The association between SARS-CoV-2 infection and neuronal damage: A population-based nested case-control study

Abstract

Objective: To 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. Setting: This study was embedded within the Rhineland Study, an ongoing community-based cohort study in Bonn, Germany Design: Cross-sectional nested case-control study. Participants: Participants 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 measures: Plasma levels of NfL at the time of measurement, as well as change in plasma NfL levels compared to previously measured pre-pandemic levels Results: After 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). Conclusions: Our 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.