Higher Inflammatory Markers are correlated with Worse Cognitive Function in Coronavirus Disease-2019 Patients


  • Fasihah Irfani Fitri Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital Medan Indonesia, Medan, Indonesia https://orcid.org/0000-0002-0883-3029
  • Winda Rahmah Darman Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital Medan Indonesia, Medan, Indonesia
  • Kiking Ritarwan Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Adam Malik General Hospital Medan Indonesia, Medan, Indonesia




COVID-19, C-reactive protein, Cognitive, D-Dimer, Ferritin, Inflammation


AIM: This study aimed to determine the correlation between inflammation with cognitive function in COVID-19 patients.

METHODS: We recruited COVID-19 patients using consecutive sampling methods in Adam Malik General Hospital Medan, Indonesia. The neutrophil-to-lymphocyte ratio (NLR,) C-reactive protein (CRP), D-dimer, and ferritin serum levels were measured as inflammatory markers . Cognitive function was assessed in several cognitive domains using Forward Digit Span for attention, Bacward Digit Span for working memory, and Trail Making Test parts A and B for executive function. The correlation between inflammatory markers and cognitive function was analyzed using Spearman correlation test.

RESULTS: This study involved 40 COVID-19 patients consisting of 13 (32.5%) males and 27 (67.5%) females; the median age of the patients was 39.5 (19–65) years. We found that higher D-dimer and ferritin levels were significantly correlated with worse BDS scores (r = −0.369 p = 0.019 and r = −0.408 p = 0.009, respectively) and higher ferritin level was also correlated with worse FDS score (r = −0.365 p = 0.020 and). Higher D-dimer and ferritin levels were also significantly correlated with a longer time of completion of TMT-B (r = 0.363 p = 0.022 and r = 0.433 p = 0.005) and higher ferritin level was also correlated with a longer time of completion of TMT-A (r = 0.438 P=0.005). There were no significant correlations between NLR and CRP levels with cognitive function.

CONCLUSION: Higher inflammatory markers are correlated with worse attention, working memory, and executive function in COVID-19 patients.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Li Z, Liu T, Yang N, Han D, Mi X, Li Y, et al. Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the pheriphery to the brain. Front Med. 2020;14(5):533-41. https://doi.org/10.1007/s11684-020-0786-5 PMid:32367431 DOI: https://doi.org/10.1007/s11684-020-0786-5

Situasi Terkini Perkembangan Coronaviru Disease (COVID-19); 2021. Available from: https://infeksiemerging.kemkes.go.id. [Last accessed on 2022 Jan 21].

Wildwing T, Holt N. The neurological symptoms of COVID-19: A systematic overview of systematic reviews, comparison with other neurological conditions and implications for healthcare services. Ther Adv Chronic Dis. 2021;12:76979. https://doi.org/10.1177/2040622320976979 PMid:33796241 DOI: https://doi.org/10.1177/2040622320976979

Ermis U, Rust MI, Bungenberg J, Costa A, Dreher M, Balfanz P, et al. Neurological symptoms in COVID-19: A cross-sectional monocentric study of hospitalized patients. Neurol Res Pract. 2021;3(1):17. https://doi.org/10.1186/s42466-021-00116-1 PMid:33712089 DOI: https://doi.org/10.1186/s42466-021-00116-1

Vyas A, Panwar VR, Mathur V, Patel P, Mathur S, Sharma A, et al. Mild cognitive impairment in COVID-19 survivors: Measuring the brain fog. Int J Ment Health. 2021 ;20:1-12. DOI: https://doi.org/10.1080/00207411.2021.1988402

Garcia-Grimshaw M, Chirino-Perez A, Flores-Silva FD, Valdes- Ferrer SI, Vargas-Martinez MD, Jimenez-Avila AI, et al. Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: A multivariate causality model analysis. Neurol Sci. 2021:43(2):2217-29. https://doi.org/10.1007/s10072-021-05798-8 PMid:35022935 DOI: https://doi.org/10.1007/s10072-021-05798-8

Susilawathi NM, Tini K, Wijayanti IA, Rahmawati PL, Wardhana DP, Samatra DP, et al. Neurological manifestations of CVID-19: A clinical approach. Med J Indonesia. 2021;30(2):157-65. DOI: https://doi.org/10.13181/mji.rev.204821

Gustine JN, Jones D. Immunopathology of hyperinflammation in COVID-19. Am J Pathol. 2021;191(1):4-17. https://doi.org/10.1016/j.ajpath.2020.08.009 PMid:32919977 DOI: https://doi.org/10.1016/j.ajpath.2020.08.009

Ren AL, Digby RJ, Needham EJ. Neurological update: COVID-19. J Neurol. 2021;268:4379-87. https://doi.org/10.1007/s00415-021-10581-y PMid:33929617 DOI: https://doi.org/10.1007/s00415-021-10581-y

Nalbant A, Kaya T, Varim C, Yaylaci S, Tamer A, Cinemre H. Can the neutrophil/lymphocyte ratio (NLR) have a role in the diagnosis of coronavirus 2019 disease (COVID-19)? Rev Assoc Med Bras. 2020;66(6):746-51. https://doi.org/10.1590/1806-9282.66.6.746 PMid:32696861 DOI: https://doi.org/10.1590/1806-9282.66.6.746

Huang I, Pranata R, Lim MA, Oehadian A, Alisjahbana B. C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: A meta-analysis. Ther Adv Respir Dis. 2020;14:1-14. https://doi.org/10.1177/1753466620937175 PMid:32615866 DOI: https://doi.org/10.1177/1753466620937175

Miskowiak KW, Johnsen S, Sattler SM, Nielsen S, Kunalan K, Rungby J. et al. Cognitive impairments four months after COVID-19 hospital discharge: Pattern, severity and association with illness variables. Eur Neuropsychopharmacol. 2021;46:39-48. https://doi.org/10.1016/j.euroneuro.2021.03.019 PMid:33823427 DOI: https://doi.org/10.1016/j.euroneuro.2021.03.019

Putzu I, Robert CD. White blood cells identification and counting from microscopic blood image. World Acad Sci Eng Technol. 2013;73:363-70.

Sproston NR, Asworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol. 2018;9:754. https://doi.org/10.3389/fimmu.2018.00754 PMid:29706967 DOI: https://doi.org/10.3389/fimmu.2018.00754

Natalya MA, Diana VK, Shima M, Saenkoa EL. Intrinsic pathway of blood coagulation contributes to thrombogenicity of atherosclerotic plaque. Blood. 2002;99(12):4475-85. https://doi.org/10.1182/blood-2001-11-0140 PMid:12036878 DOI: https://doi.org/10.1182/blood-2001-11-0140

Fei F, Smith JA, Cao L. Clinical laboratory characteristics in patients with suspected COVID-19: One single-institution experience. J Med Virol. 2020;93(3):1665-71. https://doi.org/10.1002/jmv.26527 PMid:32946118 DOI: https://doi.org/10.1002/jmv.26527

Cao P, Wu Y, Wu S, Wu T, Zhang Q, Zhang R, et al. Elevated serum ferritin level effectively discriminates severity illness and predicts prognosis of COVID-19 patients. Res Sq. 2020 ;26:1-12. DOI: https://doi.org/10.21203/rs.3.rs-31914/v1

Tombaugh NT. Trail making test A and B: Normative data stratified by age and education. Arch Clin Neuropsychol. 2004;19:203-14. DOI: https://doi.org/10.1016/S0887-6177(03)00039-8

Centers for Disease Control and Prevention; 2021. Available from: https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm. [Last accessed on 2021 Nov 25].

Li, Y, Wang C, Peng M. Aging immune system and its correlation with liability to severe lung complications. Front Public Health. 2021;9: 735151. https://doi.org/10.3389/fpubh.2021.735151 PMid:34888279 DOI: https://doi.org/10.3389/fpubh.2021.735151

Biswas M, Rahaman S, Biswas TK, Haque Z, Ibrahim B. Association of sex, age, and comorbidities with mortality in COVID-19 patients: A systematic review and meta-analysis. Intervirology. 2021;64:36-47. https://doi.org/10.1159/000512592 PMid:33296901 DOI: https://doi.org/10.1159/000512592

Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimers Res Ther. 2020;12(1):69. https://doi.org/10.1186/s13195-020-00640-3 PMid:32498691 DOI: https://doi.org/10.1186/s13195-020-00640-3

Pranata H, Batubara CA, dan Sinurat PP. Hubungan rasio neutrofil dan high sensitivity C-reactive protein dengan Keparahan dan outcome pada Psien Stroke Iskemik Akut. [Tesis]. Medan: Universitas Sumatera Utara, Program Magister (S-2) Ilmu Kedokteran; 2020.

Qeadan F, Tingey B, Gu LY, Packard AH, Erdei E, Saeed AI. Prognostic values of serum ferritin and D-dimer trajectory in patients with COVID-19. Viruses. 2021;13(3):491. https://doi.org/10.3390/v13030419 PMid:33807920 DOI: https://doi.org/10.3390/v13030419

Aykut DS, Arslan FC, Karaguzel EO, Aral G, Karakullukcu S. The relationship between neutrophil-lymphocyte, platelet-lymphocyte ratio and cognitive function in bipolar disorder. Nord J Psychiatry. 2018;72(2):119-23. https://doi.org/10.1080/08039 488.2017.1397192 PMid:29108448 DOI: https://doi.org/10.1080/08039488.2017.1397192

Renteria MA, Gillet SR, McCLure LA, Wadley VG, Glasser SP, Howard VJ, et al. C-reactive protein and risk of cognitive decline: The REGARDS study. PLoS One. 2020;15(12):e0244612. https://doi.org/10.1371/journal.pone.0244612 PMid:33382815 DOI: https://doi.org/10.1371/journal.pone.0244612

Frontera JA, Boutajangout A, Masurkar AV, Betensky RA, Ge Y, Vedvyas A, et al. Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer’s dementia. Alzheimers Dement. 2022 ;18:12556. https://doi.org/10.1002/alz.12556 PMid:35023610 DOI: https://doi.org/10.1002/alz.12556

Turana T, Nathaniel M, Shen R, Ali S, Aparasu RR. Citicoline and COVID-19-related cognitive and other neurologic complications. Brain Sci. 2022;12(1):59. https://doi.org/10.3390/brainsci12010059 PMid:35053804 DOI: https://doi.org/10.3390/brainsci12010059

Xu J, Sun W, and Yang L. Association between iron metabolism and cognitive impairment in older non-alcoholic fatty liver disease individuals: A cross-sectional study in patients from a Chinese center. Medicine (Baltimore). 2019;98(48):e18189. https://doi.org/10.1097/MD.0000000000018189 PMid:31770275 DOI: https://doi.org/10.1097/MD.0000000000018189

Sfera A, Osorio C, Maguire G, Rahman L, Afzaal J, Cummings M, et al. COVID-19, ferrosenescence and neurodegeneration, a mini-review. Prog Neuropsychopharmacol Biol Psychiatry. 2021;109:110230. https://doi.org/10.1016/j.pnpbp.2020.110230 PMid:33373681 DOI: https://doi.org/10.1016/j.pnpbp.2020.110230

Pyne JD, Brickman AM. The impact of the COVID-19 pandemic on dementia risk: Potential pathways to cognitive decline. Neurodegener Dis. 2021;21(1-2):1-23. https://doi.org/10.1159/000518581 PMid:34348321 DOI: https://doi.org/10.1159/000518581




How to Cite

Fitri FI, Darman WR, Ritarwan K. Higher Inflammatory Markers are correlated with Worse Cognitive Function in Coronavirus Disease-2019 Patients. Open Access Maced J Med Sci [Internet]. 2022 Apr. 22 [cited 2024 Apr. 21];10(B):1206-11. Available from: https://oamjms.eu/index.php/mjms/article/view/9472

Most read articles by the same author(s)

1 2 > >>