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.
BACKGROUND
The anaerobe Parvimonas micra is usually recovered as part of the normal flora or in polymicrobial infections of odontogenic or gastrointestinal origin. P. micra has rarely been described as the causative organism of pyogenic spondylodiscitis. Here we report multiple cases of spondylodiscitis caused by this organism and compare their clinical features with the published literature.
METHODS
We performed a retrospective review of all institutional cases with P. micra spondylodiscitis between 01 June 2012 and 31 May 2019. For comparison, the literature was searched for studies reporting vertebral infections with P. micra in adult patients.
RESULTS
Over 7 years, six cases were identified: one with a polymicrobial infection (with P. micra and Fusobacterium nucleatum) and five with P. micra as the only pathogen isolated. The six patients with P. micra infections were between 63 and 82 years old (median 72 years) and presented with persistent lower back pain. Common findings were infection of the lumbar spine region (in 6/6 cases) and recent dental inflammation (4/6 cases). 3/6 patients had previously undergone decompressive spinal surgery due to spinal stenosis (2 to 11 years before). In 4/6 cases the organism was detected in blood cultures drawn at admission. Treatment consisted of antibiotics for all patients and additional decompressive surgery due to abscess formation in half the cases. Outcomes were mostly favourable, but persistent pain was a common complaint after resolution of infection.
CONCLUSIONS
P. micra is a rare cause of spondylodiscitis. Nevertheless, recent dental procedures with subsequent back pain should lead to the consideration of possible anaerobic causes of spondylodiscitis. Heightened awareness of this pathogen and improvements in diagnostic methods might lead to higher detection rates.
Growing evidence suggests that coronavirus disease 2019 (COVID-19) is associated with acute and long-term neurological sequelae. However, the underlying pathophysiological mechanisms resulting in central nervous system (CNS) derogation remain unclear, posing both diagnostic and therapeutic challenges. Here, we performed a cross-sectional study (NCT04472013) and multidimensional characterization of cerebrospinal fluid (CSF) and plasma-targeted proteomics in different Neuro-COVID severity classes with corresponding clinical and imaging data. COVID-19 patients displayed a plasma cytokine storm but a non-inflammatory CSF profile. Severely affected patients displayed signs of blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self- and non-self antigens. Also, COVID-19 patients had decreased regional brain volumes associated with specific CSF and plasma parameters. We provide a multiparametric framework of Neuro-COVID severity classifiers. Collectively, this data identified several potentially actionable targets that may be addressed to prevent COVID-19-related neurological sequelae.
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