Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients

Aysun Hacışevki; Turgut Kaya

doi:10.59124/guhes.1818699

Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients

Abstract

Since the beginning of the 21st century, several infectious disease outbreaks have occurred worldwide, posing serious threats to global health. Among these, the COVID-19 pandemic, which emerged in late 2019, caused millions of deaths and severe strain on healthcare systems. Beyond its respiratory manifestations, COVID-19 has been closely associated with systemic complications, particularly coagulopathy, which represents a major determinant of morbidity and mortality. Coagulopathy in COVID-19 involves abnormal activation of coagulation pathways, leading to microvascular thrombosis and thromboembolic events such as deep vein thrombosis and pulmonary embolism. These complications contribute to hypoxia, multi-organ failure, and increased mortality rates. The mechanisms underlying this hypercoagulable state include endothelial dysfunction, excessive inflammation, oxidative stress, and immune imbalance. A growing body of evidence highlights the crucial role of thiol–disulphide homeostasis in preserving redox balance and vascular integrity. Under oxidative stress, the excessive generation of reactive oxygen species (ROS) alters the thiol–disulphide equilibrium, impairing protein structure and endothelial function. In COVID-19, this imbalance amplifies inflammatory and prothrombotic responses, exacerbating coagulopathy. This review discusses the interplay between coagulopathy and thiol–disulphide homeostasis in COVID-19, emphasizing how redox imbalance contributes to thrombogenesis. Understanding these mechanisms may provide novel insights into potential biomarkers and therapeutic strategies aimed at restoring oxidative balance and preventing thrombotic complications in patients with severe COVID-19.

Keywords

coagulopathy, COVID-19, endothelial dysfunction, oxidative stress, thiol–disulphide, homeostasis

Supporting Institution

No financial support was received for this study.

Ethical Statement

This study is a review study, so it does not require ethics committee approval. However, it was conducted in accordance with ethical principles.

References

Alwazeer, D., Liu, F. F., Wu, X. Y., & LeBaron, T. W. (2021). Combating oxidative stress and inflammation in COVID-19 by molecular hydrogen therapy: mechanisms and perspectives. Oxidative Medicine and Cellular Longevity, 2021, 5513868.https://doi:10.1155/2021/5513868
Bergmann, C. C., & Silverman, R. H. (2020). COVID-19: Coronavirus replication, pathogenesis, and therapeutic strategies. Cleveland Clinic Journal of Medicine, 87(6), 321-327.https://doi:10.3949/ccjm.87a.20047
Bhalla, V., Blish, C. A., & South, A. M. (2021). A historical perspective on ACE2 in the COVID-19 era. Journal of Human Hypertension, 35(10), 935-939.https://doi:10.1038/s41371-020-00459-3
Bhattacharjee, S., Banerjee, M., & Pal, R. (2020). COVID-19 associated hemophagocytic lymphohistiocytosis and coagulopathy: targeting the duumvirate. Indian pediatrics, 57(9), 827-833.https://doi:10.1007/s13312-020-1962-z
Borges do Nascimento, I. J., Cacic, N., Abdulazeem, H. M., von Groote, T. C., Jayarajah, U., Weerasekara, I., et al. (2020). Novel Coronavirus Infection (COVID-19) in humans: a scoping review and meta-analysis. Journal of Clinical Medicine, 9(4).https://doi:10.3390/jcm9040941
Cao, M., Zhang, D., Wang, Y., Lu, Y., Zhu, X., Li, Y., et al. (2020). Clinical features of patients infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China. Lancet, https://doi:10.1101/2020.03.04.20030395
Cazzola, M., Rogliani, P., Salvi, S. S., Ora, J., & Matera, M. G. (2021). Use of thiols in the treatment of covid-19: current evidence. Lung, 199(4), 335-343.https://doi:10.1007/s00408-021-00465-3
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., et al. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 395(10223), 507-513.https://doi:10.1016/s0140-6736(20)30211-7
Chowdary, P. (2022). COVID-19 coagulopathy - what should we treat? Experimental physiology, 107(7), 749-758.https://doi:10.1113/ep089404
Connors, J. M., & Levy, J. H. (2020). COVID-19 and its implications for thrombosis and anticoagulation. Blood, 135(23), 2033-2040.https://doi:10.1182/blood.2020006000

Cucinotta, D., & Vanelli, M. (2020). WHO declares COVID-19 a pandemic. Acta Biomedica, 91(1), 157-160.https://doi:10.23750/abm.v91i1.9397
Duran, E., Taşkın, A., Pehlivan, B., Çelik, H., Pehlivan, V. F., & Taşkın, S. (2022). Dynamic thiol disulphide homeostasis in the follow-up of the prognosis of patients treated for COVID-19 in the intensive care unit. Cureus, 14(7), e27542.https://doi:10.7759/cureus.27542
Erel, Ö., & Erdoğan, S. (2020). Thiol-disulfide homeostasis: an integrated approach with biochemical and clinical aspects. Turkish Journal of Medical Sciences, 50(Si-2), 1728-1738.https://doi:10.3906/sag-2003-64
Fried, J. A., Ramasubbu, K., Bhatt, R., Topkara, V. K., Clerkin, K. J., Horn, E., et al. (2020). The variety of cardiovascular presentations of COVID-19. Circulation, 141(23), 1930-1936.https://doi:10.1161/circulationaha.120.047164
Giustarini, D., Santucci, A., Bartolini, D., Galli, F., & Rossi, R. (2021). The age-dependent decline of the extracellular thiol-disulfide balance and its role in SARS-CoV-2 infection. Redox biology, 41, 101902.https://doi:10.1016/j.redox.2021.101902
Hacışevki, A., & Baba, B. (2020). An overview of vitamins and minerals in the prevention of COVID-19 infection. Gazi Medical Journal, 31.
Iba, T., Connors, J. M., & Levy, J. H. (2020). The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflammation research, 69(12), 1181-1189.https://doi:10.1007/s00011-020-01401-6
Iba, T., Levy, J. H., Maier, C. L., Connors, J. M., & Levi, M. (2024). Four years into the pandemic, managing COVID-19 patients with acute coagulopathy: what have we learned? Journal of Thrombosis and Haemostasis, 22(6), 1541-1549.https://doi:10.1016/j.jtha.2024.02.013
Jevšnik, M., Uršič, T., Zigon, N., Lusa, L., Krivec, U., & Petrovec, M. (2012). Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease. BMC Infectious Diseases, 12, 365.https://doi:10.1186/1471-2334-12-365
Karkhanei, B., Talebi Ghane, E., & Mehri, F. (2021). Evaluation of oxidative stress level: total antioxidant capacity, total oxidant status and glutathione activity in patients with COVID-19. New Microbes and New Infections, 42, 100897.https://doi:10.1016/j.nmni.2021.100897
Kaye, A. D., Okeagu, C. N., Pham, A. D., Silva, R. A., Hurley, J. J., Arron, B. L., et al. (2021). Economic impact of COVID-19 pandemic on healthcare facilities and systems: International perspectives. Best Practice & Research. Clinical Anaesthesiology, 35(3), 293-306.https://doi:10.1016/j.bpa.2020.11.009
Kumar, A., Narayan, R. K., Prasoon, P., Kumari, C., Kaur, G., Kumar, S., et al. (2021). COVID-19 mechanisms in the human body-what we know so far. Frontiers in Immunology, 12, 693938.https://doi:10.3389/fimmu.2021.693938
Kumar, A., Prasoon, P., Kumari, C., Pareek, V., Faiq, M. A., Narayan, R. K., et al. (2021). SARS-CoV-2-specific virulence factors in COVID-19. Journal of Medical Virology, 93(3), 1343-1350.https://doi:10.1002/jmv.26615
Levi, M., Thachil, J., Iba, T., & Levy, J. H. (2020). Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematology, 7(6), e438-e440.https://doi:10.1016/s2352-3026(20)30145-9
Liu, H., Wang, Z., Sun, H., Teng, T., Li, Y., Zhou, X., et al. (2020). Thrombosis and coagulopathy in covid-19: current understanding and implications for antithrombotic treatment in patients treated with percutaneous coronary intervention. Frontiers in Cardiovascular Medicine, 7, 599334.https://doi:10.3389/fcvm.2020.599334
Mohammadinia, L., Saadatmand, V., Khaledi Sardashti, H., Darabi, S., Esfandiary Bayat, F., Rejeh, N., et al. (2023). Hospital response challenges and strategies during COVID-19 pandemic: a qualitative study. Frontiers in Public Health, 11, 1167411.https://doi:10.3389/fpubh.2023.1167411
Özgöçer, T., Çelik, H., & Ceylan, M. R. (2024). Dynamic thiol-disulfide homeostasis post-COVID-19 depends on age, gender, and symptom severity. Cureus, 16(10), e72097.https://doi:10.7759/cureus.72097
Polonikov, A. (2020). Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in COVID-19 patients. ACS Infectection Diseases, 6(7), 1558-1562.https://doi:10.1021/acsinfecdis.0c00288
Santos, R. A. S., Sampaio, W. O., Alzamora, A. C., Motta-Santos, D., Alenina, N., Bader, M., et al. (2018). The ACE2/Angiotensin-(1-7)/MAS Axis of the renin-angiotensin system: focus on angiotensin, (1-7). Physiological Reviews, 98(1), 505-553.https://doi:10.1152/physrev.00023.2016
Sungnak, W., Huang, N., Bécavin, C., Berg, M., Queen, R., Litvinukova, M., et al. (2020). SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine, 26(5), 681-687.https://doi:10.1038/s41591-020-0868-6
van der Hoek, L., Pyrc, K., Jebbink, M. F., Vermeulen-Oost, W., Berkhout, R. J., Wolthers, K. C., et al. (2004). Identification of a new human coronavirus. Nature Medicine, 10(4), 368-373.https://doi:10.1038/nm1024
Wu, F., Zhao, S., Yu, B., Chen, Y. M., Wang, W., Song, Z. G., et al. (2020). A new coronavirus associated with human respiratory disease in China. Nature, 579(7798), 265-269.https://doi:10.1038/s41586-020-2008-3
Yagil, Y., & Yagil, C. (2003). Hypothesis: ACE2 modulates blood pressure in the mammalian organism. Hypertension, 41(4), 871-873.https://doi:10.1161/01.Hyp.0000063886.71596.C8
Yin, Y., & Wunderink, R. G. (2018). MERS, SARS and other coronaviruses as causes of pneumonia. Respirology, 23(2), 130-137.https://doi:10.1111/resp.13196
Zaki, A. M., van Boheemen, S., Bestebroer, T. M., Osterhaus, A. D., & Fouchier, R. A. (2012). Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. The New England Journal of Medicine, 367(19), 1814-1820.https://doi:10.1056/NEJMoa1211721
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., et al. (2020). A Novel Coronavirus from patients with pneumonia in China, 2019. The New England journal of medicine, 382(8), 727-733.https://doi:10.1056/NEJMoa2001017

Details

Primary Language

English

Subjects

Primary Health Care

Journal Section

Review

Authors

Aysun Hacışevki ^*
0000-0002-3844-5772
Türkiye

Turgut Kaya
0000-0002-3533-9157
Türkiye

Publication Date

December 29, 2025

Submission Date

November 6, 2025

Acceptance Date

December 2, 2025

Published in Issue

Year 2025 Volume: 7 Number: 3

DOI

https://doi.org/10.59124/guhes.1818699

IZ

https://izlik.org/JA48UJ37DH

APA

Hacışevki, A., & Kaya, T. (2025). Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients. Journal of Gazi University Health Sciences Institute, 7(3), 105-113. https://doi.org/10.59124/guhes.1818699

AMA

1.Hacışevki A, Kaya T. Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients. GUHES. 2025;7(3):105-113. doi:10.59124/guhes.1818699

Chicago

Hacışevki, Aysun, and Turgut Kaya. 2025. “Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients”. Journal of Gazi University Health Sciences Institute 7 (3): 105-13. https://doi.org/10.59124/guhes.1818699.

EndNote

Hacışevki A, Kaya T (December 1, 2025) Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients. Journal of Gazi University Health Sciences Institute 7 3 105–113.

IEEE

[1]A. Hacışevki and T. Kaya, “Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients”, GUHES, vol. 7, no. 3, pp. 105–113, Dec. 2025, doi: 10.59124/guhes.1818699.

ISNAD

Hacışevki, Aysun - Kaya, Turgut. “Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients”. Journal of Gazi University Health Sciences Institute 7/3 (December 1, 2025): 105-113. https://doi.org/10.59124/guhes.1818699.

JAMA

1.Hacışevki A, Kaya T. Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients. GUHES. 2025;7:105–113.

MLA

Hacışevki, Aysun, and Turgut Kaya. “Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients”. Journal of Gazi University Health Sciences Institute, vol. 7, no. 3, Dec. 2025, pp. 105-13, doi:10.59124/guhes.1818699.

Vancouver

1.Aysun Hacışevki, Turgut Kaya. Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients. GUHES. 2025 Dec. 1;7(3):105-13. doi:10.59124/guhes.1818699

Thiol-Disulphide Homeostasis and Coagulopathy in Covid-19 Patients

Abstract

Keywords

Supporting Institution

Ethical Statement

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

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