterson, T. F., Mehta, A. K., Tomashek, K. M., Wolfe, C. R., Ghazaryan, V., . . . Beigel, J. H. (2021). Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med, 384(9), 795-807. https://doi.org/10.1056/NEJMoa2031994

Karatza, E., Ismailos, G., & Karalis, V. (2021). Colchicine for the treatment of COVID-19 patients: efficacy, safety, and model informed dosage regimens. Xenobiotica, 51(6), 643-656. https://doi.org/10.1080/00498254.2021.1909782

Klopfenstein, T., Zayet, S., Lohse, A., Balblanc, J. C., Badie, J., Royer, P. Y., . . . Conrozier, T. (2020). Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Med Mal Infect, 50(5), 397-400. https://doi.org/10.1016/j.medmal.2020.05.001

Luo, W., Li, Y. X., Jiang, L. J., Chen, Q., Wang, T., & Ye, D. W. (2020). Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19. Trends Pharmacol Sci, 41(8), 531-543. https://doi.org/10.1016/j.tips.2020.06.007

Madrid-García, A., Pérez, I., Colomer, J. I., León-Mateos, L., Jover, J. A., Fernández-Gutiérrez, B., . . . Rodríguez-Rodríguez, L. (2021). Influence of colchicine prescription in COVID-19-related hospital admissions: a survival analysis. Ther Adv Musculoskelet Dis, 13, 1759720x211002684. https://doi.org/10.1177/1759720x211002684

Manenti, L., Maggiore, U., Fiaccadori, E., Meschi, T., Antoni, A. D., Nouvenne, A., . . . Peruzzi, L. (2021). Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study. PLoS One, 16(3), e0248276. https://doi.org/10.1371/journal.pone.0248276

Nawangsih, E. N., Kusmala, Y. Y., Rakhmat, II, Handayani, D. R., Juliastuti, H., Wibowo, A., . . . Pranata, R. (2021). Colchicine and mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia: A systematic review, meta-analysis, and meta-regression. Int Immunopharmacol, 96, 107723. https://doi.org/10.1016/j.intimp.2021.107723

Prompetchara, E., Ketloy, C., & Palaga, T. (2020). Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol, 38(1), 1-9. https://doi.org/10.12932/ap-200220-0772

Richardson, P., Griffin, I., Tucker, C., Smith, D., Oechsle, O., Phelan, A., . . . Stebbing, J. (2020). Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. The Lancet, 395(10223), e30-e31. https://doi.org/https://doi.org/10.1016/S0140-6736(20)30304-4

Rojas-Marte, G., Khalid, M., Mukhtar, O., Hashmi, A. T., Waheed, M. A., Ehrlich, S., . . . Shani, J. (2020). Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study. QJM, 113(8), 546-550. https://doi.org/10.1093/qjmed/hcaa206

Rosas, I. O., Bräu, N., Waters, M., Go, R., Hunter, B. D., Bhagani, S., . . . Malhotra, A. (2020). Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia. medRxiv, 2020.2008.2027.20183442. https://doi.org/10.1101/2020.08.27.20183442

Sevilla-Castillo, F., Roque-Reyes, O. J., Romero-Lechuga, F., Gómez-Núñez, M. F., Castillo-López, M., Medina-Santos, D., . . . Peón, A. N. (2021). Both Chloroquine and Lopinavir/Ritonavir Are Ineffective for COVID-19 Treatment and Combined Worsen the Pathology: A Single-Center Experience with Severely Ill Patients. Biomed Res Int, 2021, 8821318. https://doi.org/10.1155/2021/8821318

Siddiqi, H. K., & Mehra, M. R. (2020). COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant, 39(5), 405-407. https://doi.org/10.1016/j.healun.2020.03.012

Somers, E. C., Eschenauer, G. A., Troost, J. P., Golob, J. L., Gandhi, T. N., Wang, L., . . . Pogue, J. M. (2020). Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis. https://doi.org/10.1093/cid/ciaa954

Tardif, J. C., Bouabdallaoui, N., L'Allier, P. L., Gaudet, D., Shah, B., Pillinger, M. H., . . . Boivin, G. (2021). Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med. https://doi.org/10.1016/s2213-2600(21)00222-8

Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. F. P. (2020). The trinity of COVID-19: immunity, inflammation and intervention. Nature reviews. Immunology, 20(6), 363-374. https://doi.org/10.1038/s41577-020-0311-8

The, R.-C. A. P. I., Gordon, A. C., Mouncey, P. R., Al-Beidh, F., Rowan, K. M., Nichol, A. D., . . . Derde, L. P. G. (2021). Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19 – Preliminary report. medRxiv, 2021.2001.2007.21249390. https://doi.org/10.1101/2021.01.07.21249390

WHO. (2021, June 19th). WHO Coronavirus (COVID-19) Dashboard. Retrieved June 20th, 2021 from https://covid19.who.int/

Wu, F., Zhao, S., Yu, B., Chen, Y.-M., Wang, W., Song, Z.-G., . . . Zhang, Y.-Z. (2020). A new coronavirus associated with human respiratory disease in China. Nature, 579(7798), 265-269. https://doi.org/10.1038/s41586-020-2008-3

Xu, X., Han, M., Li, T., Sun, W., Wang, D., Fu, B., . . . Wei, H. (2020). Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A, 117(20), 10970-10975. https://doi.org/10.1073/pnas.2005615117

Publicado
2022-01-05
Cómo citar
Durán-Méndez, A., Nieto-Ortega, E., & Peón, A. N. (2022). Inmunosupresión vs. Inmunorregulación en COVID-19. Pädi Boletín Científico De Ciencias Básicas E Ingenierías Del ICBI, 9(18), 146-152. https://doi.org/10.29057/icbi.v9i18.8159