Cytokine storm scale as a prognostic tool of course of viral pneumonia in COVID-19


DOI: https://dx.doi.org/10.18565/therapy.2021.6.42-50

Tkachenko O.Yu., Pervakova M.Yu., Lapin S.V., Masing A.V., Moshnikova A.N., Kuznetsova D.A., Kholopova I.V., Blinova T.V., Surkova E.A., Polushin Yu.S., Afanasiev A.A., Shlyk I.V., Gavrilova E.G., Kornilova E.A., Ivannikova D.A., Trophimov E.A., Mazurov V.I.

1) I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia; 2) I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia, Saint Petersburg
Abstract. The aim of the study is to validate the cytokine storm scale (CSS) in a cohort of patients with COVID-19-associated pneumonia to confirm its diagnostic and informative value.
Material and methods. The study included 48 patients with COVID-19-associated pneumonia who were admitted to hospital for treatment, and 73 intensive care unit (ICU) patients. The levels of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), interleukin 10 (IL-10) and procalcitonin (PCT) were measured using enzyme immunoassay, and CSS was calculated. For each biomarker, grade marks were calculated in the range from 1 to 3: at the border concentration of the studied index, 1 grade mark was awarded, with an average – 2, with a high – 3 (normal values were corresponded to 0 marks). A CSS score of more than 6 was associated with a high risk of adverse COVID-19 outcome.
Results. When assessing the informativeness of CSS indexes concerning mortality prediction, it was found that it had high sensitivity (78,79%; 95% CI: 0,61–0,91) and specificity (81,12%; 95% CI: 71,24–88,80). Also CSS positively and statistically significantly correlated with the NEWS2 scale (0,58; 95% CI: 0,35–0,75), degree of pulmonary damage according to computer tomography data (0,46; 95% CI: 0,20–0,67 ) and the percentage of pulmonary tissue damage (0,38; 95% CI: 0,01–0,61).
Conclusion. The developed CSS has a sufficiently high predictive information value in relation to the risk of an unfavorable prognosis of COVID-19 clinical course. The combined prognostic capabilities of the cytokines IL-6, IL-18, IL-10 and PCT, integrated into a single index, make it more likely to identify patients of high risk of death in case of COVID-19-associated pneumonia.

Literature



  1. Hu B., Guo H., Zhou P. et al. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021; 19(3): 141–54. doi: 10.1038/s41579-020-00459-7.

  2. Guan W., Ni Z., Hu Y. et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382(18): 1708–20. doi: 10.1056/NEJMoa2002032.

  3. Zhou F., Yu T., Du R. 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(10229): 1054–62. doi: 10.1016/S0140-6736(20)30566-3.

  4. Tay M.Z., Poh C.M., Renia L. et al. The trinity of COVID-19: Immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20(6): 363–74. doi: 10.1038/s41577-020-0311-8.

  5. Li C., Zhao C., Bao J. et al. Laboratory diagnosis of coronavirus disease-2019 (COVID-19). Clin Chim Acta. 2020; 510: 35–46. doi: 10.1016/j.cca.2020.06.045.

  6. Han H., Ma Q., Li C. et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020; 9(1): 1123–30. doi: 10.1080/22221751.2020.1770129.

  7. Fan G., Tu C., Zhou F. et al. Comparison of severity scores for COVID-19 patients with pneumonia: A retrospective study. Eur Respir J. 2020; 56(3): 2002113. doi: 10.1183/13993003.02113-2020.

  8. Ткаченко О.Ю., Первакова М.Ю., Лапин С.В. с соавт. Прогностическая роль исследования цитокинов при COVID-19-ассоциированной пневмонии. Вестник Северо-Западного государственного университета им. И.И. Мечникова. 2021; 1: 59–69. [Tkachenko O.Y., Pervakova M.Y., Lapin S V. et al. Prognostic value of cytokines in COVID-19 associated pneumonia. Vestnik Severo-Zapadnogo gosudarstvennogo universiteta im. I.I. Mechnikova = Bulletin of the Northwestern State University named after I.I. Mechnikov. 2021; 1: 59–69 (In Russ.)]. doi: https://dx.doi.org/10.17816/mechnikov61610.

  9. Satıs H., Ozger H.S., Aysert Yıldız P. et al. Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19. Cytokine. 2021; 137: 155302. doi: 10.1016/j.cyto.2020.155302.

  10. Crayne C.B., Albeituni S., Nichols K.E. et al. The immunology of macrophage activation syndrome. Front Immunol. 2019; 10: 119. doi: 10.3389/fimmu.2019.00119.

  11. Qin C., Zhou L., Hu Z. et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020; 71(15): 762–68. doi: 10.1093/cid/ciaa248.

  12. Jamilloux Y., Henry T., Belot A. et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev. 2020; 19(7): 102567. doi: 10.1016/j.autrev.2020.102567.

  13. Coomes E.A., Haghbayan H. Interleukin6 in COVID-19: A systematic review and meta-analysis. Rev Med Virol. 2020; 30(6): 1–9. doi: 10.1002/rmv.2141.

  14. Lauw F.N., Pajkrt D., Hack C.E. et al. Proinflammatory effects of IL-10 during human endotoxemia. J Immunol. 2000; 165(5): 2783–89. doi: 10.4049/jimmunol.165.5.278.

  15. Lu L., Zhang H., Dauphars D.J. et al. A potential role of interleukin 10 in COVID-19 pathogenesis. Trends Immunol. 2021; 42(1): 3–5. doi: 10.1016/j.it.2020.10.012.

  16. Lippi G., Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chim Acta. 2020; 505: 190–91. doi: 10.1016/j.cca.2020.03.004.

  17. Song J., Park D.W, Moon S. et al. Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: a prospective controlled study according to the Sepsis-3 definitions. BMC Infect Dis. 2019; 19(1): 968. doi: 10.1186/s12879-019-4618-7.

  18. Hu R., Han C., Pei S. et al. Procalcitonin levels in COVID-19 patients. Int J Antimicrob Agents. 2020; 56(2): 106051. doi: 10.1016/j.ijantimicag.2020.106051.

  19. Vanska M., Koivula I., Jantunen E. et al. IL-10 combined with procalcitonin improves early prediction of complications of febrile neutropenia in hematological patients. Cytokine. 2012; 60(3): 787–92. doi: 10.1016/j.cyto.2012.07.023.

  20. Liang W., Liang H., Ou L. et al. Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. JAMA Intern Med. 2020; 180(8): 1081–89. doi: 10.1001/jamainternmed.2020.2033.


About the Autors


Olga Yu. Tkachenko, PhD, doctor of clinical laboratory diagnostics of the Laboratory of clinical diagnostic, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: tkachenie@mail.ru. ORCID: 0000-0002-1479-6551. еLibrary SPIN: 6593-8770
Margarita Yu. Pervakova, PhD, doctor of clinical laboratory diagnostics of the Laboratory of clinical diagnostic, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: margaritalerner@gmail.com. ORCID: 0000-0001-9630-257X. еLibrary SPIN: 8820-5850
Sergey V. Lapin, PhD, head of the Laboratory for diagnostics of autoimmune diseases, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: svlapin@mail.ru. ORCID: 0000-0002-4998-3699. еLibrary SPIN: 9852-7501
Alexandra V. Mazing, PhD, leading researcher of the Laboratory of molecular diagnostics, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: alex_mazing@mail.ru. ORCID: 0000-0002-3055-6507. еLibrary SPIN: 4458-4633
Anna N. Moshnikova, doctor of clinical laboratory diagnostics of the Laboratory of clinical diagnostic, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: moshnikova-anna@mail.ru. ORCID: /0000-0002-4604-0660. еLibrary SPIN: 7252-3525
Daria A. Kuznetsova, PhD, doctor of clinical laboratory diagnostics of the Laboratory of clinical diagnostic, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: lariwar@mail.ru. ORCID: 0000-0001-5318-354X. еLibrary SPIN: 6110-6168
Irina V. Kholopova, doctor of clinical laboratory diagnostics of the Laboratory of clinical diagnostic, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: irinakholopova@yandex.ru. ORCID: 0000-0001-9520-453X. еLibrary SPIN: 8964-4523
Elena A.Surkova, candidate of biological sciences, leading researcher of the Laboratory for diagnostics of autoimmune diseases, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: easurkova@mail.ru. ORCID: 0000-0001-5191-0221. еLibrary SPIN: 6518-8128
Tatiana V. Blinova, candidate of biological sciences, leading researcher of the Laboratory for diagnostics of autoimmune diseases, Center for Molecular Medicine of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 994-53-24, +7 (812) 338-71-94. E-mail: tvblinova@list.ru. ORCID: 0000-0003-4896-3319. еLibrary SPIN: 1637-4357
Yuri S. Polushin, MD, professor, academician of RAS, vice-rector for science, head of the Department of anesthesiology and reanimatology, head of the Scientific and Clinical Center for Anesthesiology and Reanimatology of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (812) 338-71-66. E-mail: polushinyus@1spbgmu.ru
Alexey A. Afanasiev, PhD, assistant of the Department of anesthesiology and reanimatology, head of the Department of reanimation and intensive care of the Scientific and Clinical Center of Anesthesiology and Reanimatology of I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. E-mail: alex-txf@mail.ru. ORCID0000-0003-0277-3456; еLibrary SPIN: 4389-6271
Elena G. Gavrilova, PhD, associate professor of the Department of anesthesiology and reanimatology, head of Intensive care unit No. 2, I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. E-mail: egavrilova70@mail.ru. Тел.: 8 (911) 224-01-81. ORCID: 0000-0002-9126-3206
Irina V. Shlyk, MD, professor of the Department of anesthesiology and reanimatology, deputy chief physician of the Clinic for Anesthesiology and Intensive Care, I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russia. Address: 197022, Saint Petersburg, 6/8 Lva Tolstogo Str. Tel.: +7 (911) 837-19-75. E-mail: irina_shlyk@mail.ru. ORCID: 0000-0003-0977-8081. еLibrary SPIN: 1715-1770
Elizaveta A. Kornilova, resident of the Department of therapy, rheumatology, examination of temporary disability and the quality of medical care named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia. Address: 191015, Saint Petersburg, 41 Kirochnaya Str. Tel.: +7 (981) 761-74-18. E-mail: liza_kornilova@bk.ru. ORCID: 0000-0003-0805-6124
Daria A. Ivannikova, resident of the Department of therapy, rheumatology, examination of temporary disability and the quality of medical care named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia. Address: 191015, Saint Petersburg, 41 Kirochnaya Str. Tel.: +7 (930) 128-38-82. E-mail: d.ivannikova@yandex.ru. ORCID: 0000-0002-3321-7586
Evgeny A. Trofimov, MD, associate professor of the Department of therapy, rheumatology, examination of temporary disability and the quality of medical care named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia. Address: 191015, Saint Petersburg, 41 Kirochnaya Str. Tel.: +7 (921) 978-86-26. E-mail: Evgeniy.trofimov@szgmu.ru. ORCID: 0000-0003-3236-4485
Vadim I. Mazurov, MD, professor, academician of RAS, head of the Department of therapy, rheumatology, examination of temporary disability and the quality of medical care named after E.E. Eichwald, I.I. Mechnikov North-Western State Medical University of the Ministry of Healthcare of Russia, Honored Scientist of the Russian Federation. Address: 191015, Saint Petersburg, 41 Kirochnaya Str. Tel.: +7 (921) 951-71-88. E-mail: maz.nwgmu@yandex.ru. ORCID: 0000-0001-8367-3144


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