Gaytán GCJ, Palacios CA, Sánchez AJS, Franco GJ

Language: Spanish
References: 30
Page: 000
PDF size: 279.34 Kb.

ABSTRACT

Introduction: The pathophysiological principles of pneumonia secondary to SARS-CoV-2 infection have been described, where the cytokine cascade was identified as the main factor for the development of organic lesions. Measurements of inflammatory biochemical markers are currently being carried out in search of their relationship with prognosis and possible complications. In a recent study, an index was made relating interleukin 6 and lymphocyte levels and their association with mortality in patients with severe SARS-CoV-2 pneumonia. The index of immune dysregulation (IL-6/lymphocytes) could allow estimating the patients that evolve towards acute respiratory distress syndrome. Objectives: To establish whether there is a relationship between the levels of the immune dysregulation index and the appearance of acute respiratory distress syndrome in patients with SARS-CoV-2 pneumonia. Material and methods: We conducted a retrolective, observational cohort study, in which patients admitted to the ABC Medical Center with the diagnosis of pneumonia due to SARS-CoV-2 from March to July of 2020 were included, in them, measurements of interleukin 6 and lymphocytes on admission and their progress and development of complications were evaluated. A univariate analysis of the selected factors was carried out; the statistical analysis was elaborated in SPSS v 22.1, frequency measures were examined and the analysis of the risk factors was carried out with the Fisher and χ² tests. Results: 346 patients were analyzed, the immune dysregulation index presented an average of 157 in the group corresponding to ARDS, while in the control group the average was 38. Of the patients with a diagnosis of ARDS, 18.6% died, while in the control group only 0.47%. The ROC curve was used for the analysis of the sensitivity and specificity of the index as a predictor of evolution towards ARDS with a sensitivity finding of 68.2% and a specificity of 77% with a cut-off point of 99. Conclusion: The prediction of complications in the context of SARS-CoV-2 will allow timely measures to be taken. The existence of predictive indices is a useful tool but it requires multiple and validated analyses in different populations to have a high level of safety when making decisions based on them. In this study, the immune dysregulation index has been shown as a possible predictor of evolution towards ARDS; however, the establishment of therapeutic measures should continue in relation to clinical, biochemical and imaging findings.

REFERENCES

1. World Health Organization. Coronavirus disease (COVID-19) outbreak. Available in: https://www.who.int

2. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-574.

3. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-544.

4. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181-192.

5. Peiris JS, Chu CM, Cheng VC, Chan KS, Hung IF, Poon LL, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767-1772.

6. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1953-1966.

7. Van der Hoek L, Pyrc K, Jebbink MF, Vermeulen-Oost W, Berkhout RJ, Wolthers KC, et al. Identification of a new human coronavirus. Nat Med. 2004;10(4):368-373.

8. Ding Y, Wang H, Shen H, Li Z, Geng J, Han H, et al. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol. 2003;200(3):282-289.

9. Nicholls JM, Poon LL, Lee KC, Ng WF, Lai ST, Leung CY, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet. 2003;361(9371):1773-1778.

10. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273.

11. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260-1263.

12. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-422.

13. Perlman S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol. 2005;5(12):917-927.

14. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.

15. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069.

16. Wan S, Yi Q, Fan Sh, Lv J, Zhang X, Guo L, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). MedRxiv. 2020. doi: 10.1101/2020.02.10.20021832 (preprint).

17. Wang C, Xie J, Zhao L, Fei X, Zhang H, Tan Y, et al. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. EBioMedicine. 2020;57:102833.

18. Peiris JS, Guan Y, Yuen KY. Severe acute respiratory syndrome. Nat Med. 2004;10(12 Suppl):S88-S97.

19. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, et al. Cytokine release syndrome. J Immunother Cancer. 2018;6(1):56.

20. Matthys P, Dillen C, Proost P, Heremans H, Van Damme J, Billiau A. Modification of the anti-CD3-induced cytokine release syndrome by anti-interferon-gamma or anti-interleukin-6 antibody treatment: protective effects and biphasic changes in blood cytokine levels. Eur J Immunol. 1993;23(9):2209-2216.

21. Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8(8):959-970.

22. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015;16(5):448-457.

23. Pathan N, Hemingway CA, Alizadeh AA, Stephens AC, Boldrick JC, Oragui EE, et al. Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock. Lancet. 2004;363(9404):203-209.

24. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265(3):621-636.

25. Drosten C, Günther S, Preiser W, van der Werf S, Brodt HR, Becker S, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1967-1976.

26. Kalaria DR, Parker K, Reynolds GK, Laru J. An industrial approach towards solid dosage development for first-in-human studies: Application of predictive science and lean principles. Drug Discov Today. 2020;25(3):505-518.

27. Chen H, Wang J, Su N, Bao X, Li Y, Jin J. Simplified immune-dysregulation index: a novel marker predicts 28-day mortality of intensive care patients with COVID-19. Intensive Care Med. 2020;46(8):1645-1647.

28. Kelsey JL, Whittemore AS, Evans AS. Methods in observational epidemiology. 2nd ed. New York: Oxford University Press; 1996.

29. Fleiss JL. Statistical methods for rates and proportions. New York: Wiley & sons; 1981.

30. Chávez-Iñiguez JS, García-García G, Lombardi R. Epidemiología y desenlaces de la lesión renal aguda en Latinoamérica. Gac Med Mex. 2018;154(Suppl: 1):6-14.