Main Article Content
Coronavirus disease 2019 (COVID-19) is a disease designated as a global pandemic by the WHO that can manifest clinically as neurological disorders that can occur in the acute phase or after the acute phase (long COVID-19), such as headache, myalgia, anosmia, and cognitive impairment. These neurological disorders as symptoms of long COVID-19 are presumably caused by hypercoagulable conditions characterized by an increase in D-dimer level. This study aims to determine the correlation of long COVID-19 neurological symptoms with hypercoagulable conditions and the role of D-dimer as a biomarker of long COVID-19 neurological symptoms.
This was a cross-sectional study involving 31 patients with long COVID-19 symptoms. Admitted long COVID-19 cases with recorded D-dimer levels and definitive outcomes were included consecutively. Long COVID-19 neurological symptoms were collected. D-dimer level was measured using immunofluorescence assay and reported in fibrinogen equivalent units (ìg/mL). The correlation between D-dimer levels and neurological clinical manifestations was assessed by using ordinal regression analysis. The p-value of <0.05 was considered statistically significant.
The mean age of the subjects was 38.81 ± 11.58 years and 18 (58.06%) were female. Long COVID neurological symptoms comprised myalgia, anosmia and cephalgia, and most subjects complained of myalgia (80.65%). On multivariable analysis, long-COVID-19 neurological symptoms were significantly correlated with D-dimer [odds ratio (OR) = 1.05; p=0.020].
The number of neurological long COVID symptoms were significantly correlated with level of D-Dimer. Ultimately, more clarity is needed on the neurological impact of COVID-19, its diagnosis, and its treatment.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.
World Health Organization. Coronavirus cases. Geneva: World Health Organization;2021.
Kementerian Kesehatan Republik Indonesia. Coronavirus. Jakarta: Kementerian Kesehatan Republik Indonesia;2021.
Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 2020;46:586–90. doi: 10.1007/s00134-020-05985-9.
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020; 94:e00127-20. doi: 10.1128/JVI.00127-20.
Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683–90. doi:10.1001/jamaneurol.2020.1127.
Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 2020;92 :552–5. doi: 10.1002/jmv.25728.
Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020;382: 2268–70. doi: 10.1056/NEJMc2008597.
Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host–virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci 2020;11:995–8. doi: 10.1021/acschemneuro.0c00122.
Stefanou Ml, Palaiodimou L, Bakola E, et al. Neurological manifestations of long-COVID syndrome: a narrative review. Ther Adv Chronic Dis 2022;13:20406223221076890. doi: 10.1177/20406223221076890.
Jesuthasan A, Massey F, Manji H, Zandi MS, Wiethoff S. Emerging potential mechanisms and predispositions to the neurological manifestations of COVID-19. J Neurol Sci 2021;428:117608. doi: 10.1016/j.jns.2021.117608.
Akbarialiabad H, Taghrir MH, Abdollahi A, et al. Long COVID, a comprehensive systematic scoping review. Infection 2021;49:1163–86. doi: 10.1007/s15010-021-01666-x.
Garg M, Maralakunte M, Garg S, et al. The conundrum of ‘long-covid-19ʹ: narrative review. Int J Gen Med 2021;14:2491–506. doi: 10.2147/IJGM.S316708.
Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond) 2021;53:737-54. doi: 10.1080/23744235.2021.192439.
Ortega-Paz L, Capodanno D, Montalescot G, Angiolillo DJ. Coronavirus disease 2019–associated thrombosis and coagulopathy: review of the pathophysiological characteristics and implications for antithrombotic management. J Am Heart Assoc 2021;10:1–24. https://doi.org/10.1161/JAHA.120.019650.
Townsend L, Fogarty H, Dyer A, et al. Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response. J Thromb Haemost 2021;19:1064–70. doi: 10.1111/jth.15267.
Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020;135:2033-40. doi: 10.1182/blood.2020006000.
Iser BPM, Sliva I, Raymundo VT, Poleto MB, Schuelter-Trevisol F, Bobinski F. Suspected COVID-19 case definition: a narrative review of the most frequent signs and symptoms among confirmed cases. Epidemiol Serv Saude 2020;29:e2019354. doi: 10.5123/S1679-49742020000300018.
Lechien JR, Barillari MB, Jouffe L, Saussez S. Anosmia is a key symptom of COVID-19 infection and should be used as a diagnostic tool. Ear Nose Throat J 2020;99:577-8. doi: 10.1177/0145561320925191.
Yao Y, Cao J, Wang Q, et al. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study. J Intensive Care 2020;8:49. https://doi.org/10.1186/s40560-020-00466-z.
Poudel A, Poudel Y, Adhikari A, et al. D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19. PLoS ONE 2021;16:e0256744. https://doi.org/10.1371/journal.pone.0256744.
Camargo-Martínez W, Lozada-Martínez I, Escobar-Collazos A, et al. Post-COVID 19 neurological syndrome: implications for sequelae's treatment. J Clin Neurosci 2021;88:219-25. doi: 10.1016/j.jocn.2021.04.001.
Osawa I, Okamoto K, Ikeda M, Otani A, Wakimoto Y, Yamashita T. Dynamic changes in fibrinogen and D-dimer levels in COVID-19 patients on nafamostat mesylate. J Thromb Thrombolysis 2021;51:649–56. doi: 10.1007/s11239-020-02275-5.
Simadibrata DM, Lubis AM. D-dimer levels on admission and all-cause mortality risk in COVID-19 patients: a meta-analysis. Epidemiol Infect 2020;148:e202. doi: 10.1017/S0950268820002022.
Favaloro EJ, Thachil J. Reporting of D-dimer data in COVID-19: some confusion and potential for misinformation. Clin Chem Lab Med 2020;58:1191–9. doi: 10.1515/cclm-2020-0573.