COVID-19-associated meningitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Wajeeha Aiman, M.D.[2], Muhammad Adnan Haider, M.B.B.S.[3] Tayebah Chaudhry[4] Syed Musadiq Ali M.B.B.S.[5]


Overview

Covid-19 associated meningitis was first discovered by Moriguchi T. et al. a Japanese critical care physician in late February 2020 during the pandemic of SARS-CoV-2. Duong L et. reported a case of a young female with COVID-19 who developed meningoencephalitis without respiratory failure in Downtown Los Angeles in early April, 2020. Bernard-Valnet R et al. reported two cases of meningoencephalitis in patients with concomitant SARS-CoV-2 infection. There is no established system for the classification of SARS-CoV-2 related meningitis. There are three mechanisms proposed for pathophysiology of COVID-19-associated meningitis. SARS-CoV-2 directly reaches brain through cribriform plate which is located in close proximity to olfactory bulb. This is supported by the facts that some patients of COVID-19 present with anosmia and hyposmia. Viral interaction with ACE2 expressed on neurons lead to damage to neurons and inflamation (encephalitis) and inflammation of brain membranes (meningitis). SARS-CoV-2 can reach brain via anterograde or retrograde transport with the help of motor proteins kinesin and dynein via sensory nerve endings, especially afferent nerve endings of vagus nerve from lungs.

Historical Perspective

  • Neurological symptoms in COVID-19 patients were first reported in February 2020 in a retrospective case series study by Mao L. et al. in hospitalized COVID-19 patients in Wuhan.
  • Ling Mao from Tongji Medical College in Wuhan, and his group reviewed the data retrospectively from January 16, 2020, to February 19, 2020.
  • One third of the 214 hospitalized laboratory- confirmed COVID-19 patients included in this study reported at least one neurological symptom.
  • Covid-19 associated meningitis was first discovered by Moriguchi T. et al. a Japanese critical care physician in late February 2020 during the pandemic of SARS-Coronavirus-2: SARS-CoV-2 [1].
  • Duong L et. reported a case of a young female with COVID-19 who developed meningoencephalitis without respiratory failure in Downtown Los Angeles in early April, 2020 [2].
  • Bernard-Valnet R et al. reported two cases of meningoencephalitis in patients with concomitant SARS-CoV-2 infection.[3]

Classification

  • There is no established system for the classification of COVID-19-associated meningitis.

Pathophysiology

The exact pathogenesis of COVID-19-associated meningitis is not fully understood.

The proposed pathophysiology of COVID-19-associated meningitis is by following three mechanisms;

1.Direct pathway

2. Blood circulation pathway

3. Neuronal Pathway

Meningitis Pathophysiology.png


Causes

Differentiating COVID-19-associated meningitis from other Diseases

  • For further information about the differential diagnosis, click here.
  • To view the differential diagnosis of COVID-19, click here.

Epidemiology and Demographics

Risk Factors

Screening

  • There is insufficient evidence to recommend routine screening for COVID-19-associated meningitis.
  • To view screening for COVID-19, click here.

Natural History, Complications, and Prognosis

History

  • If left untreated, COVID-19-associated meningitis may cause long term neurological complications.
  • To view Natural History for COVID-19, click here.

Complications

If left untreated, meningitis in COVID-19 patients may develop following complications.

Prognosis

  • Exact prognosis of COVID-19 associated meningitis is not known.
  • However, treating the underlying cause i.e., COVID-19, including treatment with steroids, have shown improvement in meningitis symptoms in a COVID-19 patient.
  • To view Prognosis for COVID-19, click here.

Diagnosis

Diagnostic Study of Choice

  • The diagnostic study of choice for meningitis in COVID-19 patients is CSF analysis and ruling out other causes of meningitis (e.g., other viruses, bacteria, fungi).

History and Symptoms

History

  • The disease course of 5 cases of COVID-19 associated meningitis include:
Patient No. Early symptoms Late symptoms CSF analysis Viral panel (HSV,VZV, enterovirus) Bacterial panel SARS-CoV-2 analysis Imaging CT/MRI
Protein(mg/L) Glucose(CSF:serum ratio) Cells (mm3) RT-PCR CSF RT-PCR Nasopharyngeal swab
  1. 24 year old male, presented with meningitis in Japan[16]
Headache,

Fever,

fatigue

Worsening headache, Sore throat. (Day 5)

Impaired consciousness and transient generalized seizure, (Day 9)

NA NA Cell count was 12/μL–10

mononuclear and 2 polymorphonuclear cells

Negative Positive Negative Brain MRI:

Hyperintensity in the right lateral ventricle's inferior horn along the wall,

pan-paranasal sinusitis.

2. 64 year old female with a known contact with SARS-CoV-2 (her husband tested positive 15 days before)[17] Mild flue like symptoms

myalgia

cough

Tonic-clonic seizures

disorientation

psychotic symptoms

466 mg/L 0.59 17 cells with 97% lymphocytes negative negative positive Brain MRI normal at admission
3. 67 year old female with known SARS-CoV-2 for 17 days with mild respiratory symptoms[18] wake up severe headache Drowsiness, disoriented was lying on the floor, brought to hospital with confusion, disorientation, 461

mg/L

0.62 21 cells with 87 % cells were lymphocytes negative negative positive Brain MRI normal at admission
4. 69 year old man who returned from Middle East 15 days ago (French Indies)[19] 7 day history of

fever

cough

myalgia

cervical pain

ageusia

anosmia

Severe headache

neck stiffness

confusion

84

mg/L

normal 37 cells, purely lymphocytes, with no RBCs negative neagtive negative on nasopharyngeal swab but became positive on bronchoalveolar lavage on 4th day of admission Brain MRI normal on admission
5. 41 year old female, presented with meningoencephalitis without respiratory failure in Downtown Los Angeles in April 2020[20] fever

headache

new onset seizure

severe headache

neck stiffness

photophobia

100

mg/L

0.60 70 cells with 100% lymphocytes negative NA positive CT head without contrast was normal

Common Symptoms

Less Common Symptoms

Physical Examination

Vitals:

Neuromuscular:

Laboratory Findings

Cerebrospinal fluid level Normal level Bacterial meningitis[26] SARS-CoV-2 meningitis Viral meningitis[26] Fungal meningitis Tuberculous meningitis[28] Malignant meningitis[23]
Cells/ul < 5 >300 10-1000 10-1000 10-500 50-500 >4
Cells Lymphos:Monos 7:3 Gran. > Lymph predominantly lymphocytes Lymph. > Gran. Lympho.>Gran Lymphocytes Lymphocytes
Total protein (mg/dl) 45-60 Typically 100-500 Normal or slightly high Normal or slightly high High Typically 100-200 >50
Glucose ratio (CSF/plasma)[24] > 0.5 < 0.3 > 0.6 > 0.6 <0.3 < 0.5 <0.5
Lactate (mmols/l)[25] < 2.1 > 2.1 N/A < 2.1 >3.2 > 2.1 >2.1
Others ICP:6-12 (cm H2O) CSF gram stain, CSF culture, CSF bacterial antigen RT-PCR for SARS-CoV-2 RNA in CSF (still not approved by FDA) PCR of HSV-DNA, VZV CSF gram stain, CSF india ink PCR of TBC-DNA CSF tumour markers such as alpha fetoproteins, CEA

Electrocardiogram

X-ray

  • There are no x-ray findings associated with COVID-19-associated meningitis.
  • To view the x-ray finidings on COVID-19, click here.

Echocardiography or Ultrasound

CT scan

MRI

Other Imaging Findings

  • There are no other imaging findings associated with COVID-19 associated meningitis.

Other Diagnostic Studies

  • There are no other diagnostic studies associated with COVID-19 associated meningitis.

Treatment

Medical Therapy

The mainstays of medical therapy for viral meningitis are:[29][30][31][32][33][34][35]

Symptomatic treatments:

Surgery

Primary Prevention

Secondary Prevention

References

  1. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J; et al. (2020). "A first case of meningitis/encephalitis associated with SARS-Coronavirus-2". Int J Infect Dis. 94: 55–58. doi:10.1016/j.ijid.2020.03.062. PMC 7195378 Check |pmc= value (help). PMID 32251791 Check |pmid= value (help).
  2. Duong L, Xu P, Liu A (2020). "Meningoencephalitis without respiratory failure in a young female patient with COVID-19 infection in Downtown Los Angeles, early April 2020". Brain Behav Immun. 87: 33. doi:10.1016/j.bbi.2020.04.024. PMC 7162766 Check |pmc= value (help). PMID 32305574 Check |pmid= value (help).
  3. Bernard-Valnet R, Pizzarotti B, Anichini A, Demars Y, Russo E, Schmidhauser M; et al. (2020). "Two patients with acute meningoencephalitis concomitant with SARS-CoV-2 infection". Eur J Neurol. doi:10.1111/ene.14298. PMC 7267660 Check |pmc= value (help). PMID 32383343 Check |pmid= value (help).
  4. Tsai LK, Hsieh ST, Chang YC (2005). "Neurological manifestations in severe acute respiratory syndrome". Acta Neurol Taiwan. 14 (3): 113–9. PMID 16252612.
  5. Schoeman D, Fielding BC (2019). "Coronavirus envelope protein: current knowledge". Virol J. 16 (1): 69. doi:10.1186/s12985-019-1182-0. PMC 6537279 Check |pmc= value (help). PMID 31133031.
  6. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H; et al. (2020). "Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding". Lancet. 395 (10224): 565–574. doi:10.1016/S0140-6736(20)30251-8. PMC 7159086 Check |pmc= value (help). PMID 32007145 Check |pmid= value (help).
  7. Baig AM, Khaleeq A, Ali U, Syeda H (2020). "Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms". ACS Chem Neurosci. 11 (7): 995–998. doi:10.1021/acschemneuro.0c00122. PMC 7094171 Check |pmc= value (help). PMID 32167747 Check |pmid= value (help).
  8. Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH; et al. (2013). "Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor". Nature. 503 (7477): 535–8. doi:10.1038/nature12711. PMC 5389864. PMID 24172901.
  9. Turner AJ, Hiscox JA, Hooper NM (2004). "ACE2: from vasopeptidase to SARS virus receptor". Trends Pharmacol Sci. 25 (6): 291–4. doi:10.1016/j.tips.2004.04.001. PMC 7119032 Check |pmc= value (help). PMID 15165741.
  10. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O; et al. (2020). "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation". Science. 367 (6483): 1260–1263. doi:10.1126/science.abb2507. PMC 7164637 Check |pmc= value (help). PMID 32075877 Check |pmid= value (help).
  11. Baig AM, Khaleeq A, Ali U, Syeda H (2020). "Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms". ACS Chem Neurosci. 11 (7): 995–998. doi:10.1021/acschemneuro.0c00122. PMC 7094171 Check |pmc= value (help). PMID 32167747 Check |pmid= value (help).
  12. Swanson PA, McGavern DB (2015). "Viral diseases of the central nervous system". Curr Opin Virol. 11: 44–54. doi:10.1016/j.coviro.2014.12.009. PMC 4456224. PMID 25681709.
  13. Wong SH, Lui RN, Sung JJ (2020). "Covid-19 and the digestive system". J Gastroenterol Hepatol. 35 (5): 744–748. doi:10.1111/jgh.15047. PMID 32215956 Check |pmid= value (help).
  14. Alenquer M, Amorim MJ (2015). "Exosome Biogenesis, Regulation, and Function in Viral Infection". Viruses. 7 (9): 5066–83. doi:10.3390/v7092862. PMC 4584306. PMID 26393640.
  15. Tsivgoulis G, Palaiodimou L, Katsanos AH, Caso V, Köhrmann M, Molina C, Cordonnier C, Fischer U, Kelly P, Sharma VK, Chan AC, Zand R, Sarraj A, Schellinger PD, Voumvourakis KI, Grigoriadis N, Alexandrov AV, Tsiodras S (2020). "Neurological manifestations and implications of COVID-19 pandemic". Ther Adv Neurol Disord. 13: 1756286420932036. doi:10.1177/1756286420932036. PMC 7284455 Check |pmc= value (help). PMID 32565914 Check |pmid= value (help).
  16. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J; et al. (2020). "A first case of meningitis/encephalitis associated with SARS-Coronavirus-2". Int J Infect Dis. 94: 55–58. doi:10.1016/j.ijid.2020.03.062. PMC 7195378 Check |pmc= value (help). PMID 32251791 Check |pmid= value (help).
  17. Bernard-Valnet R, Pizzarotti B, Anichini A, Demars Y, Russo E, Schmidhauser M; et al. (2020). "Two patients with acute meningoencephalitis concomitant with SARS-CoV-2 infection". Eur J Neurol. doi:10.1111/ene.14298. PMC 7267660 Check |pmc= value (help). PMID 32383343 Check |pmid= value (help).
  18. Bernard-Valnet R, Pizzarotti B, Anichini A, Demars Y, Russo E, Schmidhauser M; et al. (2020). "Two patients with acute meningoencephalitis concomitant with SARS-CoV-2 infection". Eur J Neurol. doi:10.1111/ene.14298. PMC 7267660 Check |pmc= value (help). PMID 32383343 Check |pmid= value (help).
  19. Chaumont H, Etienne P, Roze E, Couratier C, Roger PM, Lannuzel A (2020). "Acute meningoencephalitis in a patient with COVID-19". Rev Neurol (Paris). 176 (6): 519–521. doi:10.1016/j.neurol.2020.04.014. PMC 7211749 Check |pmc= value (help). PMID 32414534 Check |pmid= value (help).
  20. Duong L, Xu P, Liu A (2020). "Meningoencephalitis without respiratory failure in a young female patient with COVID-19 infection in Downtown Los Angeles, early April 2020". Brain Behav Immun. 87: 33. doi:10.1016/j.bbi.2020.04.024. PMC 7162766 Check |pmc= value (help). PMID 32305574 Check |pmid= value (help).
  21. 21.0 21.1 Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ (November 2004). "Practice guidelines for the management of bacterial meningitis". Clin. Infect. Dis. 39 (9): 1267–84. doi:10.1086/425368. PMID 15494903.
  22. Chaudhuri A, Martinez-Martin P, Martin PM, Kennedy PG, Andrew Seaton R, Portegies P, Bojar M, Steiner I (July 2008). "EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS Task Force on acute bacterial meningitis in older children and adults". Eur. J. Neurol. 15 (7): 649–59. doi:10.1111/j.1468-1331.2008.02193.x. PMID 18582342.
  23. 23.0 23.1 Le Rhun E, Taillibert S, Chamberlain MC (2013). "Carcinomatous meningitis: Leptomeningeal metastases in solid tumors". Surg Neurol Int. 4 (Suppl 4): S265–88. doi:10.4103/2152-7806.111304. PMC 3656567. PMID 23717798.
  24. 24.0 24.1 Chow E, Troy SB (2014). "The differential diagnosis of hypoglycorrhachia in adult patients". Am J Med Sci. 348 (3): 186–90. doi:10.1097/MAJ.0000000000000217. PMC 4065645. PMID 24326618.
  25. 25.0 25.1 Leen WG, Willemsen MA, Wevers RA, Verbeek MM (2012). "Cerebrospinal fluid glucose and lactate: age-specific reference values and implications for clinical practice". PLoS One. 7 (8): e42745. doi:10.1371/journal.pone.0042745. PMC 3412827. PMID 22880096.
  26. 26.0 26.1 26.2 Negrini B, Kelleher KJ, Wald ER (2000). "Cerebrospinal fluid findings in aseptic versus bacterial meningitis". Pediatrics. 105 (2): 316–9. PMID 10654948.
  27. Brouwer MC, Tunkel AR, van de Beek D (2010). "Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis". Clin Microbiol Rev. 23 (3): 467–92. doi:10.1128/CMR.00070-09. PMC 2901656. PMID 20610819.
  28. Caudie C, Tholance Y, Quadrio I, Peysson S (2010). "[Contribution of CSF analysis to diagnosis and follow-up of tuberculous meningitis]". Ann Biol Clin (Paris). 68 (1): 107–11. doi:10.1684/abc.2010.0407. PMID 20146981.
  29. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J; et al. (2020). "A first case of meningitis/encephalitis associated with SARS-Coronavirus-2". Int J Infect Dis. 94: 55–58. doi:10.1016/j.ijid.2020.03.062. PMC 7195378 Check |pmc= value (help). PMID 32251791 Check |pmid= value (help).
  30. Russell CD, Millar JE, Baillie JK (February 2020). "Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury". Lancet. 395 (10223): 473–475. doi:10.1016/S0140-6736(20)30317-2. PMC 7134694 Check |pmc= value (help). PMID 32043983 Check |pmid= value (help).
  31. Russell B, Moss C, George G, Santaolalla A, Cope A, Papa S; et al. (2020). "Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence". Ecancermedicalscience. 14: 1022. doi:10.3332/ecancer.2020.1022. PMC 7105343 Check |pmc= value (help). PMID 32256705 Check |pmid= value (help).
  32. Ueda R, Saito Y, Ohno K, Maruta K, Matsunami K, Saiki Y, Sokota T, Sugihara S, Nishimura Y, Tamasaki A, Narita A, Imamura A, Maegaki Y (May 2015). "Effect of levetiracetam in acute encephalitis with refractory, repetitive partial seizures during acute and chronic phase". Brain Dev. 37 (5): 471–7. doi:10.1016/j.braindev.2014.08.003. PMID 25174548.
  33. 33.0 33.1 Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K (2020). "COVID-19-Associated Encephalitis Mimicking Glial Tumor". World Neurosurg. 140: 46–48. doi:10.1016/j.wneu.2020.05.194. PMC 7256557 Check |pmc= value (help). PMID 32479911 Check |pmid= value (help).
  34. [+https://clinicaltrials.gov/ct2/show/NCT04372186 "A Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Participants With COVID-19 Pneumonia - Full Text View - ClinicalTrials.gov"] Check |url= value (help).
  35. Zhang C, Wu Z, Li JW, Zhao H, Wang GQ (2020). "Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality". Int J Antimicrob Agents. 55 (5): 105954. doi:10.1016/j.ijantimicag.2020.105954. PMC 7118634 Check |pmc= value (help). PMID 32234467 Check |pmid= value (help).