Long-COVID neurological symptoms are associated with D-dimer levels in COVID-19 patients
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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.
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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.