Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Etter, Manina Maja; Martins, Tomás A; Kulsvehagen, Laila; Pössnecker, Elisabeth; Duchemin, Wandrille; Hogan, Sabrina A.; Sanabria‐Diaz, Gretel; Müller, Jannis; Chiappini, Alessio; Rychen, Jonathan; Eberhard, Noëmi; Guzman, Raphaël; Mariani, Luigi; Keller, Emanuela; Melie‐García, Lester; Jelčić, Ilijas; Pargger, Hans; Siegemund, Martin; Kühle, Jens; Oechtering, Johanna; Eich, Caroline; Tzankov, Alexandar; Matter, Matthias S.; Yaldizli, Özgür; Lieb, Johanna; Psychogios, Marios; Berkemeier, Caroline; Leuzinger, Karoline; Hirsch, Hans H.; Granziera, Cristina; Pröbstel, Anne‐Katrin; Hütter, Gregor

doi:10.21203/rs.3.rs-1385593/v1

Cited by 2 publications

(1 citation statement)

References 25 publications

(32 reference statements)

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“…Another group proposed perivascular inflammation and subsequent impairment of the blood-brain barrier (BBB) followed by activation of microglia that causes damage to the central nervous system. 66 Although nonspecific neuroinflammation and antineural autoimmune dysregulation are strong potential theories, pathophysiological confirmation is necessary for most patients. 67 Chronic cytokinemia and inflammation can alter BBB permeability and induce neurotoxicity, and autoantibodies generated can alter neurogenesis, neuronal repair, and the function of microglia.…”

Section: Brain Infection and Blood-brain Barrier Damagementioning

confidence: 99%

What Role Does Microthrombosis Play in Long COVID?

Iba,

Connors,

Levy

2023

Semin Thromb Hemost

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Soon after the outbreak of coronavirus disease 2019 (COVID-19), unexplained sustained fatigue, cognitive disturbance, and muscle ache/weakness were reported in patients who had recovered from acute COVID-19 infection. This abnormal condition has been recognized as “long COVID (postacute sequelae of COVID-19 [PASC])” with a prevalence estimated to be from 10 to 20% of convalescent patients. Although the pathophysiology of PASC has been studied, the exact mechanism remains obscure. Microclots in circulation can represent one of the possible causes of PASC. Although hypercoagulability and thrombosis are critical mechanisms of acute COVID-19, recent studies have reported that thromboinflammation continues in some patients, even after the virus has cleared. Viral spike proteins and RNA can be detected months after patients have recovered, findings that may be responsible for persistent thromboinflammation and the development of microclots. Despite this theory, long-term results of anticoagulation, antiplatelet therapy, and vascular endothelial protection are inconsistent, and could not always show beneficial treatment effects. In summary, PASC reflects a heterogeneous condition, and microclots cannot explain all the presenting symptoms. After clarification of the pathomechanisms of each symptom, a symptom- or biomarker-based stratified approach should be considered for future studies.

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Section: Brain Infection and Blood-brain Barrier Damagementioning

confidence: 99%

What Role Does Microthrombosis Play in Long COVID?

Iba,

Connors,

Levy

2023

Semin Thromb Hemost

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The S1 subunits of SARS-CoV-2 variants differentially trigger the IL-6 signaling pathway in human brain endothelial cells and downstream impact on microglia activation

Stangis,

Adesse,

Sharma

et al. 2024

NeuroImmune Pharmacology and Therapeutics

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Objectives Cerebrovascular complications are prevalent in COVID-19 infection and post-COVID conditions; therefore, interactions of SARS-CoV-2 with cerebral microvascular cells became an emerging concern. Methods We examined the inflammatory responses of human brain microvascular endothelial cells (HBMEC), the main structural element of the blood–brain barrier (BBB), following exposure to the S1 subunit of the spike protein of different SARS-CoV-2 variants. Specifically, we used the S1 subunit derived from the D614 variant of SARS-CoV-2, which started widely circulating in March of 2020, and from the Delta variant, which started widely circulating in early 2021. We then further examined the impact of the HBMEC secretome, produced in response to the S1 exposure, on microglial proinflammatory responses. Results Treatment with S1 derived from the D614 variant and from the Delta variant resulted in differential alterations of the IL-6 signaling pathway. Moreover, the HBMEC secretome obtained after exposure to the S1 subunit of the D614 variant activated STAT3 in microglial cells, indicating that proinflammatory signals from endothelial cells can propagate to other cells of the neurovascular unit. Overall, these results indicate the potential for different SARS-CoV-2 variants to induce unique cellular signatures and warrant individualized treatment strategies. The findings from this study also bring further awareness to proinflammatory responses involving brain microvasculature in COVID-19 and demonstrate how the surrounding microglia react to each unique variant derived response.

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Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study

Cited by 2 publications

References 25 publications

What Role Does Microthrombosis Play in Long COVID?

What Role Does Microthrombosis Play in Long COVID?

The S1 subunits of SARS-CoV-2 variants differentially trigger the IL-6 signaling pathway in human brain endothelial cells and downstream impact on microglia activation

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