ABSTRACT
ObjectiveTo assess whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with changes in plasma levels of neurofilament light chain (NfL), an extremely sensitive marker of neuroaxonal damage, in community-dwelling individuals. SettingThis study was embedded within the Rhineland Study, an ongoing community-based cohort study in Bonn, Germany DesignCross-sectional nested case-control study. ParticipantsParticipants were selected based on results from a previously conducted seroprevalence survey within the framework of the Rhineland Study. Cases were defined as those individuals who had had two positive confirmatory test results, including a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (N=21). As controls, a random sample of individuals with a negative ELISA test result (Controls I, N=1117), and those with a borderline or positive ELISA test result who failed confirmatory testing (Controls II, N=68), were selected. Outcome measuresPlasma levels of NfL at the time of measurement, as well as change in plasma NfL levels compared to previously measured pre-pandemic levels ResultsAfter adjustment for age, sex and batch effects, serologically confirmed SARS-CoV-2 infection was neither associated with cross-sectional NfL levels, nor with the magnitude of change from pre-pandemic levels, compared to either of the two control groups. Similarly, after adjustment for age, sex and batch effects, self-reported neurological symptoms - including altered sense of smell or taste, headache, myalgia and fever - were not associated with changes in NfL levels in participants with a serologically confirmed SARS-CoV-2 infection (all p [≥] 0.56). ConclusionsOur findings indicate that mild-to-moderate coronavirus disease-19 is unlikely to be associated with a clinically relevant degree of neuroaxonal damage, even in those cases associated with neurological symptoms.
Subject(s)
Headache , Fever , Severe Acute Respiratory Syndrome , Nervous System Diseases , Nerve Degeneration , Myalgia , COVID-19 , Neuroaxonal DystrophiesABSTRACT
BACKGROUND. Neurological complications occur in COVID-19. We aimed to examine cerebrospinal fluid (CSF) of COVID-19 subjects with neurological complications and determine presence of neuroinflammatory changes implicated in pathogenesis. 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 (critical, severe, moderate, mild). COVID-19 CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders and stroke controls (n=82). Cytokines (IL-6, TNF-alpha, IFN-gamma, 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 a paucity of neuroinflammatory changes, absence of pleocytosis or specific increases in pro-inflammatory markers or cytokines (IL-6, ferritin, or D-dimer). Anti-SARS-CoV2 antibodies in CSF of COVID-19 subjects (77%) were observed despite no evidence of SARS-CoV2 viral RNA. A similar increase of pro-inflammatory cytokines (IL-6, TNF-alpha;, IL-12p70) and IL-10 in CSF of COVID-19 and non-COVID-19 stroke subjects was observed compared to controls. CSF-NF-L was elevated in subjects with stroke and critical COVID-19. CSF-hsCRP was present almost exclusively in COVID-19 cases. 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. Elevated CSF-NF-L indicates neuroaxonal injury in COVID-19 cases. The role of CSF SARS-CoV2 IgG antibodies is still undetermined.