Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study.
Manina M EtterTomás A MartinsLaila KulsvehagenElisabeth PössneckerWandrille DucheminSabrina HoganGretel Sanabria-DiazJannis MüllerAlessio ChiappiniJonathan RychenNoëmi EberhardRaphael GuzmanLuigi MarianiLester Melie-GarciaEmanuela KellerIlijas JelcicHans ParggerMartin SiegemundJens KuhleJohanna OechteringCaroline EichAlexandar TzankovMatthias S MatterSarp UzunÖzgür YaldizliJohanna M LiebMarios-Nikos PsychogiosKaroline LeuzingerHans H HirschCristina GranzieraAnne-Katrin PröbstelGregor HutterPublished in: Nature communications (2022)
Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.
Keyphrases
- sars cov
- coronavirus disease
- blood brain barrier
- cerebrospinal fluid
- respiratory syndrome coronavirus
- liver failure
- cerebral ischemia
- drug induced
- high resolution
- dendritic cells
- newly diagnosed
- respiratory failure
- multiple sclerosis
- end stage renal disease
- early onset
- clinical trial
- intensive care unit
- metabolic syndrome
- skeletal muscle
- inflammatory response
- spinal cord
- spinal cord injury
- hepatitis b virus
- neuropathic pain
- photodynamic therapy
- adipose tissue
- peritoneal dialysis
- big data
- resting state
- aortic dissection
- electronic health record
- insulin resistance
- mechanical ventilation
- extracorporeal membrane oxygenation