- COVID-19 has been linked to neurologic complications such as stroke, autoimmune encephalitis, and Guillain-Barré syndrome.
- In the current study, researchers investigated host markers of the dysregulated immune response.
- The study demonstrated elevated concentrations of brain injury biomarkers in COVID-19 patients, which increased with disease severity during acute infection.
In a recent study published in the journal Brain, researchers reported that brain injury is common in coronavirus disease 2019 (COVID-19) and influenza. In addition, the exaggerated inflammatory response during COVID-19 might drive progression to severe disease.
Delving into the Study
Polymerase chain reaction (PCR)-positive COVID-19 patients admitted to Cambridge University Hospital between March 2020 and March 2021 were included as subjects.A small positive control group was included as a reference for the magnitude of elevations of brain injury biomarkers. This group comprised patients with acute severe traumatic brain injury. Serum samples were collected from admission and convalescence at up to three-time points – acute (< 14 days), sub-acute (15 to 70 days), and convalescent stages (> 80 days).
Patients were categorized as mild, moderate, and severe based on treatment during the acute phase. Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and total tau concentrations were measured in the sera from COVID-19 patients or plasma from influenza patients. Screening of autoantibodies was done using a customized central nervous system protein microarray.
Disclosures from the Study
The researchers obtained 250 samples from 175 COVID-19 patients and control samples from 59 healthy subjects and 45 influenza patients. Seventy COVID-19 patients had mild disease, 72 had moderate disease, and 33 patients had severe disease.Notably, serum concentrations of GFAP and NfL increased with COVID-19 severity at acute and sub-acute time points, consistent with the levels observed in subjects with severe traumatic brain injury.
The researchers also took note that NfL and GFAP concentrations declined with time, albeit some patients showed increased NfL concentration.The increase in total tau concentration did not vary with disease severity. Convalescent levels of serum GFAP and NfL correlated with paired samples collected between 15 and 42 days. COVID-19 patients exhibited obvious IgG reactivity to spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, notably, to the lung surfactant protein A (SFTPA1).
Furthermore, autoantibody profiles of cohorts were compared by determining the number and targets of positive autoantibody hits to specific antigens. COVID-19 patients had higher IgG and IgM autoantibody hits than healthy controls. Increased serum cytokine levels were observed in sub-acute samples, and many convalescent samples had elevated cytokine concentrations above the normal range. There was a positive correlation between serum NfL and GFAP levels and the number of IgG hits. Nonetheless, total tau concentrations were not associated with IgG hits or cytokine profiles. The number of IgM hits was correlated with serum NfL levels but not with total tau or GFAP concentrations.
Uplifted concentrations of brain injury were observed in COVID-19 patients. These upliftment correlated with the presence of autoantibodies and proinflammatory cytokines. Additionally, evidence of a dysregulated immune response even after four months was also found. It meant that brain injury occurred due to general dysregulated immunity and not because of directly pathogenic autoantibodies. Furthermore, data from influenza patients indicated that brain injury during acute SARS-CoV-2 infection was not unique to COVID-19.
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