Abstract Details

Title Serum And Cerebrospinal Fluid Antibody Signatures Track With Outcome Of Neurologic Post-Acute Sequelae Of SARS-Cov-2 Infection (NeuroPASC)

Topic Infectious Disease

Presentation(s) S21 - Acute and Post-Acute Sequelae of COVID-19 (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

Background Despite being primarily a respiratory pathogen, SARS-CoV-2 can also affect the central nervous system (CNS). SARS-CoV-2-related CNS disturbances have been observed during acute infection, but also at distance from respiratory disease, as neuroPASC. The pathogenesis of neuroPASC remains unclear.

Objective

Determine the role of antibodies and innate immune responses in the pathogenesis of neurologic post-acute sequelae of SARS-CoV2 (neuroPASC).

Design/Methods Using a systems serology approach, we deeply profiled the antibody responses against SARS-CoV-2 and other viruses, including common Coronaviruses, in the serum of SARS-CoV2-infected individuals who developed or not neuroPASC. In neuroPASC, we compared the serum and cerebrospinal fluid (CSF) antibody responses, and identified prognostic factors for good vs bad outcome.

Results

Compared to individuals who did not develop neurological complications following infection (n=94), those with neuroPASC (n=18) showed lower systemic antibody responses against SARS-CoV-2, including antibody-dependent complement deposition (ADCD), NK cell activation (ADNKA) and Fcg receptor binding. No differences in the antibody responses to EBV, Flu or HSV1 were observed. However, surprisingly, NeuroPASC showed expanded antibody responses to other common Coronaviruses, suggesting an original antigenic sin, where pre-existing immune responses against related viruses shape the response to current infection. Also, in neuroPASC, all antibody isotypes/subclasses were detected in the serum, whereas CSF was characterized by IgG1 (and absence of IgM), suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain-barrier, rather than intrathecal synthesis. Finally, CSF SARS-CoV-2 responses were selectively elevated in individuals with good outcome, whereas systemic responses against other common Coronaviruses were enriched in individuals with bad outcome.

Conclusions These data point to the potential critical importance of original antigenic sin in shaping the humoral immune response to SARS-CoV-2 immunity, representing a key prognostic biomarker, especially in the CSF, of neuroPASC disease.

Authors/Disclosures
Marianna Spatola, MD, PhD (FUNDACIÓ DE RECERCA BIOMEDICA CLÍNIC IDIBAPS) PRESENTER	The institution of Dr. Spatola has received research support from Spanish National Health Institute (Carlos III). The institution of Dr. Spatola has received research support from Spanish National Institute of Health - Miguel Servet Grant.
Alessandro Dinoto, MD	The institution of Dr. Dinoto has received research support from Encephalitis International . The institution of Dr. Dinoto has received research support from Autoimmune Encephalitis Alliance.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Sara Mariotto, MD, PhD (Neurology Unit, University of Verona)	Dr. Mariotto has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen, Sanofi, Alexion, TSF, Dynamics. The institution of Dr. Mariotto has received research support from Ministero della Salute Italiano. The institution of Dr. Mariotto has received research support from TSF.
Galit Alter	No disclosure on file