Severe Acute Respiratory Syndrome Coronavirus 2 Infection is Associated with Homocysteine Level and Clinical Outcomes in Ischemic Stroke Patients

Authors

  • Syahrul Syahrul Department of Neurology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
  • Imran Imran Department of Neurology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
  • Nasrul Musadir Department of Neurology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
  • Vivi Keumala Mutiawati Department of Clinical Pathology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.8243

Keywords:

Coronavirus disease 2019, Homocysteine, Ischemic stroke, Risk factor, Predictor

Abstract

BACKGROUND: Since its emergence in December 2019 and declared as pandemic in March 2020, the drastic increase in cases of coronavirus disease 2019 (COVID-19) is alarming the importance of disease monitoring in order to prevent further complication, like ischemic stroke. One of the efforts is utilizing biomarker. For instance, elevated homocysteine level, already known risk factor of ischemic stroke, is currently identified in COVID-19 patients.

AIM: To assess factor associated with homocysteine level and clinical outcomes of ischemic stroke patients.

Methods: A cross-sectional study was conducted at Dr. Zainoel Abidin Hospital di Indonesia between March and August 2021. Ischemic stroke patients who had physical and neurology examinations, SARS-CoV-2 RT-PCR swab, chest x-ray, electrocardiography, head CT-scan and the total homocysteine level were included. To assess the factors associated with homocysteine level and the outcomes of ischemic stroke patients, the independent Student t-test or Anova and chi-squared were used, respectively.

RESULTS: We included 62 ischemic stroke patients of which 32 (51.6%) were male and the age ranged between 30 and 80 years. Out of total, 60 patients (96.8%) were survived after the hospital admission. There was a significant association between gender and having COVID-19 with homocysteine level (p=0.012 and p=0.020, respectively). Having COVID-19 was the only variable significantly associated with the outcome of the ischemic stroke patient (p=0.035).

CONCLUSION: COVID-19 is associated with homocysteine level and the clinical outcome in ischemic stroke patients. Therefore, SARS-CoV-2 infection in ischemic stroke or vice versa need to be monitored closely in hospital settings.

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References

Nassereddine SH, Slama S, Sen K, Rizk A, Sibai AM. COVID-19 and non-communicable diseases in the Eastern Mediterranean Region: The need for a syndemics approach to data reporting and healthcare delivery. BMJ Global Health. 2021;6:e006189. DOI: https://doi.org/10.1136/bmjgh-2021-006189

Rosiello D, Anwar S, Yufika A, Adam R, Ismaeil M. Acceptance of COVID-19 vaccination at different hypothetical efficacy and safety levels in ten countries in Asia, Africa, and South America. Narra J. 2021;1(3):e55. https://doi.org/10.52225/narra.v1i3.55 DOI: https://doi.org/10.52225/narra.v1i3.55

Hassan W, Kazmi SK, Tahir MJ, Ullah I, Royan HA, Fahriani M, et al. Global acceptance and hesitancy of COVID-19 vaccination: A narrative review. Narra J. 2021;1(3):57. https://doi.org/10.52225/narra.v1i3.57 DOI: https://doi.org/10.52225/narra.v1i3.57

Lazarus JV, Ratzan SC, Palayew A, Gostin LO, Larson HJ, Rabin K, et al. A global survey of potential acceptance of a COVID-19 vaccine. Nat Med. 2021;27(2):225-8. https://doi. org/10.1038/s41591-020-1124-9 PMid:33082575 DOI: https://doi.org/10.1038/s41591-020-1124-9

Fajar JK, Ilmawan M, Mamada S, Mutiawati E, Husnah M, Yusuf H, et al. Global prevalence of persistent neuromuscular symptoms and the possible pathomechanisms in COVID-19 recovered individuals: A systematic review and meta-analysis. Narra J. 2021;1(3):e48. https://doi.org/10.52225/narra.v1i3.48 DOI: https://doi.org/10.52225/narra.v1i3.48

Fahriani M, Ilmawan M, Fajar JK, Maliga HA, Frediansyah A, Masyeni S, et al. Persistence of long COVID symptoms in COVID-19 survivors worldwide and its potential pathogenesis-a systematic review and meta-analysis. Narra J. 2021;1(2):e36. DOI: https://doi.org/10.52225/narraj.v1i2.36

Azzini SR, Polito A. Homocysteine: Its possible emerging role in at-risk population groups. Int J Mol Sci. 2020;21(4):1421. https://doi.org/10.3390/ijms21041421 PMid:32093165 DOI: https://doi.org/10.3390/ijms21041421

Spence JD, de Freitas GR, Pettigrew LC, Ay H, Liebeskind DS, Kase CS, et al. Mechanisms of stroke in COVID-19. Cerebrovasc Dis. 2020;49(4):451-8. https://doi.org/10.1159/000509581 PMid:32690850 DOI: https://doi.org/10.1159/000509581

Qureshi AI, Abd-Allah F, Al-Senani F, Aytac E, Borhani- Haghighi A, Ciccone A, et al. Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel. Int J Stroke. 2020;15(5):540-54. PMid:32362244 DOI: https://doi.org/10.1177/1747493020923234

Qureshi AI, Baskett WI, Huang W, Shyu D, Myers D, Raju M, et al. Acute ischemic stroke and COVID-19: An analysis of 27,676 patients. Stroke. 2021;52(3):905-12. https://doi.org/10.1161/STROKEAHA.120.031786 PMid:33535779 DOI: https://doi.org/10.1161/STROKEAHA.120.031786

Mutairi FA. Hyperhomocysteinemia: Clinical insights. J Cent Nerv Syst Dis. 2020;12:1-8. https://doi.org/10.1177/1179573520962230 PMid:33100834 DOI: https://doi.org/10.1177/1179573520962230

Ponti CR, Tomasi A. Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19. Med Hypotheses. 2020;143:109859. https://doi.org/10.1016/j.mehy.2020.109859 PMid:32464494

Guo H, Chi J, Xing Y, Wang P. Influence of folic acid on plasma homocysteine levels and arterial endothelial function in patients with unstable angina. Indian J Med Res. 2009;129(3):279-85. PMid:19491420

Abu-Farha M, Al-Sabah S, Hammad MM, Hebbar P, Channanath AM, John SE, et al. Prognostic genetic markers for thrombosis in COVID-19 patients: A focused analysis on d-dimer, homocysteine and thromboembolism. Front Pharmacol. 2020;11:587451. https://doi.org/10.3389/fphar.2020.587451 PMid:33362545 DOI: https://doi.org/10.3389/fphar.2020.587451

Ponti G, Roli L, Oliva G, Manfredini M, Trenti T, Kaleci S, et al. Homocysteine (Hcy) assessment to predict outcomes of hospitalized Covid-19 patients: A multicenter study on 313 Covid-19 patients. Clin Chem Lab Med. 2021;59(9):e354-7. https://doi.org/10.1515/cclm-2021-0168 PMid:33768762 DOI: https://doi.org/10.1515/cclm-2021-0168

Ponti G, Ruini C, Tomasi A. Homocysteine as a potential predictor of cardiovascular risk in patients with COVID-19. Med Hypotheses. 2020;143:109859. PMid:32464494 DOI: https://doi.org/10.1016/j.mehy.2020.109859

Shi YG, Huo YR, Liu S, Zhang M, Lu H, Yue W, et al. Elevated total homocysteine levels in acute ischemic stroke are associated with long-term mortality. Stroke. 2015;46:2419-25. https://doi.org/10.1161/STROKEAHA.115.009136 PMid:26199315 DOI: https://doi.org/10.1161/STROKEAHA.115.009136

Calmettes J, Peres R, Goncalves B, Varlan D, Turc G, Obadia M, et al. Clinical outcome of acute ischemic strokes in patients with COVID-19. Cerebrovasc Dis. 2021;50(4):412-9. https://doi.org/10.1159/000514562 PMid:33784669 DOI: https://doi.org/10.1159/000514562

Martí-Fàbregas J, Guisado-Alonso D, Delgado-Mederos R, Martínez-Domeño A, Prats-Sánchez L, Guasch-Jiménez M, et al. Impact of COVID-19 infection on the outcome of patients with ischemic stroke. Stroke. 2021;52(12):3908-17. https://doi.org/10.1161/STROKEAHA.121.034883 PMid:34455823 DOI: https://doi.org/10.1161/STROKEAHA.121.034883

Harrison SL, Fazio-Eynullayeva E, Lane DA, Underhill P, Lip GY. Higher mortality of ischaemic stroke patients hospitalized with COVID-19 compared to historical controls. Cerebrovasc Dis. 2021;50(3):326-31. DOI: https://doi.org/10.1159/000514137

Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ. 2020;368:m1295. https://doi.org/10.1136/bmj.m1295 PMid:32234718 DOI: https://doi.org/10.1136/bmj.m1295

Piliszek AW, Sklinda K, Szary C, Ryglewicz D, Dorobek M, Walecki J. Comprehensive imaging of stroke looking for the gold standard. Neurol Neurochir Pol. 2016;50(4):241-50. PMid:27375137 DOI: https://doi.org/10.1016/j.pjnns.2016.04.009

Yi X, Luo H, Zhou J, Yu M, Chen X, Tan L, et al. Prevalence of stroke and stroke related risk factors: A population based cross sectional survey in Southwestern China. BMC Neurol. 2020;20(5):5. https://doi.org/10.1186/s12883-019-1592-z PMid:31910820 DOI: https://doi.org/10.1186/s12883-019-1592-z

Dinavahi RF. Relationship of homocysteine with cardiovascular disease and blood pressure. J Clin Hypertens (Greenwich). 2004;6(9):494-8. https://doi.org/10.1111/j.1524-6175.2004.03643.x PMid:15365276 DOI: https://doi.org/10.1111/j.1524-6175.2004.03643.x

Chen CW, Lin TK, Lin CT, Chen BC. Total cardiovascular risk profile of Taiwanese vegetarians. Eur J Clin Nutr. 2008;62(1):138-44. https://doi.org/10.1038/sj.ejcn.1602689 PMid:17356561 DOI: https://doi.org/10.1038/sj.ejcn.1602689

Unger CB, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, et al. International society of hypertension global hypertension practice guidelines. Hypertension 2020;75:1334-57. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.120.15026

Expert Panel on Detection E, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA. 2001;285(19):2486-97. https://doi.org/10.1001/jama.285.19.2486 PMid:11368702 DOI: https://doi.org/10.1001/jama.285.19.2486

Endocrinology ISo: Guidelines for the Management and Prevention of Type 2 Diabetes Mellitus in Adults in Indonesia. Indonesia: Indonesian Society of Endocrinology; 2019.

Beyrouti ME, Benjamin L, Cohen H, Farmer SF, Goh YY, Humphries F, et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry. 2020;91(8):889-91. https://doi.org/10.1136/jnnp-2020-323586 PMid:32354768 DOI: https://doi.org/10.1136/jnnp-2020-323586

Koupenova JE. Platelets and COVID-19: Inflammation, hyperactivation and additional questions. Circ Res. 2020;127(11):1419-21. https://doi.org/10.1161/CIRCRESAHA.120.318218 PMid:33151798 DOI: https://doi.org/10.1161/CIRCRESAHA.120.318218

Harris S, Rasyid A, Kurniawan M, Mesiano T, Hidayat R. Association of high blood homocysteine and risk of increased severity of ischemic stroke events. Int J Angiol. 2019;28(1):34-8. https://doi.org/10.1055/s-0038-1667141 PMid:30880891 DOI: https://doi.org/10.1055/s-0038-1667141

Guo YH, Chen FY, Wang GS, Chen L, Gao W. Diet-induced hyperhomocysteinemia exacerbates vascular reverse remodeling of balloon-injured arteries in rat. Chin Med J. 2008;121(22):2265-71. DOI: https://doi.org/10.1097/00029330-200811020-00011

Hofmann MA, Lalla E, Lu Y, Gleason MR, Wolf BM, Tanji N, et al. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest. 2001;107(6):675-83. https://doi.org/10.1172/JCI10588 PMid:11254667 DOI: https://doi.org/10.1172/JCI10588

Jakubowski H. Pathophysiological consequences of homocysteine excess. J Nutr. 2006;136(6 Suppl):1741S-9. PMid:16702349 DOI: https://doi.org/10.1093/jn/136.6.1741S

Deminice R, Silva TC, de Oliveira VH. Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis. World J Virol. 2015;4(2):147-55. https://doi.org/10.5501/wjv.v4.i2.147 PMid:25964880 DOI: https://doi.org/10.5501/wjv.v4.i2.147

Roblin X, Pofelski J, Zarski JP. Role of homocystine in course of hepatic stasis and chronic hepatitis C. Gastroentérol Clin Biol. 2007;31(4):415-20. DOI: https://doi.org/10.1016/S0399-8320(07)89402-4

Abike F, Engin AB, Dunder I, Tapisiz OL, Aslan C, Kutluay L. Human papilloma virus persistence and neopterin, folate and homocysteine levels in cervical dysplasias. Arch Gynecol Obstet. 2011;284(1):209-14. https://doi.org/10.1007/s00404-010-1650-7 PMid:20740364 DOI: https://doi.org/10.1007/s00404-010-1650-7

Zhong TX, Xu T, Peng Y, Wang A, Wang J, Peng H, et al. Plasma homocysteine and prognosis of acute ischemic stroke: A gender-specific analysis from CATIS randomized clinical trial. Mol Neurobiol. 2017;54(3):2022-30. https://doi.org/10.1007/s12035-016-9799-0 PMid:26910818 DOI: https://doi.org/10.1007/s12035-016-9799-0

Sadre-Marandi TD, Reed MC, Nijhout HF. Sex differences in hepatic one-carbon metabolism. BMC Syst Biol. 2018;12(1):89. https://doi.org/10.1186/s12918-018-0621-7 PMid:30355281 DOI: https://doi.org/10.1186/s12918-018-0621-7

Goyal NS, Jain R, Ram H. Do elevated levels of inflammatory biomarkers predict the risk of occurrence of ischemic stroke in SARS-CoV2? An observational study. J Stroke Cerebrovasc Dis. 2021;30(11):106063. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106063 PMid:34464929 DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106063

Lopez-Castaneda SG, Cano-Mendez A, Blancas-Ayala K, Damian-Vázquez G, Perez-Medina AI, Chora-Hernández LD, et al. Inflammatory and prothrombotic biomarkers associated with the severity of COVID-19 infection. Clin Appl Thromb Hemost. 2021;27:1076029621999099. https://doi.org/10.1177/1076029621999099 PMid:33835872 DOI: https://doi.org/10.1177/1076029621999099

Sarengat R, Islam MS, Ardhi MS. Correlation of neutrophil-to-lymphocyte ratio and clinical outcome of acute thrombotic stroke in patients with COVID-19. Narra J. 2021;1(3):50. https://doi.org/10.52225/narra.v1i3.50 DOI: https://doi.org/10.52225/narra.v1i3.50

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Published

2022-02-21

How to Cite

1.
Syahrul S, Imran I, Musadir N, Mutiawati VK. Severe Acute Respiratory Syndrome Coronavirus 2 Infection is Associated with Homocysteine Level and Clinical Outcomes in Ischemic Stroke Patients. Open Access Maced J Med Sci [Internet]. 2022 Feb. 21 [cited 2024 Nov. 22];10(B):554-8. Available from: https://oamjms.eu/index.php/mjms/article/view/8243

Funding data

  • Universitas Syiah Kuala
    Grant numbers Calon Profesor Research Scheme Financial Year 2021 (167/UN11/ SPK/PNBP/2021).