Effects of COVID-19 Infection on Biochemical Parameters and Biomarkers Associated with Disease Prognosis and Severity
-
Hamidreza Shiri
,
Ali Akbar Soleimani
,
Behnam Omidi Sarajar
,
Ghodratollah Panahi
,
Sina Habibi
,
Mohammad Hadi Nematollahi
Abstract
Objectives: COVID-19 is a disease associated with biochemical disruptions. This study aimed to evaluate changes in biochemical parameters in COVID-19 patients and to identify clinically applicable biomarkers for disease prognosis and severity assessment.
Methods: This study enrolled 155 hospitalized COVID-19 patients classified as mild (n=35), moderate (n=40), severe (n=35), or critical (n=45), along with 40 healthy controls. Serum levels of blood glucose (BG), blood urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T‑Bil), direct bilirubin (D‑Bil), lactate dehydrogenase (LDH), high‑sensitivity C‑reactive protein (hs‑CRP), and electrolytes (Na⁺, K⁺) were measured. Logistic regression was performed to assess disease severity. Receiver operating characteristic (ROC) curve analyses were conducted to identify independent predictors and optimal cut‑off values for prognosis (patients vs. controls) and severity (mild vs. moderate, severe, and critical groups).
Results: All hepatic, renal, and glycemic parameters, as well as LDH and hs‑CRP, were elevated across all patient groups compared to controls (P < 0.001). Adjusted logistic regression identified hs‑CRP (odds ratio (OR) = 25.76), D‑Bil (OR = 4.56), Cr (OR = 3.17), and LDH (OR = 1.26) as the strongest independent predictors of increased infection severity. ROC analysis determined LDH as the best biomarker for disease prognosis (AUC = 97.72%, cut‑off > 317 U/L) and D‑Bil for disease severity (AUC = 72.81%, cut‑off > 0.23 mg/dL).
Conclusion: LDH and D‑Bil represent the most clinically useful biomarkers for COVID‑19 prognosis and severity detection, respectively. These results advocate for their routine integration into standard biochemical surveillance to facilitate early risk assessment; however, broader prospective investigations with larger cohorts are essential to confirm their generalizability.
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19. Laguna-Goya R, Utrero-Rico A, Talayero P, Lasa-Lazaro M, Ramirez-Fernandez A, Naranjo L, et al. IL-6-based mortality risk model for hospitalized patients with COVID-19. J Allergy Clin Immunol. 2020;146(4):799-807 e9. https://doi.org/10.1016/j.jaci.2020.07.009.
20. Bastin A, Shiri H, Zanganeh S, Fooladi S, Momeni Moghaddam MA, Mehrabani M, Nematollahi MH. Iron Chelator or Iron Supplement Consumption in COVID-19? The Role of Iron with Severity Infection. Biol Trace Elem Res. 2022;200(11):4571-81. https://doi.org/10.1007/s12011-021-03048-8.
21. Gandhi RT, Lynch JB, Del Rio C. Mild or Moderate Covid-19. N Engl J Med. 2020;383(18):1757-66. https://doi.org/10.1056/NEJMcp2009249.
22. Asadikaram G, Ram M, Izadi A, Sheikh Fathollahi M, Nematollahi MH, Najafipour H, et al. The study of the serum level of IL‐4, TGF‐β, IFN‐γ, and IL‐6 in overweight patients with and without diabetes mellitus and hypertension. J Cell Biochem. 2019;120(3):4147-57. https://doi.org//10.1002/jcb.27700
23. Sedaghat MR, Shiri H, Tavakkol-Afshari J, Norouzmahani ME, Bahri F, Fooladi S, et al. Impact of a 50bp insertion/deletion polymorphism of the superoxide dismutase-1 on oxidative stress status and risk of keratoconus. Exp Eye Res. 2024;238:109742. https://doi.org/10.1016/j.exer.2023.109742.
24. 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. https://doi.org/10.1016/S0140-6736(20)30183-5.
25. Gupta R, Ghosh A, Singh AK, Misra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes Metab Syndr. 2020;14(3):211-2. https://doi.org/10.1016/j.dsx.2020.03.002.
26. Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, et al. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metab. 2020;31(6):1068-77 e3. https://doi.org/10.1016/j.cmet.2020.04.021.
27. Zahedi M, Kordrostami S, Kalantarhormozi M, Bagheri M. A Review of Hyperglycemia in COVID-19. Cureus. 2023;15(4):e37487. https://doi.org/10.7759/cureus.37487.
28. Nadim MK, Forni LG, Mehta RL, Connor MJ, Jr., Liu KD, Ostermann M, et al. Publisher Correction: COVID-19-associated acute kidney injury: consensus report of the 25(th) Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Nephrol. 2020;16(12):765. https://doi.org/10.1038/s41581-020-00372-5.
29. Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. Lancet Respir Med. 2020;8(7):738-42. https://doi.org/10.1016/S2213-2600(20)30229-0.
30. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5(5):428-30. https://doi.org/10.1016/S2468-1253(20)30057-1.
31. Phipps MM, Barraza LH, LaSota ED, Sobieszczyk ME, Pereira MR, Zheng EX, et al. Acute Liver Injury in COVID-19: Prevalence and Association with Clinical Outcomes in a Large U.S. Cohort. Hepatology. 2020;72(3):807-17. https://doi.org/10.1002/hep.31404.
32. Serra F, Bonaduce I, De Ruvo N, Cautero N, Brugioni L, Gelmini R. Covid-19 and hepatic injury: A systematic review. Clin Res Hepatol Gastroenterol. 2021;45(3):101605. https://doi.org/10.1016/j.clinre.2020.101605.
33. Lei F, Liu YM, Zhou F, Qin JJ, Zhang P, Zhu L, et al. Longitudinal Association Between Markers of Liver Injury and Mortality in COVID-19 in China. Hepatology. 2020;72(2):389-98. https://doi.org/10.1002/hep.31301.
34. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-43. https://doi.org/10.1038/s41591-020-1051-9.
35. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, 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. https://doi.org/10.1016/S0140-6736(20)30566-3.
36. Yousaf Z, Al-Shokri SD, Al-Soub H, Mohamed MFH. COVID-19-associated SIADH: a clue in the times of pandemic! Am J Physiol Endocrinol Metab. 2020;318(6):E882-E5. https://doi.org/10.1152/ajpendo.00178.2020.
37. Alfano G, Ferrari A, Fontana F, Perrone R, Mori G, Ascione E, et al. Hypokalemia in Patients with COVID-19. Clin Exp Nephrol. 2021;25(4):401-9. https://doi.org/10.1007/s10157-020-01996-4.
2. Hosseini H, Rohani-Rasaf M, Vatannejad A, Shabani M, Teimouri M. Assessment of leukocyte subtypes to high-density lipoprotein-cholesterol (HDL-C) ratios as predictors of severity and mortality in COVID-19 patients. Acta Biochim Iran. 2023;1(3):133-8. https://doi.org/10.18502/abi.v1i3.14549
3. Salehi M, Lotfi AS. Alpha 1-antitrypsin as a potent biomarker for monitoring of disease severity in patients with Covid-19 and its correlation with Liver Enzymes and Lactate Dehydrogenase. Acta Biochim Iran. 2024. https://doi.org/10.18502/abi.v2i2.17936
4. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-32. https://doi.org/10.1038/s41591-020-0968-3.
5. Abbaszadeh-Goudarzi K, Nematollahi MH, Khanbabaei H, Nave HH, Mirzaei HR, Pourghadamyari H, Sahebkar A. Targeted delivery of CRISPR/Cas13 as a promising therapeutic approach to treat SARS-CoV-2. Curr Pharm Biotechnol. 2021;22(9):1149-55. https://doi.org/10.2174/1389201021666201009154517
6. Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global prevalence of post-acute sequelae of COVID-19 (PASC) or long COVID: a meta-analysis and systematic review. MedRxiv. 2021:2021.11. 15.21266377. https://doi.org/10.1101/2021.11.15.21266377
7. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58(7):1021-8. https://doi.org/10.1515/cclm-2020-0369.
8. Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T. How COVID-19 induces cytokine storm with high mortality. Inflamm Regen. 2020;40(1):37. https://doi.org/10.1186/s41232-020-00146-3.
9. Siu KL, Yuen KS, Castano-Rodriguez C, Ye ZW, Yeung ML, Fung SY, et al. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. FASEB J. 2019;33(8):8865-77. https://doi.org/10.1096/fj.201802418R.
10. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, Hlh Across Speciality Collaboration UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4. https://doi.org/10.1016/S0140-6736(20)30628-0.
11. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia - A systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14(4):395-403. https://doi.org/10.1016/j.dsx.2020.04.018.
12. Apicella M, Campopiano MC, Mantuano M, Mazoni L, Coppelli A, Del Prato S. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020;8(9):782-92. https://doi.org/10.1016/S2213-8587(20)30238-2.
13. Kulkarni AV, Kumar P, Tevethia HV, Premkumar M, Arab JP, Candia R, et al. Systematic review with meta-analysis: liver manifestations and outcomes in COVID-19. Aliment Pharmacol Ther. 2020;52(4):584-99. https://doi.org/10.1111/apt.15916.
14. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97(5):829-38. https://doi.org/10.1016/j.kint.2020.03.005.
15. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020;58(7):1131-4. https://doi.org/10.1515/cclm-2020-0198.
16. Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia. 2020;63(8):1500-15. https://doi.org/10.1007/s00125-020-05180-x.
17. Hirsch JS, Ng JH, Ross DW, Sharma P, Shah HH, Barnett RL, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020;98(1):209-18. https://doi.org/10.1016/j.kint.2020.05.006.
18. Chen D, Li X, Song Q, Hu C, Su F, Dai J, et al. Hypokalemia and clinical implications in patients with coronavirus disease 2019 (COVID-19). MedRxiv. 2020:2020.02. 27.20028530. https://doi.org/10.1101/2020.02.27.20028530
19. Laguna-Goya R, Utrero-Rico A, Talayero P, Lasa-Lazaro M, Ramirez-Fernandez A, Naranjo L, et al. IL-6-based mortality risk model for hospitalized patients with COVID-19. J Allergy Clin Immunol. 2020;146(4):799-807 e9. https://doi.org/10.1016/j.jaci.2020.07.009.
20. Bastin A, Shiri H, Zanganeh S, Fooladi S, Momeni Moghaddam MA, Mehrabani M, Nematollahi MH. Iron Chelator or Iron Supplement Consumption in COVID-19? The Role of Iron with Severity Infection. Biol Trace Elem Res. 2022;200(11):4571-81. https://doi.org/10.1007/s12011-021-03048-8.
21. Gandhi RT, Lynch JB, Del Rio C. Mild or Moderate Covid-19. N Engl J Med. 2020;383(18):1757-66. https://doi.org/10.1056/NEJMcp2009249.
22. Asadikaram G, Ram M, Izadi A, Sheikh Fathollahi M, Nematollahi MH, Najafipour H, et al. The study of the serum level of IL‐4, TGF‐β, IFN‐γ, and IL‐6 in overweight patients with and without diabetes mellitus and hypertension. J Cell Biochem. 2019;120(3):4147-57. https://doi.org//10.1002/jcb.27700
23. Sedaghat MR, Shiri H, Tavakkol-Afshari J, Norouzmahani ME, Bahri F, Fooladi S, et al. Impact of a 50bp insertion/deletion polymorphism of the superoxide dismutase-1 on oxidative stress status and risk of keratoconus. Exp Eye Res. 2024;238:109742. https://doi.org/10.1016/j.exer.2023.109742.
24. 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. https://doi.org/10.1016/S0140-6736(20)30183-5.
25. Gupta R, Ghosh A, Singh AK, Misra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes Metab Syndr. 2020;14(3):211-2. https://doi.org/10.1016/j.dsx.2020.03.002.
26. Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, et al. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metab. 2020;31(6):1068-77 e3. https://doi.org/10.1016/j.cmet.2020.04.021.
27. Zahedi M, Kordrostami S, Kalantarhormozi M, Bagheri M. A Review of Hyperglycemia in COVID-19. Cureus. 2023;15(4):e37487. https://doi.org/10.7759/cureus.37487.
28. Nadim MK, Forni LG, Mehta RL, Connor MJ, Jr., Liu KD, Ostermann M, et al. Publisher Correction: COVID-19-associated acute kidney injury: consensus report of the 25(th) Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Nephrol. 2020;16(12):765. https://doi.org/10.1038/s41581-020-00372-5.
29. Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. Lancet Respir Med. 2020;8(7):738-42. https://doi.org/10.1016/S2213-2600(20)30229-0.
30. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5(5):428-30. https://doi.org/10.1016/S2468-1253(20)30057-1.
31. Phipps MM, Barraza LH, LaSota ED, Sobieszczyk ME, Pereira MR, Zheng EX, et al. Acute Liver Injury in COVID-19: Prevalence and Association with Clinical Outcomes in a Large U.S. Cohort. Hepatology. 2020;72(3):807-17. https://doi.org/10.1002/hep.31404.
32. Serra F, Bonaduce I, De Ruvo N, Cautero N, Brugioni L, Gelmini R. Covid-19 and hepatic injury: A systematic review. Clin Res Hepatol Gastroenterol. 2021;45(3):101605. https://doi.org/10.1016/j.clinre.2020.101605.
33. Lei F, Liu YM, Zhou F, Qin JJ, Zhang P, Zhu L, et al. Longitudinal Association Between Markers of Liver Injury and Mortality in COVID-19 in China. Hepatology. 2020;72(2):389-98. https://doi.org/10.1002/hep.31301.
34. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-43. https://doi.org/10.1038/s41591-020-1051-9.
35. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, 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. https://doi.org/10.1016/S0140-6736(20)30566-3.
36. Yousaf Z, Al-Shokri SD, Al-Soub H, Mohamed MFH. COVID-19-associated SIADH: a clue in the times of pandemic! Am J Physiol Endocrinol Metab. 2020;318(6):E882-E5. https://doi.org/10.1152/ajpendo.00178.2020.
37. Alfano G, Ferrari A, Fontana F, Perrone R, Mori G, Ascione E, et al. Hypokalemia in Patients with COVID-19. Clin Exp Nephrol. 2021;25(4):401-9. https://doi.org/10.1007/s10157-020-01996-4.
| Files | ||
| Issue | Vol 2026 No 4 (2) | |
| Section | Original Articles | |
| Keywords | ||
| COVID-19 Biochemical Parameters Disease Prognosis Disease Severity Lactate Dehydrogenase Direct Bilirubin | ||
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How to Cite
1.
Shiri H, Soleimani AA, Omidi Sarajar B, Panahi G, Habibi S, Nematollahi MH. Effects of COVID-19 Infection on Biochemical Parameters and Biomarkers Associated with Disease Prognosis and Severity. ABI. 2026;2026(4):80-88.
