Blood-Based Biomarkers for COVID-19-Associated Neurological Outcomes

Abstract

BackgroundThere are no blood screening tests to assess brain molecular alterations linked to neurological alterations in human coronavirus disease 2019 (COVID-19). Evidence indicates long-term brain abnormalities associated with SARS-CoV-2 infection, including cognitive impairment, which may develop into an emerging health problem as many patients are emerging with cognitive abnormalities that may be associated to an increased risk of AD. Promising results from the field of blood-based biomarkers are emerging with the use of extracellular vesicles (EVs). Neuronal-derived EVs (NDEVs) can be isolated from the total pool of EVs in the blood to investigate biomarkers of brain diseases.MethodsIsolation of NDEVs was performed using the ExoQuick ULTRA EV Isolation System, followed by immunoprecipitation with L1CAM antibody. EVs were characterized by nanoparticle tracking analysis, electron microscopy, Exo-Check Array, and ELISA/immunoblotting to detect exosome proteins. Biomarker measurements in the plasma, CSF and EVs from plasma was done by ELISA. A broader analysis of isolated EVs was done by Mass spectrometry.ResultsLevels of cytokines were increased in the blood samples from a cohort of 100 COVID-19 patients compared to controls. We had the opportunity to investigate biomarkers in the CSF of 38 patients and observed that the levels of cytokines and biomarkers of neurodegeneration in CSF samples were increased.ConclusionsCOVID-19 was associated with increases in CSF and blood cytokines and markers of neurodegeneration. A close follow up in patients that developed COVID-19 symptoms is important to determine the long-term consequences of infectionFunding SourceCNPq, FAPERJ, CIHRKeywordsExtracellular Vesicles, Biomarkers, COVID-19 BackgroundThere are no blood screening tests to assess brain molecular alterations linked to neurological alterations in human coronavirus disease 2019 (COVID-19). Evidence indicates long-term brain abnormalities associated with SARS-CoV-2 infection, including cognitive impairment, which may develop into an emerging health problem as many patients are emerging with cognitive abnormalities that may be associated to an increased risk of AD. Promising results from the field of blood-based biomarkers are emerging with the use of extracellular vesicles (EVs). Neuronal-derived EVs (NDEVs) can be isolated from the total pool of EVs in the blood to investigate biomarkers of brain diseases. There are no blood screening tests to assess brain molecular alterations linked to neurological alterations in human coronavirus disease 2019 (COVID-19). Evidence indicates long-term brain abnormalities associated with SARS-CoV-2 infection, including cognitive impairment, which may develop into an emerging health problem as many patients are emerging with cognitive abnormalities that may be associated to an increased risk of AD. Promising results from the field of blood-based biomarkers are emerging with the use of extracellular vesicles (EVs). Neuronal-derived EVs (NDEVs) can be isolated from the total pool of EVs in the blood to investigate biomarkers of brain diseases. MethodsIsolation of NDEVs was performed using the ExoQuick ULTRA EV Isolation System, followed by immunoprecipitation with L1CAM antibody. EVs were characterized by nanoparticle tracking analysis, electron microscopy, Exo-Check Array, and ELISA/immunoblotting to detect exosome proteins. Biomarker measurements in the plasma, CSF and EVs from plasma was done by ELISA. A broader analysis of isolated EVs was done by Mass spectrometry. Isolation of NDEVs was performed using the ExoQuick ULTRA EV Isolation System, followed by immunoprecipitation with L1CAM antibody. EVs were characterized by nanoparticle tracking analysis, electron microscopy, Exo-Check Array, and ELISA/immunoblotting to detect exosome proteins. Biomarker measurements in the plasma, CSF and EVs from plasma was done by ELISA. A broader analysis of isolated EVs was done by Mass spectrometry. ResultsLevels of cytokines were increased in the blood samples from a cohort of 100 COVID-19 patients compared to controls. We had the opportunity to investigate biomarkers in the CSF of 38 patients and observed that the levels of cytokines and biomarkers of neurodegeneration in CSF samples were increased. Levels of cytokines were increased in the blood samples from a cohort of 100 COVID-19 patients compared to controls. We had the opportunity to investigate biomarkers in the CSF of 38 patients and observed that the levels of cytokines and biomarkers of neurodegeneration in CSF samples were increased. ConclusionsCOVID-19 was associated with increases in CSF and blood cytokines and markers of neurodegeneration. A close follow up in patients that developed COVID-19 symptoms is important to determine the long-term consequences of infection COVID-19 was associated with increases in CSF and blood cytokines and markers of neurodegeneration. A close follow up in patients that developed COVID-19 symptoms is important to determine the long-term consequences of infection