Article
The role of microvesicles and extracellular nucleic acids in neurological manifestations of SARS-Cov-2 infection
Die Rolle von Mikrovesikeln und extracellulären Nukleinsäuren in neurologischen Manifestation der SARS-Cov-2 Infektion
Search Medline for
Authors
-
Ran Xu
- Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
-
Shufan Huo
- Charité – Universitätsmedizin Berlin, Klinik für Neurologie, Berlin, Deutschland
-
Nicolle Kränkel
- Charité – Universitätsmedizin Berlin, Kardiologie, Berlin, Deutschland
-
Anton Früh
- Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
-
Silvia Fischer
- Universitätsklinikum Gießen, Gießen, Deutschland
-
Katharina Tielking
- Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
-
Peter Vajkoczy
- Charité – Universitätsmedizin Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
| Published: | May 25, 2022 |
|---|
Outline
Text
Objective: Neurological symptoms can present relevant co-morbidities in SARS-Cov-2 infection but potential underlying pathomechanistic patterns remain unclear. Interestingly, the presence of SARS-Cov-2 RNA and protein has been shown to in anatomically distinct areas of the brain but remains undetected in cerebrospinal fluid (CSF). This study aimed at investigating the role of extracellular nucleic acids and microvesicles and its potential contribution to neuroinflammation in Covid-19.
Methods: CSF and blood samples from n=8 patients with SARS-Cov-2 infection and associated neurological symptoms were collected. Control samples comprised patients (n=6), in which lumbar puncture was done to rule out meningitis and was negative for infection or any neuroinflammatory pathology. Samples were immediately placed on ice and spun down twice at 4°C at 500g for 5 min. Extracellular RNA (exRNA) and RNase activity was quantified, as well as double-stranded DNA via Sytox Green. Microvesicles were quantified via FACS analysis. Proteomics were analyzed in CSF using the proximity extension assay technology of the Olink Target 96 platform (Figure 1 [Fig. 1]).
Results: Neutrophil extracellular traps as well as extracellular RNA were significantly increased in peripheral blood in Covid-19 patients (p<0.01), while it remained unchanged in CSF. RNase activity was significantly upregulated in peripheral blood (p<0.05) and depleted in CSF (p<0.01). Microvesicles were significantly increased in the CSF of Covid-19 patients (Figure 2 [Fig. 2]). Proteomics showed a distinct neuroinflammatory signature which differed from positive control samples (subarachnoid hemorrhage with increased abundance of inflammatory proteins).
Conclusion: An increase of microvesicles is found in the CSF of Covid-19 patients with neurological symptoms, with a parallel depletion of RNase, and a distinct inflammatory signature, suggesting that turnover of extracellular nucleic acids as well as an increase of MVs might play a mediating role in CNS pathology in SARS-Cov-2 infection.
