ANALYSIS OF RISK FACTORS FOR NEUROLOGICAL COMPLICATIONS OF SARS-COV-2 INFECTION: FOCUS ON CHRONIC FATIGABILITY
DOI:
https://doi.org/10.22551/MSJ.2025.04.03Abstract
Aim: Chronic fatigue syndrome is a long-term neurological manifestation that significantly affects the quality of life of patients. Its etiology is incompletely known, although it can occur after various infections including COVID-19, and the associated risk factors are not fully defined. The aim of the current study was to evaluate neurological manifestations in long-COVID and to identify potential risk factors for these complications. Materials and methods: We performed retro - prospective study on patients with history of COVID-19 infections. Patients were assessed up to 3 years after infection. Clinical and neurological investigations, brain imaging, analysis of inflammatory markers, levels of vitamin B12, folic acid and vitamin D were carried out. Neurocognitive status was assessed using a validated semiquantitative scale. Results: In 132 eligible patients, 41.67% of cases developed chronic fatigability. Other neurological manifestations associated with Long-COVID were dizziness (29.17% cases), and memory impairment (25% cases). The deterioration of the neurocognitive status 1 year after infection was significantly correlated with the patient’s age (p<0,0001), serum vitamin D (p=0.015), as well as vitamin B12 (p=0.006). Conclusions: Chronic fatigability is a common neurological complication of COVID-19 infection. Older people, those with low vitamin D and vitamin B12 levels, have higher risk of developing this syndrome. The COVID-19 infected patients need multiple investigations and a multidisciplinary approach to prevent these long-term complications.
References
1. Struhal W, Almamoori D. A review of the sequelae of post COVID-19 with neurological implications (post-viral syndrome). J Neurol Sci 2025; 474: 123532.
2. Department of Health and Human Services, Office of the Assistant Secretary for Health. National Research Action Plan on Long COVID, 2022. Available from https://www.covid.gov/assets/ files/ National-Research-Action-Plan-on-Long-COVID-08 012022.pdf.
3. Soriano JB, Murthy S, Marshall JC, et al. WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 2022; 22(4): e102-e107.
4. Desai AD, Lavelle M, Boursiquot BC, et al. Long-term complications of COVID-19. Am J Physiol Cell Physiol 2022; 322(1): C1-C11.
5. Talkington GM, Kolluru P, Gressett TE, et al. Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics. Front Neurol 2025; 15: 1465787.
6. Hou Y, Gu T, Ni Z, et al. Global Prevalence of Long COVID, its Subtypes and Risk factors: An Updated Systematic Review and Meta-Analysis. medRxiv [Preprint]. 2025; 6: 2025.01.01.2431 9384.
7. Diaconu IE, Irimie-Băluță RE, Vâţa A et al. COVID-19 neurological manifestations - the experience of a tertiary hospital from northeastern Romania. Med Surg J-Rev Med Chir Soc Med Nat Iasi 2024; 128(1): 21-33.
8. Duong KE, Lu JY, Wang S, et al. Incidence and risk factors of new clinical disorders in patients with COVID-19 hyperinflammatory syndrome. Sci Rep 2025;15(1): 19892.
9. Dubey S, Das S, Ghosh R, Dubey MJ, et al. The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia. J Alzheimers Dis Rep 2023; 7(1): 119-128.
10. 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.
11. Xu E, Xie Y, Al-Aly Z. Long-term neurologic outcomes of COVID-19. Nat Med 2022; 28(11): 2406-2415.
12. Rivera MC, Mastronardi C, Silva-Aldana CT, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: a comprehensive review. Diagnostics (Basel) 2019; 9(3): 91.
13. Bested AC, Marshall LM. Review of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians. Rev Environ Health 2015; 30(4): 223-249.
14. Palacios N, Molsberry S, Fitzgerald KC, et al. Different risk factors distinguish myalgic enceph-alomyelitis/chronic fatigue syndrome from severe fatigue. Sci Rep 2023;13(1):2469.
15. Taha R, Abureesh S, Alghamdi S, et al. The Relationship Between Vitamin D and Infections Including COVID-19: Any Hopes? Int J Gen Med 2021; 14: 3849-3870.
16. Hill A, Starchl C, Dresen E, et al. An update of the effects of vitamins D and C in critical illness. Front Med (Lausanne) 2023; 9: 1083760.
17. Vâţă A, Roşu FM, Dorneanu OS, et al. Antibiotic Usage in the COVID-19 Intensive Care Unit of an Infectious Diseases Hospital from Nord-Eastern Romania. Medicina 2023; 59: 645 / doi: 10.3390/medicina59040645,
18. Mayne PE, Burne THJ. Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness. Trends Neurosci 2019; 42(4): 293-306.
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