COVID-19 in the central nervous system: routes of entry and influence on gliomagenesis

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Abstract

Introduction. The pathogenesis of infection of the central nervous system (CNS) with SARS-CoV2 and nervourological complications are still poorly understood, as well as the link of viral infection with the risk and the course of gliomas.

The aim. Evaluating of the possible involvement of Basigin, NRP1, Cathepsin L and transmembrane proteases TMPRSS2 and TMPRSS4 in coronavirus infection of neurons and gliomagenesis.

Мaterial and methods. histological and immunohistochemical researches with antibodies to Cathepsin L, TMPRSS2, TMPRSS4, NRP1, Vasidin, SARS-CoV-2 of the brain of 6 patients with COVID-19, 3 patients of the «precovid period» (control group) and gliomas of 7 patients operated in 2024.

The results of the research demonstraded that the expression of Basigin and TMPRSS2 was significantly higher in the group of patients with gliomas compared with the other groups (for Basigin pgliomas / COVID-19 = 0.006; pgliomas / control group = 0.038; for TMPRSS2 pgliomas / COVID-19 = 0.040; pgliomas / control group = 0.006). In the group of patients with COVID-19, a negative correlation was found between the prevalence of Cathepsin L and SARS-CoV-2 expression (rs = -0.37, p = 0.009), and Basigin was expressed in 5–25% of glial cells. Cathepsin L and TMPRSS4 demonstrated moderate negative associations in the groups of patients with COVID-19 and gliomas.

Conclusion: Basigin, NRP1, Cathepsin L, TMPRSS2 and TMPRSS4 cannot be used as alternative pathways for more effective penetration of SARS-CoV-2 into neurons. The expression of Basigin and TMPRSS2 was the highest in gliomas significantly. Probably, the coexpression of the virus with Basigin weakens the immunosuppression of tumors; it mays to increase the incidence or recurrence of tumors in patients with COVID-19.

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About the authors

Lyubov B. Mitrofanova

Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: lubamitr@yandex.ru
ORCID iD: 0000-0003-0735-7822

Head of the Department of Pathological Anatomy with Clinic, Chief Researcher, Pathomorphology Research Laboratory, Head of the Pathomorphology Service, Pathologist of the Pathoanatomical Department of the University Clinic, Doctor of Medical Sciences, Professor

Russian Federation, Akkuratova str., 2, Saint Petersburg, 197341

Igor A. Makarov

Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” of the Ministry of Health of the Russian Federation

Email: doctormakarovia@gmail.com
ORCID iD: 0000-0001-6175-8403

Аssistant, Department of Pathological Anatomy with clinic, Pathologist of the Pathology Department of the University Clinic, Candidate of Medical Sciences

Russian Federation, Akkuratova str., 2, Saint Petersburg, 197341

Ksenia A. Guseva

Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” of the Ministry of Health of the Russian Federation

Email: ksuha.gus@yandex.ru
ORCID iD: 0009-0009-4477-9128

Clinical Resident, Department of Pathological Anatomy with clinic

Russian Federation, Akkuratova str., 2, Saint Petersburg, 197341

Irina A. Danilova

Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” of the Ministry of Health of the Russian Federation

Email: imd@rambler.ru
ORCID iD: 0000-0003-0865-5936

Pathologist, Professor, Department of Pathological Anatomy of the Clinic of the Ministry of Health of the Russian Federation, Doctor of Medical Sciences, Professor

Russian Federation, Akkuratova str., 2, Saint Petersburg, 197341

Dmitry A. Gulyaev

Federal State Budgetary Institution “V.A. Almazov National Medical Research Centre” of the Ministry of Health of the Russian Federation

Email: gulyaevd@mail.ru
ORCID iD: 0000-0002-5509-5612

Professor of the Department of Neurosurgery, Head of Neurosurgical Department No.5, Neurosurgeon, Neurosurgical Department No.5, Head of the Research Institute of Integrative Neurosurgical Technologies, Doctor of Medical Sciences, Professor, Associate Professor

Russian Federation, Akkuratova str., 2, Saint Petersburg, 197341

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2. Fig. 1. Patient from the control group, 65 years old. Expression of NRP1 (а), basigin (б), cathepsin L (в), TMPRSS2 (г), TMPRSS4 (д) in the temporal lobe of the brain; ×200

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3. Fig. 2. Patient with COVID-19, 67 years old. Hematoxylin and eosin staining of the temporal lobe cortex (а), expression of NRP1 (б), basigin (в), cathepsin L (г), TMPRSS2 (д), TMPRSS4 (е); ×200

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4. Fig. 3. Patient with small cell glioblastoma Grade 4, 48 years old. а – hematoxylin and eosin staining; expression of NRP1 (б), basigin (в), cathepsin L (г), TMPRSS2 (д), TMPRSS4 (е); ×200

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5. Fig. 4. Expression of SARS-CoV2: а – in an 86-year-old patient with COVID-19 on neurons and glial cells of the temporal lobe cortex; ×100; б – on astrocytoma cells, Grade 4; ×200

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6. Fig. 5. Statistically significant differences in the expression of the studied markers between groups

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7. Fig. 6. Heat matrices of correlations between the studied IHCI markers in groups of patients with COVID-19 and patients with gliomas

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8. Table 1 Clinical data of the examined patients

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9. Table 2 The average relative number of cells of the temporal lobe cortex (%) with the expression of immunohistochemical markers in patients with coronavirus infection and gliomas

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