Cerebrospinal Fluid Analysis in Patients with COVID-Induced Encephalopathy

Document Type : Original Article

Authors

1 Department of Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Department of Neurosurgery, Isfahan University of Medical Sciences, Isfahan, Iran

3 Isfahan University of Medical Sciences, Isfahan, Iran

Abstract
Background: The novel coronavirus has been found to have neurological manifestations, and cerebrospinal fluid (CSF) analysis could be helpful in the differential diagnosis of critically ill patients with neurological symptoms and act as a prognostic factor in these patients.
Objectives: In this study, we assessed the CSF of patients with COVID-19 who presented with encephalopathy to elucidate any common characteristics.
Methods: This cross-sectional study included 36 patients with positive COVID-19 PCR who presented with encephalopathy and were hospitalized. We evaluated RT-PCR, total cell counts, LDH, protein, and glucose levels of CSF samples. Clinical manifestations, neurological complaints, and outcomes (death or survival) were extracted from patients' files.
Results: A total of 36 patients underwent lumbar puncture and CSF analysis. RT-PCR for SARS-CoV-2 RNA was negative in all thirty-six cases. Fever was present in 29 (80.6%) patients, shortness of breath in 23 (63.9%), and cough in 14 (38.9%) as primary clinical manifestations. Seizures were reported in 12 (33.3%) patients as a neurological presentation. The mortality rate was 7 (19.4%) in our cases. Abnormalities in WBC count were found in 6 (16.6%) of CSF samples. The remaining patients had normal CSF results, indicating no specific pattern of CSF markers.
Conclusion: Our study did not reveal any usual patterns in CSF analysis. Moreover, we were unable to detect SARS-CoV-2 RNA in CSF samples definitively. These findings suggest that the indirect mechanisms of SARS-CoV-2 may play a significant role in the neurological manifestations associated with COVID-19.

Keywords


  1. Zhou H, Jin M, Ma Q. Remedy for work stress: the impact and mechanism of ethical leadership. Cent Eur J Public Heal. 2015;23(2):176.
  2. Toklu H, Ganti L, Crimi E, Cintron C, Hagan J, Serrano E. Cerebrospinal fluid findings and hypernatremia in COVID-19 patients with altered mental status. Int J Emerg Med. 2020;13:63. doi:10.1186/s12245-020-00327-4
  3. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/ encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020;94:55-8. doi:10.1016/j.ijid.2020.03.062
  4. Tandon M, Kataria S, Patel J, Mehta TR, Daimee M, Patel V, et al. A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19. Int J Infect Dis. 2021;104:390-7. doi:10.1016/j.ijid.2021.01.002
  5. Hrishi AP, Sethuraman M. Cerebrospinal fluid (CSF) analysis and interpretation in neurocritical care for acute neurological conditions. Indian J Crit Care Med. 2019;23(Suppl 2):S115-9. doi:5005/jp-journals-10071-23187
  6. Dando SJ, Mackay-Sim A, Norton R, Currie BJ, John JAS, Ekberg JAK, et al. Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion. Clin Microbiol Rev. 2014;27(4):691-726. doi:10.1128/cmr. 00118-13
  7. Tsivgoulis G, Palaiodimou L, Zand R, Lioutas VA, Krogias C, Katsanos AH, et al. COVID-19 and cerebrovascular diseases: a comprehensive overview. Ther Adv Neurol Disord. 2020;13:1756286420978 004. doi:10.1177/1756286420978004
  8. Chu H, Chan JF-W, Yuen TT-T, Shuai H, Yuan S, Wang Y, et al. Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Lancet Microbe. 2020;1(1):e14–23. doi:10.1016/S2666-524 7(20)30004-5
  9. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382(23): 2268-70. doi:10.1056/NEJMc2008597
  10. Destras G, Bal A, Escuret V, Morfin F, Lina B, Josset L. Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic. Lancet Microbe. 2020;1(4):e149. doi:10.1016/S2666-5247(20)30066-5
  11. Neumann B, Schmidbauer ML, Dimitriadis K, Otto S, Knier B, Niesen WD, et al. Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms. J Neurol Sci. 2020;418:117090. doi:1016/j.jns.2020.117090
  12. Bellon M, Schweblin C, Lambeng N, Cherpillod P, Vazquez J, Lalive PH, Schibler M, Deffert C. Cerebrospinal fluid features in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) positive patients. Clin Infect Dis. 2021;73(9):e3102-5. doi:10.1093/cid/ciaa1165
  13. de Melo Espndola O, Siqueira M, Soares CN, de Lima MA, Leite AC, Araujo AQ, et al. Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid. Int J Infect Dis. 2020;96:567-9. doi:10.1016/j.ijid.2020.05.123
  14. Kamal YM, Abdelmajid Y, Al Madani AA. Cerebrospinal fluid confirmed COVID-19-associated encephalitis treated successfully. BMJ Case Rep. 2020;13:e237378. doi:10.1136/bcr-2020-237378
  15. Tuma RL, Guedes BF, Carra R, Iepsen B, Rodrigues J, Camelo-Filho AE, et al. Clinical, cerebrospinal fluid, and neuroimaging findings in COVID-19 encephalopathy: a case series. Neurol Sci. 2021;42: 479-89. doi:10.1007/s10072-020-04946-w
  16. Moghimi M, Moghtader A, Jozpanahi M, Khodadadi K, Jafarzade M, Abbaspour Z. Correlation between CSF biomarkers and COVID-19 meningoencephalitis: A case series. Respir Med Case Rep. 2020;32:101335. doi:10.1016/j.rmcr.2020.101335
  17. Garg RK, Paliwal VK, Gupta A. Encephalopathy in patients with COVID‐19: a review. J Med Virol. 2021; 93(1):206-22. doi:10.1002/jmv.26207
  18. Lucchese G. Cerebrospinal fluid findings in COVID-19 indicate autoimmunity. Lancet Microbe. 2020;1(6): e242. doi:10.1016/S2666-5247(20)30147