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Published on: October 20, 2016
CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
Mar Guasp1,2,3, Guillermo Muñoz-Sánchez4, Eugenia Martínez-Hernández1,2
1Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Insights
Neuroinflammation in COVID-19 patients is linked to acute illness severity. However, long-term disability is more associated with neuroaxonal damage markers than acute inflammatory cytokines.
Area of Science:
- Neurology
- Immunology
- Infectious Diseases
Background:
- COVID-19 frequently causes neurological complications like encephalopathy and encephalitis.
- The exact cause, whether viral-induced inflammation or autoimmunity, remains unclear.
- Biomarkers are crucial for understanding neuro-COVID pathogenesis and prognosis.
Purpose of the Study:
- To assess diagnostic and prognostic roles of CSF and serum biomarkers in neuro-COVID.
- To differentiate between inflammatory and autoimmune mechanisms in neuro-COVID.
- To correlate biomarker levels with disease severity and long-term neurological disability.
Main Methods:
- Prospective study of 60 hospitalized neuro-COVID patients.
- Analysis of serum and cerebrospinal fluid (CSF) for cytokines, neural autoantibodies, and neuroaxonal damage markers (14-3-3 protein, neurofilament light [NfL]).
- 18-month follow-up to assess neurological disability.
Main Results:
- Neuro-COVID patients showed elevated IL-18, IL-6, IL-8 in serum and CSF compared to healthy controls.
- Neuroaxonal damage markers (14-3-3, NfL) and specific cytokines correlated with acute COVID-19 severity.
- CSF levels of 14-3-3 and NfL significantly predicted long-term neurological disability at 18 months.
Conclusions:
- The inflammatory response in SARS-CoV-2 infection may involve blood-brain barrier disruption.
- Prognosis for neuro-COVID patients is more dependent on the extent of neuronal damage than acute neuroinflammation.
- Current biomarkers suggest neuronal damage, not acute inflammation, is key for long-term outcomes.
Abstract:
Patients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear. In this study, we aimed to evaluate the diagnostic and prognostic role of CSF and serum biomarkers of inflammation (a wide array of cytokines, antibodies against neural antigens, and IgG oligoclonal bands), and neuroaxonal damage (14-3-3 protein and neurofilament light [NfL]) in patients with acute COVID-19 and associated neurologic manifestations (neuro-COVID). We prospectively included 60 hospitalized neuro-COVID patients, 25 (42%) of them with encephalopathy and 14 (23%) with encephalitis, and followed them for 18 months. We found that, compared to healthy controls (HC), neuro-COVID patients presented elevated levels of IL-18, IL-6, and IL-8 in both serum and CSF. MCP1 was elevated only in CSF, while IL-10, IL-1RA, IP-10, MIG and NfL were increased only in serum. Patients with COVID-associated encephalitis or encephalopathy had distinct serum and CSF cytokine profiles compared with HC, but no differences were found when both clinical groups were compared to each other. Antibodies against neural antigens were negative in both groups. While the levels of neuroaxonal damage markers, 14-3-3 and NfL, and the proinflammatory cytokines IL-18, IL-1RA and IL-8 significantly associated with acute COVID-19 severity, only the levels of 14-3-3 and NfL in CSF significantly correlated with the degree of neurologic disability in the daily activities at 18 months follow-up. Thus, the inflammatory process promoted by SARS-CoV-2 infection might include blood-brain barrier disruption in patients with neurological involvement. In conclusion, the fact that the levels of pro-inflammatory cytokines do not predict the long-term functional outcome suggests that the prognosis is more related to neuronal damage than to the acute neuroinflammatory process.
