Original Articles

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

Abstract

Objectives: Alpha 1-antitrypsin (A1AT) is a single-chain glycoprotein containing 394 amino acids. It is primarily synthesized in the liver as an acute phase protein. According to recent studies, the Covid-19 virus can infect host cells by binding to the ACE2 receptor via a membrane protein. On the other hand, A1AT has the potential to inhibit neutrophil elastase and prevent the entry of the virus into host cells. Consequently, A1AT can reduce the severity and duration of Covid-19 disease.

Methods: Thirty-one hospitalized Covid-19 patients with a positive PCR test and thirty healthy volunteers with a negative test as the control group were selected. Upon hospitalization, demographic and biochemical tests were conducted for both patients and controls. Serum A1AT levels in both groups were measured using nephelometry as the reference method. Liver enzymes and total protein were also determined using commercially available kits.

Results: Serum A1AT levels in the patients were increased compared to the control group and this increase was inversely proportional to the duration of hospitalization and the relative improvement for discharge. Additionally, this elevation was correlated with qualitative C-reactive protein (CRP) levels. Serum liver enzymes, ALP, and LDH in patients were significantly higher than in the controls (P<0.05), while serum total protein in patients was significantly lower than in the controls (P<0.05).

Conclusion: These data belong to a homologous group and show a correlation between serum A1AT levels and the duration of hospitalization, as well as with qualitative CRP levels. Furthermore, the increase in A1AT is proportional to the levels of serum AST, ALT, total protein, ALP, and LDH, which may serve as an alarm for potential liver involvement in such a disease. Thus, monitoring the liver condition is warranted. 

1. de Loyola MB, Dos Reis TTA, de Oliveira GXLM, da Fonseca Palmeira J, Argañaraz GA, Argañaraz ER. Alpha‐1‐antitrypsin: a possible host protective factor against Covid‐19. Reviews in medical virology. 2021;31(2):e2157. https:// DOI: 10.1002/rmv.2157.
2. Wang M-Y, Zhao R, Gao L-J, Gao X-F, Wang D-P, Cao J-M. SARS-CoV-2: structure, biology, and structure-based therapeutics development. Frontiers in cellular and infection microbiology. 2020;10:587269. https:// DOI: 10.3389/fcimb.2020.587269.
3. Huang Y, Yang C, Xu X-f, Xu W, Liu S-w. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacologica Sinica. 2020;41(9):1141-9. https:// DOI: 10.1038/s41401-020-0485-4.
4. Yang C, Chapman KR, Wong A, Liu M. α1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action. The Lancet Respiratory Medicine. 2021;9(4):337-9. https:// DOI: 10.1016/S2213-2600(21)00018-7.
5. Hassan WN, Najm MA, Hasan AH, Oudah KH. Immunological aspects of Alpha 1- antitrypsin in COVID-19 infection among the Populace and Pregnant Women: Alpha 1- antitrypsin and COVID-19. Al-Kindy College Medical Journal. 2021;17(1):8-13.
6. Carrell RW, Jeppsson JO, Laurell CB, Brennan SO, Owen MC, Vaughan L, et al. Structure and variation of human alpha 1-antitrypsin. Nature. 1982;298(5872):329-34. https:// DOI: 10.1038/298329a0.
7. Cox DW, Johnson AM, Fagerhol MK. Report of Nomenclature Meeting for alpha 1-antitrypsin, INSERM, Rouen/Bois-Guillaume-1978. Human genetics. 1980;53(3):429-33. https:// DOI: 10.1007/BF00287070.
8. Johnson D, Travis J. The oxidative inactivation of human alpha-1-proteinase inhibitor. Further evidence for methionine at the reactive center. Journal of Biological Chemistry. 1979;254(10):4022-6. https://doi.org/10.1016/S0021-9258(18)50689-X.
9. Fayes K C, G. HL. Alpha 1 antutrypsin deficiency Metabolic basis of inheritted diseases. 1989.
10. de Serres F, Blanco I. Role of alpha-1 antitrypsin in human health and disease. Journal of internal medicine. 2014;276(4):311-35.https:// DOI: 10.1111/joim.12239.
11. Rodríguez Hermosa JL, et al. Severe COVID-19 Illness and α1-Antitrypsin Deficiency: COVID-AATD Study. Biomedicines. 2023 Feb 10;11(2):516. doi: 10.3390/biomedicines11020516.
12. Feng G, Zheng KI, Yan Q-Q, Rios RS, Targher G, Byrne CD, et al. COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies. Journal of clinical and translational hepatology. 2020;8(1):18.https:// DOI: 10.14218/JCTH.2020.00018.
13. Baroiu L, Dumitru C, Iancu A, Leșe A-C, Drăgănescu M, Baroiu N, et al. COVID-19 impact on the liver. World Journal of Clinical Cases. 2021;9(16):3814. https:// DOI: 10.12998/wjcc.v9.i16.3814.
14. Pérez JMH, Gonçálves JMF, Fariña YR. Alpha-1 antitrypsin as a risk marker in SARS-CoV-2 infection. Archives of Medical Science: AMS. 2021;17(4):1134. https:// DOI: 10.5114/aoms/136562.
15. Janciauskiene S, Welte T. Well-known and less well-known functions of alpha-1 antitrypsin. Its role in chronic obstructive pulmonary disease and other disease developments. Annals of the American Thoracic Society. 2016;13(Supplement4):S280-S8. https:// DOI: 10.1513/AnnalsATS.201507-468KV.
16. Guttman O, Baranovski B, Schuster R, Kaner Z, Freixo-Lima G, Bahar N, et al. Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats. Clinical & Experimental Immunology. 2015;179(2):161-72. https:// DOI: 10.1111/cei.12476.
17. Sandford AJ, Chagani T, Spinelli JJ, Pare PD. α1-antitrypsin genotypes and the acute-phase response to open heart surgery. American journal of respiratory and critical care medicine. 1999;159(5):1624-8. https:// DOI: 10.1164/ajrccm.159.5.9711004.
18. Buttenschoen K, Buttenschoen DC, Berger D, Vasilescu C, Schafheutle S, Goeltenboth B, et al. Endotoxemia and acute-phase proteins in major abdominal surgery. The American journal of surgery. 2001;181(1):36-43. https:// DOI: 10.1016/s0002-9610(00)00534-1.
19. Ziakas AG, Koskinas KC, Souliou E, Gavrilidis S, Giannoglou GD, Gemitzis K, et al. Serial measurements of acute phase proteins in patients with acute coronary syndrome. Hellenic J Cardiol. 2011;52(4):293-8.
20. Shapiro L, B. Pott G, H. Ralston A. Alpha‐1‐antitrypsin inhibits human immunodeficiency virus type 1. The FASEB Journal. 2001;15(1):115-22. https:// DOI: 10.1096/fj.00-0311com.
21. Münch J, Ständker L, Adermann K, Schulz A, Schindler M, Chinnadurai R, et al. Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide. Cell. 2007;129(2):263-75. https:// DOI: 10.1016/j.cell.2007.02.042.
22. Wanner A, Arce AD, Pardee E. Novel therapeutic uses of alpha-1 antitrypsin: a window to the future. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2012;9(6):583-8. https:// DOI: 10.3109/15412555.2012.717125.
23. Yang C, Keshavjee S, Liu M. Alpha-1 antitrypsin for COVID-19 treatment: dual role in antiviral infection and anti-inflammation. Frontiers in Pharmacology. 2020;11:615398. https:// DOI: 10.3389/fphar.2020.615398.
24. Vianello A, Braccioni F. Geographical overlap between alpha-1 antitrypsin deficiency and COVID-19 infection in Italy: casual or causal? Archivos de bronconeumologia. 2020;56(9):609.
25. 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: 10.1002/hep.31301.
26. Przekop D, Gruszewska E, Chrostek L. Liver function in COVID-19 infection. World Journal of Hepatology. 2021;13(12):1909. https:// DOI: 10.4254/wjh.v13.i12.1909.
27. Dinevari MF, Somi MH, Majd ES, Fattahzadeh A, Nikniaz Z. Elevated Liver Aminotransferases Level and COVID-19 Prognosis in Hospitalized Patients: A Prospective Study from Iran. Middle East Journal of Digestive Diseases (MEJDD). 2022;14(1):64-9. https:// DOI: 10.34172/mejdd.2022.257.
28. Han Y, Zhang H, Mu S, Wei W, Jin C, Tong C, et al. Lactate dehydrogenase, an independent risk factor of severe COVID-19 patients: a retrospective and observational study. Aging (Albany NY). 2020;12(12):11245. https:// DOI: 10.18632/aging.103372.
29. Henry BM, Aggarwal G, Wong J, Benoit S, Vikse J, Plebani M, et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis. The American journal of emergency medicine. 2020;38(9):1722-6. https:// DOI: 10.1016/j.ajem.2020.05.073.
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IssueVol 2 No 2 (2024): . QRcode
SectionOriginal Articles
DOI https://doi.org/10.18502/abi.v2i2.17936
Keywords
Alpha 1-antitrypsin Covid-19 Serum proteins AST ALT Total protein ALP

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1.
Salehi M, Sahebghadam Lotfi A. 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. ABI. 2024;2(2):96-102.