Predictors of lethal COVID-19 in patients of intensive care unit

Cover Page

Cite item

Full Text

Abstract

Aim – to identify potential independent routine laboratory predictors of lethal COVID-19 in critically ill patients admitted to the ICU.

Material and methods. This single-centered study included 120 critically ill adult patients with COVID-19 admitted to ICU of the Samara Regional Clinical Hospital named after V.D. Seredavin from August 1 to October 31, 2021. Data on demographics, chest computed tomography, echocardiography, lower extremity venous ultrasound, laboratory tests upon admission to ICU, and clinical outcomes were collected. Data of laboratory tests between survived and deceased patients were compared to identify risk factors of lethality. Univariable and multivariable logistic regression analyses were performed to examine the association of different laboratory parameters with mortality.

Results. As a result of our study, we obtained a multiple logistic regression model that can predict lethal outcomes (AUC=0.820) with relatively high sensitivity (85%) and specificity (85%).

According to our model, elevations in LDH (OR, 0.99; 95% CI, 0.99-1.2), Urea (OR, 0.82; 95% CI, 0.68-0.96), Glucose (OR, 0.99; 95% CI, 0.84-1.15), ASAT (OR, 0.97; 95% CI, 0.94-0.99), and also lymphopenia (lymphocytes count <3.00 × 109/L, OR, 2.53; 95% CI, 0.99-6.93) were predictive for lethal outcome of critically ill COVID-19 patients. Besides, by previously reported data, older age, a high percentage of lung damage on CT, and low heart output also were associated with high mortality risk.

Conclusion. Thus, LDH, Urea, ASAT, Glucose, and lymphocyte levels in COVID-19 patients upon ICU admission should be considered by physicians as independent predictors of the negative outcome.

About the authors

Olesya V. Gubaidullina

Samara State Medical University

Email: manovaolesya@yandex.ru
ORCID iD: 0000-0002-4871-3013

anesthesiologist-intensive care physician

Russian Federation, Samara

Artem V. Aleksankin

Samara State Medical University

Author for correspondence.
Email: aleksankin10@mail.ru
ORCID iD: 0000-0003-4518-9233

Head of the Department of Anesthesiology and Intensive Care No. 2

Russian Federation, Samara

References

  1. WHO Director-General’s opening remarks at the media briefing on COVID19 -March 2020. URL: https://www.who.int/
  2. Coronavirus Cases, Retrieved December 22, 2020. URL: https://www.worldometers.info/coronavirus/
  3. Soneji S, Beltrán-Sánchez H, Yang JW, Mann C. Population-level mortality burden from novel coronavirus (COVID-19) in Europe and North America. Genus. 2021;77(1):7. DOI: https://doi.org/10.1186/s41118-021-00115-9
  4. Simonsen L, Viboud C. A comprehensive look at the COVID-19 pandemic death toll. Elife. 2021;10:e71974. DOI: https://doi.org/10.7554/eLife.71974
  5. Wei C, Lee CC, Hsu TC, et al. Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries. Epidemiol Infect. 2020;149:e1. DOI: https://doi.org/10.1017/S0950268820003076
  6. da Rosa Mesquita R, Francelino Silva Junior LC, Santos Santana FM, et al. Clinical manifestations of COVID-19 in the general population: systematic review. Wien Klin Wochenschr. 2021;133(7-8):377-382. DOI: https://doi.org/10.1007/s00508-020-01760-4
  7. Kutsuna S. Clinical Manifestations of Coronavirus Disease 2019. JMA J. 2021;15;4(2):76-80. DOI: https://doi.org/10.31662/jmaj.2021-0013
  8. Al-Swiahb JN, Motiwala MA. Upper respiratory tract and otolaryngological manifestations of coronavirus disease 2019 (COVID-19): A systemic review. SAGE Open Med. 2021;9:20503121211016965. DOI: https://doi.org/10.1177/20503121211016965
  9. Arentz M, Yim E, Klaff L, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020;323(16):1612-1614. DOI: https://doi.org/10.1001/jama.2020.4326
  10. 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):1054-1062. DOI: https://doi.org/10.1016/S0140-6736(20)30566-3
  11. Auld SC, Harrington KRV, Adelman MW, et al. Emory COVID-19 Quality and Clinical Research Collaborative. Trends in ICU Mortality From Coronavirus Disease 2019: A Tale of Three Surges. Crit Care Med. 2022;50(2):245-255. DOI: https://doi.org/10.1097/CCM.0000000000005185
  12. Zhang JJY, Lee KS, Ang LW, et al. Risk Factors for Severe Disease and Efficacy of Treatment in Patients Infected With COVID-19: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis. Clin Infect Dis. 2020;71(16):2199-2206. DOI: https://doi.org/10.1093/cid/ciaa576
  13. Li J, He X, Yuan Yuan, et al. Meta-analysis investigating the relationship between clinical features, outcomes, and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Am J Infect Control. 2021;49(1):82-89. DOI: https://doi.org/10.1016/j.ajic.2020.06.008
  14. Lu L, Zhong W, Bian Z, et al. A comparison of mortality-related risk factors of COVID-19, SARS, and MERS: A systematic review and meta-analysis. J Infect. 2020;81(4):e18-e25. DOI: https://doi.org/10.1016/j.jinf.2020.07.002
  15. Henry B, Cheruiyot I, Vikse J, et al. Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis. Acta Biomed. 2020;91(3):e2020008. DOI: https://doi.org/10.23750/abm.v91i3.10217
  16. Moutchia J, Pokharel P, Kerri A, et al. Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. PLoS One. 2020;15(10):e0239802. DOI: https://doi.org/10.1371/journal.pone.0239802
  17. Israfil SMH, Sarker MMR, Rashid PT, et al. Clinical Characteristics and Diagnostic Challenges of COVID-19: An Update From the Global Perspective. Front Public Health. 2021;8:567395. DOI: https://doi.org/10.3389/fpubh.2020.567395
  18. Poly TN, Islam MM, Yang HC, et al. Obesity and Mortality Among Patients Diagnosed With COVID-19: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021;8:620044. DOI: https://doi.org/10.3389/fmed.2021.620044
  19. Sharma J, Rajput R, Bhatia M, et al. Clinical Predictors of COVID-19 Severity and Mortality: A Perspective. Front Cell Infect Microbiol. 2021;11:674277. DOI: https://doi.org/10.3389/fcimb.2021.674277
  20. Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802-810. DOI: https://doi.org/10.1001/jamacardio.2020.0950
  21. Grasselli G, Zangrillo A, Zanella A, et al. COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-1581. DOI: https://doi.org/10.1001/jama.2020.5394
  22. Sattar N, Valabhji J. Obesity as a Risk Factor for Severe COVID-19: Summary of the Best Evidence and Implications for Health Care. Curr Obes Rep. 2021;10(3):282-289. DOI: https://doi.org/10.1007/s13679-021-00448-8
  23. Gerayeli FV, Milne S, Cheung C, et al. COPD and the risk of poor outcomes in COVID-19: A systematic review and meta-analysis. E Clinical Medicine. 2021;33:100789. DOI: https://doi.org/10.1016/j.eclinm.2021.100789
  24. Harrison SL, Buckley BJR, Rivera-Caravaca JM, et al. Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews. Eur Heart J Qual Care Clin Outcomes. 2021;7(4):330-339. DOI: https://doi.org/10.1093/ehjqcco/qcab029
  25. Park BE, Lee JH, Park HK, et al. Daegu COVID-19 Research Project. Impact of Cardiovascular Risk Factors and Cardiovascular Diseases on Outcomes in Patients Hospitalized with COVID-19 in Daegu Metropolitan City. J Korean Med Sci. 2021;36(2):e15. DOI: https://doi.org/10.3346/jkms.2021.36.e15
  26. Norouzi M, Norouzi S, Ruggiero A, et al. Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection. Microorganisms. 2021;9(6):1211. DOI: https://doi.org/10.3390/microorganisms9061211
  27. Gangadharan C, Ahluwalia R, Sigamani A. Diabetes and COVID-19: Role of insulin resistance as a risk factor for COVID-19 severity. World J Diabetes. 2021;12(9):1550-1562. DOI: https://doi.org/10.4239/wjd.v12.i9.155
  28. Du Y, Zhou N, Zha W, Lv Y. Hypertension is a clinically important risk factor for critical illness and mortality in COVID-19: A meta-analysis. Nutr Metab Cardiovasc Dis. 2021;31(3):745-755. DOI: https://doi.org/10.1016/j.numecd.2020.12.009
  29. Li G, Xu F, Yin X, et al. Lactic dehydrogenase-lymphocyte ratio for predicting prognosis of severe COVID-19. Medicine (Baltimore). 2021;100(4):e24441. DOI: https://doi.org/10.1097/MD.0000000000024441
  30. Smilowitz NR, Kunichoff D, Garshick M, et al. C-reactive protein and clinical outcomes in patients with COVID-19. Eur Heart J. 2021;42(23):2270-2279. DOI: https://doi.org/10.1093/eurheartj/ehaa110
  31. Hansrivijit P, Gadhiya KP, Gangireddy M, Goldman JD. Risk Factors, Clinical Characteristics, and Prognosis of Acute Kidney Injury in Hospitalized COVID-19 Patients: A Retrospective Cohort Study. Medicines (Basel). 2021;8(1):4. DOI: https://doi.org/10.3390/medicines8010004
  32. Martínez-Urbistondo M, Gutiérrez-Rojas Á, Andrés A, et al. Severe Lymphopenia as a Predictor of COVID-19 Mortality in Immunosuppressed Patients. J Clin Med. 2021;10(16):3595. DOI: https://doi.org/10.3390/jcm10163595
  33. Al-Samkari H, Karp Leaf RS, Dzik WH, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489-500. DOI: https://doi.org/10.1182/blood.2020006520
  34. Basheer M, Saad E, Hagai R, Assy N. Clinical Predictors of Mortality and Critical Illness in Patients with COVID-19 Pneumonia. Metabolites. 2021;11(10):679. DOI: https://doi.org/10.3390/metabo11100679
  35. Gallo Marin B, Aghagoli G, Lavine K, et al. Predictors of COVID-19 severity: A literature review. Rev Med Virol. 2021;31(1):1-10. DOI: https://doi.org/10.1002/rmv.2146
  36. Obando-Pereda G. Can molecular mimicry explain the cytokine storm of SARS-CoV-2?: An in silico approach. J Med Virol. 2021;93(9):5350-5357. DOI: https://doi.org/10.1002/jmv.27040
  37. Mehta P, Fajgenbaum DC. Is severe COVID-19 a cytokine storm syndrome: a hyperinflammatory debate. Curr Opin Rheumatol. 2021;33(5):419-430. DOI: https://doi.org/10.1097/BOR.0000000000000822
  38. Deng H, Tang TX, Chen D, et al. Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies. Pathogens. 2021;10(5):582. DOI: https://doi.org/10.3390/pathogens10050582
  39. Jiang H, Mei YF. SARS-CoV-2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro. Viruses. 2021;13(10):2056. DOI: https://doi.org/10.3390/v13102056
  40. Maruhashi T, Higashi Y. Pathophysiological Association of Endothelial Dysfunction with Fatal Outcome in COVID-19. Int J Mol Sci. 2021;22(10):5131. DOI: https://doi.org/10.3390/ijms22105131
  41. Migliorini F, Torsiello E, Spiezia F, et al. Association between HLA genotypes and COVID-19 susceptibility, severity and progression: a comprehensive review of the literature. Eur J Med Res. 2021;26(1):84. DOI: https://doi.org/10.1186/s40001-021-00563-1
  42. Naemi FMA, Al-Adwani S, Al-Khatabi H, Al-Nazawi A. Association between the HLA genotype and the severity of COVID-19 infection among South Asians. J Med Virol. 2021;93(7):4430-4437. DOI: https://doi.org/10.1002/jmv.27003
  43. Sen SR, Sanders EC, Santos AM, et al. Evidence for Deleterious Antigenic Imprinting in SARS-CoV-2 Immune Response. bioRxiv [Preprint]. 2021:2021.05.21.445201. DOI: https://doi.org/10.1101/2021.05.21.445201
  44. Aydillo T, Rombauts A, Stadlbauer D, et al. Immunological imprinting of the antibody response in COVID-19 patients. Nat Commun. 2021;12(1):3781. DOI: https://doi.org/10.1038/s41467-021-23977-1
  45. Koneru G, Batiha GE, Algammal AM, et al. BCG Vaccine-Induced Trained Immunity and COVID-19: Protective or Bystander? Infect Drug Resist. 2021;14:1169-1184. DOI: https://doi.org/10.2147/IDR.S300162
  46. Sohrabi Y, Dos Santos JC, Dorenkamp M, et al. Trained immunity as a novel approach against COVID-19 with a focus on Bacillus Calmette-Guérin vaccine: mechanisms, challenges and perspectives. Clin Transl Immunology. 2020;9(12):e1228. DOI: https://doi.org/10.1002/cti2.1228
  47. Debisarun PA, Gössling KL, Bulut O, et al. Induction of trained immunity by influenza vaccination - impact on COVID-19. PLoS Pathog. 2021;17(10):e1009928. DOI: https://doi.org/10.1371/journal.ppat.1009928
  48. Liao M, Liu Y, Yuan J, et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020;26(6):842-844. DOI: https://doi.org/10.1038/s41591-020-0901-9
  49. Vázquez-Jiménez A, Avila-Ponce De León UE, Matadamas-Guzman M, et al. On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers. Front Immunol. 2021;12:705646. DOI: https://doi.org/10.3389/fimmu.2021.705646
  50. Otsuka R, Seino KI. Macrophage activation syndrome and COVID-19. Inflamm Regen. 2020;40:19. DOI: https://doi.org/10.1186/s41232-020-00131-w
  51. Iqubal A, Hoda F, Najmi AK, Haque SE. Macrophage Activation and Cytokine Release Syndrome in COVID-19: Current Updates and Analysis of Repurposed and Investigational Anti-Cytokine Drugs. Drug Res (Stuttg). 2021;71(4):173-179. DOI: https://doi.org/10.1055/a-1291-7692
  52. Ackermann M, Anders HJ, Bilyy R, et al. Patients with COVID-19: in the dark-NETs of neutrophils. Cell Death Differ. 2021;28(11):3125-3139. DOI: https://doi.org/10.1038/s41418-021-00805-z
  53. Borges L, Pithon-Curi TC, Curi R, Hatanaka E. COVID-19 and Neutrophils: The Relationship between Hyperinflammation and Neutrophil Extracellular Traps. Mediators Inflamm. 2020;2020:8829674. DOI: https://doi.org/10.1155/2020/8829674
  54. Tan C, Li S, Liang Y, Chen M, Liu J. SARS-CoV-2 viremia may predict rapid deterioration of COVID-19 patients. Braz J Infect Dis. 2020;24(6):565-569. DOI: https://doi.org/10.1016/j.bjid.2020.08.010
  55. Filipovic N, Saveljic I, Hamada K, Tsuda A. Abrupt Deterioration of COVID-19 Patients and Spreading of SARS COV-2 Virions in the Lungs. Ann Biomed Eng. 2020;48(12):2705-2706. DOI: https://doi.org/10.1007/s10439-020-02676-w
  56. Hoepel W, Chen HJ, Geyer CE, et al. High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages. Sci Transl Med. 2021;13(596):eabf8654. DOI: https://doi.org/10.1126/scitranslmed.abf8654
  57. Bye AP, Hoepel W, Mitchell JL, et al. Aberrant glycosylation of anti-SARS-CoV-2 spike IgG is a prothrombotic stimulus for platelets. Blood. 2021;138(16):1481-1489. DOI: https://doi.org/10.1182/blood.2021011871

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Figure 1. Single-variant logistic regression and ROC analysis of lymphocyte levels and neutrophil-lymphocyte index.

Download (209KB)
3. Figure 2. Single-variant logistic regression (AG) and ROC analysis (H) for various biochemical parameters.

Download (585KB)
4. Figure 3. Multivariate logistic regression and ROC analysis (A) based on LDH, urea, glucose, lymphocytes and ASAT levels.

Download (144KB)

Copyright (c) 2024 Gubaidullina O.V., Aleksankin A.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».