COVID-19: Understanding the cytokine storm

Authors

DOI:

https://doi.org/10.33448/rsd-v10i5.15150

Keywords:

SARS-CoV-2; COVID-19; Cytokine.

Abstract

SARS-CoV-2 spread rapidly across China and soon received worldwide attention, prompting the World Health Organization (WHO) to declare, on January 30, 2020, SARS-CoV-2 infection as a public health emergency of international interest. It is a literature review that aims to update and expand the available information about SARS-CoV-2, covering the immune response against it and the consequent formation of the cytokine storm. In some individuals, the immune system exacerbated response causes hyperstimulation of the defense cells, causing hyperinflammation due to the storm of pro-inflammatory cytokines (TNF-α, IL-1-β, IL-6, IL-12 and chemokines). This hyperinflammation characterizes the pathophysiology of severe COVID-19 that causes pathological changes mainly in the lungs, being a predictor of the disease severity due to its strong association with multiple organ failure, which can lead to death. The measurement of serum levels of IL-6 and IL-10 were considered predictors of severe disease and can be used to diagnose patients with a higher risk of worsening the disease. In conclusion, elevations in serum levels of proinflammatory cytokines are usually present in severe COVID-19. However, further studies are needed to establish differences between patients with COVID-19 who develop a protective and balanced inflammatory reaction from those who develop an exaggerated inflammatory reaction, with a consequent pathological cytokine storm.

References

Abbas, A. K., Lichtman, A. H. Pillai, S. (2021). Cellular and Molecular Immunology (10a ed.). Oxford. Elsevier. 43- 89.

Ali, A., & Vijayan, R. (2020). Dynamics of the ACE2–SARS-CoV-2/SARS-CoV spike protein interface reveal unique mechanisms. Scientific reports, 10(1), 1-12. https://doi.org/10.1038/s41598-020-71188-3

Berhe, B., Legese, H., Degefa, H., Adhanom, G., Gebrewahd, A., Mardu, F., & Negash, H. (2020). Global epidemiology, pathogenesis, immune response, diagnosis, treatment, economic and psychological impact, challenges, and future prevention of COVID-19: A scoping review. MedRxiv. https://doi.org/10.1101/2020.04.02.20051052

Cao, X. (2020). COVID-19: immunopathology and its implications for therapy. Nature reviews immunology, 20(5), 269-270. https://doi.org/10.1038/s41577-020-0308-3

Catanzaro, M., Fagiani, F., Racchi, M., Corsini, E., Govoni, S., & Lanni, C. (2020). Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal transduction and targeted therapy, 5 (1), 1-10. https://doi.org/10.1038/s41392-020-0191-1

Cavalcante, J. R., Cardoso-dos-Santos, A. C., Bremm, J. M., Lobo, A. D. P., Macário, E. M., Oliveira, W. K. D., & França, G. V. A. D. (2020). COVID-19 en Brasil: evolución de la epidemia hasta la semana epidemiológica 20 de 2020. Epidemiologia e Serviços de Saúde, 29(4). https://doi.org/10.5123/s1679-49742020000400010

Cortegiani, A., Ippolito, M., Greco, M., Granone, V., Protti, A., Gregoretti, C., Giarratano, A., Einav, S., & Cecconi, M. (2020). Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review. Pulmonology. https://doi.org/10.1016/j.pulmoe.2020.07.003

Cruz, A. S., Mendes-Frias, A., Oliveira, A. I., Dias, L., Matos, A. R., Carvalho, A., Capela, C., Pedrosa, J., Castro, A. G., & Silvestre, R. (2021). Interleukin-6 is a biomarker for the development of fatal fatal severe acute respiratory syndrome coronavirus 2 pneumonia. Frontiers in immunology, 12, 263. DOI: https://doi.org/10.3389/fimmu.2021.613422

De Biasi, S., Meschiari, M., Gibellini, L., Bellinazzi, C., Borella, R., Fidanza, L., Gozzi, L., Iannone, A., Lo Tartaro, D., Mattioli, M., Paolini, A., Menozzi, M., Milic, J., Franceschi, G., Fantini, R., Tonelli, R., Sita, M., Sarti, M., Trenti, T., & Cossarizza, A. (2020). Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia. Nature communications, 11(1), 1-17. https://doi.org/10.1038/s41467-020-17292-4

De Sordi, L. H. S., Magalhães, I. S. O., Casselhas, D. A., & Andrade, M. C. (2020). The Role of Innate Immunity in COVID-19. Health Sciences Journal, 10(3), 5-8. https://doi.org/10.21876/rcshci.v10i3.997

Dong, X., Tian, Z., Shen, C., & Zhao, C. (2020). An overview of potential therapeutic agents to treat COVID-19. Bioscience trends, 14(5), 318-327. https://doi.org/10.5582/bst.2020.03345

Ellinghaus, D., Degenhardt, F., Bujanda, L., Buti, M., Albillos, A., Invernizzi, P. & Kayhan, S. (2020). Genomewide association study of severe Covid-19 with respiratory failure. New England Journal of Medicine, 383(16), 1522-1534. DOI: https://doi.org/10.1056/NEJMoa2020283

Fajgenbaum, D. C., & June, C. H. (2020). Cytokine storm. New England Journal of Medicine, 383(23), 2255-2273. https://doi.org/10.1056/NEJMra2026131

Frieman, M., Heise, M., & Baric, R. (2008). SARS coronavirus and innate immunity. Virus research, 133 (1), 101-112. https://doi.org/10.1016/j.virusres.2007.03.015

Gorbalenya, A. E., Baker, S. C., Baric, R., Groot, R. J. D., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., Penzar, D., Perlman, S., Poon, L. L. M., Samborskiy, D., Sidorov, I. A., Sola, I., & Ziebuhr, J. (2020). Severe acute respiratory syndrome-related coronavirus: The species and its viruses–a statement of the Coronavirus Study Group. Nature Microbiology. https://doi.org/10.1101/2020.02.07.937862

Guo, Y. R., Cao, Q. D., Hong, Z. S., Tan, Y. Y., Chen, S. D., Jin, H. J., Tan, K. S., Wang, D. Y., & Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Military Medical Research, 7(1), 1-10. https://doi.org/10.1186/s40779-020-00240-0

Han, H., Ma, Q., Li, C., Liu, R., Zhao, L., Wang, W., Zhang, P., Liu, X., Gao, G., Liu, F., Jiang, Y., Cheng, X., Zhu, C., & Xia, Y. (2020). Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerging microbes & infections, 9(1), 1123-1130. https://doi.org/10.1080/22221751.2020.1770129

Hermine, O., Mariette, X., Tharaux, P. L., Resche-Rigon, M., Porcher, R., & Ravaud, P. (2021). Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA internal medicine, 181(1), 32-40. https://doi.org/10.1001/jamainternmed.2020.6820

Hu, B., Guo, H., Zhou, P., & Shi, Z. L. (2020). Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews Microbiology, 1-14. https://doi.org/10.1038/s41579-020-00459-7

Jose, R. J., & Manuel, A. (2020). COVID-19 cytokine storm: the interplay between inflammation and coagulation. The Lancet Respiratory Medicine, 8(6), e46-e47. https://doi.org/10.1016/S2213-2600(20)30216-2

Kumar, S., Nyodu, R., Maurya, V. K., & Saxena, S. K. (2020). Morphology, genome organization, replication, and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Coronavirus Disease 2019 (COVID-19) (pp. 23-31). Springer, Singapore. https://doi.org/10.1007/978-981-15-4814-7_3

Li, G., Fan, Y., Lai, Y., Han, T., Li, Z., Zhou, P., Pan, P., Wang, W., Hu, D., Liu, X., Zhang, Q., & Wu, J. (2020). Coronavirus infections and immune responses. Journal of medical virology, 92(4), 424-432. https://doi.org/10.1002/jmv.25685

Liang, X. (2020). Is COVID-19 more severe in older men? Postgraduate medical journal, 96(1137), 426-426. http://dx.doi.org/10.1136/postgradmedj-2020-137867

Lin, L., Lu, L., Cao, W., & Li, T. (2020). Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia. Emerging microbes & infections, 9(1), 727-732. https://doi.org/10.1080/22221751.2020.1746199

Long, Q. X., Tang, X. J., Shi, Q. L., Li, Q., Deng, H. J., Yuan, J., Hu, J. L., Xu, W., Zhang, Y., Lv, F. J., Su, K., Zhang, F., Gong, J., Wu, B., Liu, X. M., Li, J. J., Qiu, J. F., Chen, J., & Huang, A. L. (2020). Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nature medicine, 26(8), 1200-1204. https://doi.org/10.1038/s41591-020-0965-6

Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L. & Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The lancet, 395(10224), 565-574. https://doi.org/10.1016/S0140-6736(20)30251-8

Marinho, D. S. (2021). Hiperfibrinólise perioperatória—fisiologia e fisiopatologia. Brazilian Journal of Anesthesiology, 71(65), 65-75. https://doi.org/10.1016/j.bjane.2020.12.007

Ministério da Saúde. (2021). COVID-19 no Brasil. Banco de dados do Sistema Único de Saúde-DATASUS. https://susanalitico.saude.gov.br/extensions/covid-19_html/covid-19_html.html

Mirtaleb, M. S., Mirtaleb, A. H., Nosrati, H., Heshmatnia, J., Falak, R., & Emameh, R. Z. (2021). Potential therapeutic agents to COVID-19: An update review on antiviral therapy, immunotherapy, and cell therapy. Biomedicine & Pharmacotherapy, 111518. https://doi.org/10.1016/j.biopha.2021.111518

Molaei, S., Dadkhah, M., Asghariazar, V., Karami, C., & Safarzadeh, E. (2021). The immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2: Vaccine design strategies. International immunopharmacology, 107051. https://doi.org/10.1016/j.intimp.2020.107051

Munjal, M., Das, S., Chatterjee, N., Setra, A. E., & Govil, D. (2020). Systemic Involvement of Novel Coronavirus (COVID-19): A Review of Literature. Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine, 24(7), 565. https://doi.org/10.5005/jp-journals-10071-23498

Nile, S. H., Nile, A., Qiu, J., Li, L., Jia, X., & Kai, G. (2020). COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine & growth factor reviews, 53, 66-70. https://doi.org/10.1016/j.cytogfr.2020.05.002

Ong, E. Z., Chan, Y. F. Z., Leong, W. Y., Lee, N. M. Y., Kalimuddin, S., Mohideen, S. M. H., Chan, K. S., Tan, A. T., Bertoletti, A., Ooi, E. E., & Low, J. G. H. (2020). A dynamic immune response shapes COVID-19 progression. Cell host & microbe, 27(6), 879-882. https://doi.org/10.1016/j.chom.2020.03.021

Overbaugh, J. (2020). Understanding protection from SARS-CoV-2 by studying reinfection. Nature Medicine, 26(11), 1680-1681. https://doi.org/10.1038/s41591-020-1121-z

Potì, F., Pozzoli, C., Adami, M., Poli, E., & Costa, L. G. (2020). Treatments for COVID-19: emerging drugs against the coronavirus. Acta Bio Medica: Atenei Parmensis, 91(2), 118. https://doi.org/10.23750/abm.v91i2.9639

Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., Xie, C., Ma, K., Shang, K., Wang, W., & Tian, D. S. (2020). Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clinical infectious diseases, 71(15), 762-768. https://doi.org/10.1093/cid/ciaa248

Rabi, F. A., Al Zoubi, M. S., Kasasbeh, G. A., Salameh, D. M., & Al-Nasser, A. D. (2020). SARS-CoV-2 and coronavirus disease 2019: what we know so far. Pathogens, 9(3), 231. https://doi.org/10.3390/pathogens9030231

Ragab, D., Salah Eldin, H., Taeimah, M., Khattab, R., & Salem, R. (2020). The COVID-19 cytokine storm; what we know so far. Frontiers in immunology, 11, 1446. https://doi.org/10.3389/fimmu.2020.01446

Rothan, H. A., & Byrareddy, S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of autoimmunity, 109, 102433. https://doi.org/10.1016/j.jaut.2020.102433

Shereen, M. A., Khan, S., Kazmi, A., Bashir, N., & Siddique, R. (2020, July). COVID-19 infection: Emergence, transmission, and characteristics of human coronaviruses. Journal of Advanced Research, 24(2020), 91–98. https://doi.org/10.1016/j.jare.2020.03.005

Soy, M., Keser, G., Atagündüz, P., Tabak, F., Atagündüz, I., & Kayhan, S. (2020). Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clinical rheumatology, 39, 2085-2094. https://doi.org/10.1007/s10067-020-05190-5

Subbarao, K., & Mahanty, S. (2020). Respiratory virus infections: understanding COVID-19. Immunity, 52(6), 905-909. https://doi.org/10.1016/j.immuni.2020.05.004

Tavares, C. D. A. M., Avelino-Silva, T. J., Benard, G., Cardozo, F. A. M., Fernandes, J. R., Girardi, A. C. C., & Jacob Filho, W. (2020). Alterações da ECA2 e Fatores de Risco para Gravidade da COVID-19 em Pacientes com Idade Avançada. Arquivos Brasileiros de Cardiologia, 115(4), 701-707. https://doi.org/10.36660/abc.20200487

To, K. K. W., Hung, I. F. N., Ip, J. D., Chu, A. W. H., Chan, W. M., Tam, A. R., & Yuen, K. Y. (2020). Coronavirus disease 2019 (COVID-19) re-infection by a phylogenetically distinct severe acute respiratory syndrome coronavirus 2 strain confirmed by whole genome sequencing. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaa1275

Veras, F. P., Pontelli, M. C., Silva, C. M., Toller-Kawahisa, J. E., de Lima, M., Nascimento, D. C., Schneider, A. H., Caetite, D., Tavares, L. A., Paiva, I. M., Rosales, R., Colon, D., Martins, R., Castro, I. A., Almeida, G. M., Lopes, M. I. F., Benatti, M. N., Bonjorno, L. P., Giannini, M. G. & Cunha, F. Q. (2020). SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology. Journal of Experimental Medicine, 217(12). https://doi.org/10.1084/jem.20201129

World Health Organization. (2021). WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int

Zhang, W., Zhang, C., Bi, Y., Yuan, L., Jiang, Y., Hasi, C., & Kong, X. (2021). Analysis of COVID-19 epidemic and clinical risk factors of patients under epidemiological Markov model. Results in Physics, 22, 103881. https://doi.org/10.1016/j.rinp.2021.103881

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. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet, 395(10229), 1054-1062. https://doi.org/10.1016/S0140-6736(20)30566-3

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12/05/2021

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NAPOLEÃO, R. N. M. .; SANTIAGO, A. B. G. .; MOREIRA, M. A. .; SILVA, S. L. da; SILVA , S. F. R. da . COVID-19: Understanding the cytokine storm . Research, Society and Development, [S. l.], v. 10, n. 5, p. e43710515150, 2021. DOI: 10.33448/rsd-v10i5.15150. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/15150. Acesso em: 26 nov. 2024.

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Vol. 10 No. 5

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