SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Abstract:

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the virus’s acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis.

Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spike’s persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway.

Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities.

Source: Zhouyi RongHongcheng MaiSaketh KapoorVictor G. PuellesJan CzogallaJulia SchädlerJessica VeringClaire DelbridgeHanno SteinkeHannah FrenzelKatja SchmidtÖzüm Sehnaz CaliskanJochen Martin WettengelFatma CherifMayar AliZeynep Ilgin KolabasSelin UlukayaIzabela HorvathShan ZhaoNatalie KrahmerSabina TahirovicAli Önder YildirimTobias B. HuberBenjamin OndruschkaIngo BechmannGregor EbertUlrike ProtzerHarsharan Singh BhatiaFarida HellalAli Ertürk. SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19.

Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study

Abstract:

OBJECTIVE: To test the hypotheses that patients exposed to viral meningitis would be at an increased risk of developing chronic fatigue syndrome and would have an excess of neurological symptoms and physical impairment.

METHODS: Eighty three patients were followed up 6-24 months after viral meningitis and a postal questionnaire was used to compare outcome with 76 controls who had had non-enteroviral, non-CNS viral infections.

RESULTS: For the 159 patients and controls the prevalence of chronic fatigue syndrome was 12.6%, a rate higher than previously reported from primary care attenders, suggesting that moderate to severe viral infections may play a part in the aetiology of some fatigue states. Those with a history of meningitis showed a slight, non-significant increase in prevalence of chronic fatigue syndrome (OR 1.4; 95% CI 0.5-3.6) which disappeared when logistic regression and analysis was used to correct for age, sex, and duration of follow up (OR 1.0; 95% CI 0.3-2.8). Controls showed marginally higher psychiatric morbidity measured on the general health questionnaire-12 (adjusted OR 0.6; 95% CI 0.3-1.3) Both groups had similar rates of neurological symptoms and physical impairment. The best predictor of chronic fatigue was a prolonged duration time of off work after the illness (OR 4.93, 95% CI 1.3-18.8). The best predictor of severe chronic fatigue syndrome diagnosed by Center for Disease Control criteria was past psychiatric illness (OR 7.82, 95% CI 1.8-34.3). Duration of viral illness, as defined by days in hospital, did not predict chronic fatigue syndrome.

CONCLUSIONS: (1) The prevalence of chronic fatigue syndrome is higher than expected for the range of viral illnesses examined; (2) enteroviral infection is unlikely to be a specific risk factor for its development; (3) onset of chronic fatigue syndrome after a viral infection is predicted by psychiatric morbidity and prolonged convalescence, rather than by the severity of the viral illness itself.

 

Source: Hotopf M, Noah N, Wessely S. Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study. J Neurol Neurosurg Psychiatry. 1996 May;60(5):504-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC486361/ (Full article)