TY - JOUR
T1 - Cerebrospinal fluid in COVID-19 neurological complications
T2 - Neuroaxonal damage, anti-SARS-Cov2 antibodies but no evidence of cytokine storm
AU - Hopkins Neuro-COVID-19 Group
AU - Garcia, Maria A.
AU - Barreras, Paula V.
AU - Lewis, Allie
AU - Pinilla, Gabriel
AU - Sokoll, Lori J.
AU - Kickler, Thomas
AU - Mostafa, Heba
AU - Caturegli, Mario
AU - Moghekar, Abhay
AU - Fitzgerald, Kathryn C.
AU - Pardo, Carlos A.
N1 - Funding Information:
This work was supported by NIH R01-NS110122 and The Bart McLean Fund for Neuroimmunology Research .
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/8/15
Y1 - 2021/8/15
N2 - Objective: To study in cerebrospinal fluid (CSF) of COVID-19 subjects if a “cytokine storm” or neuroinflammation are implicated in pathogenesis of neurological complications. Methods: Cross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 subjects with neurological complications categorized by diagnosis (stroke, encephalopathy, headache) and illness severity. COVID-19 CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders and stroke controls (n = 82). Cytokines (IL-6, TNFα, IFNγ, IL-10, IL-12p70, IL-17A), inflammation and coagulation markers (high-sensitivity-C Reactive Protein [hsCRP], ferritin, fibrinogen, D-dimer, Factor VIII) and neurofilament light chain (NF-L), were quantified. SARS-CoV2 RNA and SARS-CoV2 IgG and IgA antibodies in CSF were tested with RT-PCR and ELISA. Results: CSF from COVID-19 subjects showed absence of pleocytosis or specific increases in pro-inflammatory markers (IL-6, ferritin, or D-dimer). Although pro-inflammatory cytokines (IL-6, TNFα, IL-12p70) and IL-10 were increased in CSF of stroke COVID-19 subjects, a similar increase was observed in non-COVID-19 stroke subjects. Anti-SARS-CoV2 antibodies in CSF of COVID-19 subjects (77%) were observed despite no evidence of SARS-CoV2 viral RNA. CSF-NF-L was elevated in subjects with stroke and critical COVID-19 as compared to controls and other COVID-19 severity categories. CSF-hsCRP was present in all subjects with critical stages of COVID-19 (7/18) but only in 1/82 controls. Conclusion: The paucity of neuroinflammatory changes in CSF of COVID-19 subjects and lack of SARS-CoV2 RNA do not support the presumed neurovirulence of SARS-CoV2 or neuroinflammation in pathogenesis of neurological complications in COVID-19. The role of CSF SARS-CoV2 IgG antibodies and mechanisms of neuronal damage are still undetermined.
AB - Objective: To study in cerebrospinal fluid (CSF) of COVID-19 subjects if a “cytokine storm” or neuroinflammation are implicated in pathogenesis of neurological complications. Methods: Cross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 subjects with neurological complications categorized by diagnosis (stroke, encephalopathy, headache) and illness severity. COVID-19 CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders and stroke controls (n = 82). Cytokines (IL-6, TNFα, IFNγ, IL-10, IL-12p70, IL-17A), inflammation and coagulation markers (high-sensitivity-C Reactive Protein [hsCRP], ferritin, fibrinogen, D-dimer, Factor VIII) and neurofilament light chain (NF-L), were quantified. SARS-CoV2 RNA and SARS-CoV2 IgG and IgA antibodies in CSF were tested with RT-PCR and ELISA. Results: CSF from COVID-19 subjects showed absence of pleocytosis or specific increases in pro-inflammatory markers (IL-6, ferritin, or D-dimer). Although pro-inflammatory cytokines (IL-6, TNFα, IL-12p70) and IL-10 were increased in CSF of stroke COVID-19 subjects, a similar increase was observed in non-COVID-19 stroke subjects. Anti-SARS-CoV2 antibodies in CSF of COVID-19 subjects (77%) were observed despite no evidence of SARS-CoV2 viral RNA. CSF-NF-L was elevated in subjects with stroke and critical COVID-19 as compared to controls and other COVID-19 severity categories. CSF-hsCRP was present in all subjects with critical stages of COVID-19 (7/18) but only in 1/82 controls. Conclusion: The paucity of neuroinflammatory changes in CSF of COVID-19 subjects and lack of SARS-CoV2 RNA do not support the presumed neurovirulence of SARS-CoV2 or neuroinflammation in pathogenesis of neurological complications in COVID-19. The role of CSF SARS-CoV2 IgG antibodies and mechanisms of neuronal damage are still undetermined.
KW - COVID-19
KW - Cerebrospinal fluid
KW - Cytokine storm
KW - Cytokines
KW - Neuroinflammation
UR - http://www.scopus.com/inward/record.url?scp=85107138861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107138861&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2021.117517
DO - 10.1016/j.jns.2021.117517
M3 - Article
C2 - 34090021
AN - SCOPUS:85107138861
VL - 427
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
M1 - 117517
ER -