Viral Antigen Detected in Cerebrospinal Fluid of COVID Patients

Neurologic symptoms are common in patients hospitalized with COVID-19 and include anosmia, encephalopathy, encephalitis, and cerebrovascular manifestations, including stroke. The neuroinvasive capacity of SARS-CoV-2 is questionable.

The cause of the cerebrospinal fluid (CSF) immune response in COVID-19 in the absence of detectable viral RNA is not clear. SARS-CoV-2 viral nucleocapsid antigen (N-Ag) can be detected in plasma during the acute phase of infection and is potentially useful as a diagnostic as well as prognostic marker in COVID-19.

An international team of medical scientists collaborating with the Sahlgrenska University Hospital (Gothenburg, Sweden) carried out prospective cross-sectional study that included 44 COVID patients, 21 were neuroasymptomatic and 23 were neurosymptomatic; 21 of the 23 neurosymptomatic patients had encephalopathy, one had encephalitis, and one had Guillain-Barré syndrome. They also assessed and 10 healthy controls and 41 COVID-negative patient controls. Median age of COVID patients was 57, and 68% were men.

SARS-CoV-2 infection was confirmed by viral RNA detection in real-time polymerase chain reaction assays of nasopharyngeal swab or plasma specimens or in-hospital seroconversion. Detection of SARS-CoV-2 nucleocapsid and spike proteins was performed using MSD SPLEX CoV-2 N and MSD S-PLEX CoV-2 S assay kits (Meso Scale Discovery, Rockville, MD. USA). IgG and albumin concentrations were measured by immunoturbidimetry on a Cobas instrument (Roche Diagnostics, Rotkreuz, Switzerland). Cerebrospinal fluid neopterin was measured using a commercially available immunoassay (Brahms Diagnostics, Hennigsdorf, Germany). Cerebrospinal fluid β2-microglobulin (β2M) was measured using the N latex β2M kit on the Atellica NEPH 630 System (Siemens Healthcare GmbH, Erlangen, Germany).

The team reported that all CSF samples tested negative for SARS-CoV-2 RNA. Nucleocapsid antigen was detected in 31 of 35 patients and was significantly correlated with CSF neopterin and interferon γ. No differences in CSF nucleocapsid antigen concentrations were seen in patient groups. COVID patients had markedly increased CSF neopterin, β2-microglobulin, interleukin (IL)-2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median CSF interferon γ (86 fg/mL versus 21 fg/mL). Median CSF concentrations of neurofilament light (NfL), a marker of axonal injury, were higher in COVID patients compared with controls (960 618 ng/L versus 618 ng/L).

The authors concluded that although CSF nucleocapsid antigen concentrations were not significantly different between patient groups, patients with COVID-19 had higher concentrations of CSF NfL compared with controls, and neurosymptomatic patients had a more marked immune activation biomarker profile, suggesting that the magnitude of the central nervous system immune response, possibly triggered by viral components, contributes to the neuropathogenesis of COVID-19. The study was published on May 23, 2022 in the journal JAMA Network Open.

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