Prognostic value of cytokines in COVID-19 associated pneumonia

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Abstract

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often complicated by cytokine storm syndrome. Although many interleukins (IL) have predictive value, the sensitivity and specificity of a single marker is limited.

AIM: The purpose of the study is to develop an objective and informative cytokine storm scale for assessing the risk of developing a critical course in patients with COVID-19 associated pneumonia.

MATERIALS AND METHODS: A total of 226 cases of COVID-19 were investigated, 36 (16 %) of which were with poor outcomes. The cytokines IL-1b, IL-2, IL-6, IL-8, IL-10, IL-18, TNF-á, IFNá, IFN-ã were studied by enzyme immunoassay, commercial kits manufactured by Vector-Best, RF.

RESULTS: Since IL-6, IL-10, IL-18, and procalcitonin were associated with disease severity and death, these indicators were integrated into a 12-point scale called the cytokine storm scale. The patients who scored more than 6 points had a high risk of a poor outcome of the disease. According to ROC analysis, the area under the curve for the cytokine storm scale was larger than for each of the four markers separately [AUC 0.90 (95% CI 0.8455–0.9592), p < 0.001].

CONCLUSIONS: Thus, the cytokine storm scale system presents superior performance in determining patients with favorable and fatal outcomes to each individual cytokine.

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About the authors

Olga Yu. Tkachenko

First Pavlov State Medical University

Author for correspondence.
Email: tkachenie@mail.ru
ORCID iD: 0000-0002-1479-6551
SPIN-code: 6593-8770

MD, Cand. Sci. (Med.)

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Margarita Yu. Pervakova

First Pavlov State Medical University

Email: margaritalerner@gmail.com
ORCID iD: 0000-0001-9630-257X
SPIN-code: 8820-5850

MD

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Sergey V. Lapin

First Pavlov State Medical University

Email: svlapin@mail.ru
ORCID iD: 0000-0002-4998-3699
SPIN-code: 9852-7501

MD, Cand. Sci. (Med.)

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Aleksandra V. Mazing

First Pavlov State Medical University

Email: alex_mazing@mail.ru
ORCID iD: 0000-0002-3055-6507
SPIN-code: 4458-4633

MD, Cand. Sci. (Med.), Leading Research Associate

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Darya A. Kuznetsova

First Pavlov State Medical University

Email: lariwar@mail.ru
ORCID iD: 0000-0001-5318-354X
SPIN-code: 6110-6168

MD, Cand. Sci. (Med.)

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Anna N. Moshnikova

First Pavlov State Medical University

Email: moshnikova-anna@mail.ru
ORCID iD: 0000-0002-4604-0660
SPIN-code: 7252-3525

MD

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Irina V. Kholopova

First Pavlov State Medical University

Email: irinakholopova@yandex.ru
ORCID iD: 0000-0001-9520-453X
SPIN-code: 8964-4523

MD

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Tatyana V. Blinova

First Pavlov State Medical University

Email: tvblinova@list.ru
ORCID iD: 0000-0003-4896-3319
SPIN-code: 1637-4357

MD, Cand. Sci. (Med.), Research Associate

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Elena A. Surkova

First Pavlov State Medical University

Email: easurkova@mail.ru
ORCID iD: 0000-0001-5191-0221
SPIN-code: 6518-8128

MD, Cand. Sci. (Med.), Research Associate

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Aleksandr N. Kulikov

First Pavlov State Medical University

Email: ankulikov2005@yandex.ru
ORCID iD: 0000-0002-4544-2967
SPIN-code: 3851-6072

MD, Dr. Sci. (Med.), Professor

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Evgeniy A. Vorobyev

First Pavlov State Medical University

Email: vorobyeveval@gmail.com
ORCID iD: 0000-0001-5891-8621

MD

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Snezhana V. Vorobyeva

First Pavlov State Medical University

Email: blaze04@mail.ru
ORCID iD: 0000-0001-5659-4731

MD

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Oksana V. Stanevich

First Pavlov State Medical University

Email: oksana.stanevich@gmail.com
ORCID iD: 0000-0002-6894-6121
SPIN-code: 9542-2524

MD

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Yuriy S. Polushin

First Pavlov State Medical University

Email: polushinyus@1spbgmu.ru
ORCID iD: 0000-0002-6313-5856
SPIN-code: 2006-1194

MD, Dr. Sci. (Med.), Professor, Academician of the RAS

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Irina V. Shlyk

First Pavlov State Medical University

Email: irina_shlyk@mail.ru
ORCID iD: 0000-0003-0977-8081
SPIN-code: 1715-1770

MD, Dr. Sci. (Med.), Professor

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Alexey Afanasyev

First Pavlov State Medical University

Email: alex-txf@mail.ru
ORCID iD: 0000-0003-0277-3456
SPIN-code: 4389-6271

MD, Cand. Sci. (Med.), Assistant Lecturer

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Elena G. Gavrilova

First Pavlov State Medical University

Email: egavrilova70@mail.ru
ORCID iD: 0000-0002-9126-3206

MD, Cand. Sci. (Med.), Assistant Professor

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Olga N. Titova

First Pavlov State Medical University

Email: titovaon@spb-gmu.ru
ORCID iD: 0000-0003-4678-3904
SPIN-code: 4801-4985

MD, Dr. Sci. (Med.), Professor

Russian Federation, 6-8 L’va Tolstogo str., Saint Petersburg, 197022

Elizaveta V. Volchkova

City Multiprofil Hospital No. 2

Email: elizavetavolch@mail.ru
ORCID iD: 0000-0001-6712-5121

MD

Russian Federation, Saint Petersburg

Vsevolod G. Potapenko

First Pavlov State Medical University; City Clinical Hospital No. 31

Email: potapenko.vsevolod@mail.ru
ORCID iD: 0000-0003-2985-0503
SPIN-code: 9113-5912

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg; Saint Petersburg

Svetlana V. Khudonogova

North-Western State Medical University named after I.I. Mechnikov

Email: Svetlana.Khudonogova@szgmu.ru
ORCID iD: 0000-0001-5161-8714
SPIN-code: 1613-3189

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Vadim I. Mazurov

North-Western State Medical University named after I.I. Mechnikov

Email: maz.nwgmu@yandex.ru
ORCID iD: 0000-0002-0797-2051
SPIN-code: 6823-5482

MD, Dr. Sci. (Med.), Professor, Academician of the RAS, Honored Scientist of the Russian Federation

Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
Action
1. Fig. 1. Forest graph showing the relationship of various comorbidities with the risk of death. Groups of comorbidity with the highest odds ratios are highlighted in red. CKD — chronic kidney disease; CAD — coronary artery disease; COPD — chronic obstructive pulmonary disease; AH — arterial hypertension; CHF — congestive heart failure; T2D — type 2 diabetes; CM — comorbidity

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2. Fig. 2. Concentration of interleukin 6, interleukin 18, interleukin 10, procalcitonin in the healthy individuals, recovered and the deceased patients with COVID-19-associated pneumonia. IL-6 — interleukin 6, IL-18 — interleukin 18, IL-10 — interleukin 10, PCT — procalcitonin

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3. Fig. 3. ROC curves of the cytokine storm scale, C-reactive protein, lactate hydrogenase, ferritin, D-dimer, neutrophils for predicting the critical course of COVID-19. CS — cytokine storm; CRP — C-reactive protein; LDH — lactatdehydrogenase

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4. Fig. 4. Cytokine storm scale and age (a); Cytokine storm scale and comorbidity (b). CM — comorbitidies; CS — cytokine storm

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Copyright (c) 2021 Tkachenko O.Y., Pervakova M.Y., Lapin S.V., Mazing A.V., Kuznetsova D.A., Moshnikova A.N., Kholopova I.V., Blinova T.V., Surkova E.A., Kulikov A.N., Vorobyev E.A., Vorobyeva S.V., Stanevich O.V., Polushin Y.S., Shlyk I.V., Afanasyev A., Gavrilova E.G., Titova O.N., Volchkova E.V., Potapenko V.G., Khudonogova S.V., Mazurov V.I.

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