ABSTRACT
Background-Aim: A 46 years old housewife patient with a bachelor's degree in Law contracted Covid-19 at the end of March 2021. She had a flu-like form with associated asthenia and drowsiness and no lack of sense of smell. It has been resolved in 25 days. Later, she developed progressive immediate memory loss, word-finding issues, motor and thinking slowing down. Methods: CT brain scan appeared as within the norm as well as liver enzymes, TSH, Vitamin B12, Folate and Rapid Plasma Reagine. Anti- ENA DNA ANA HIV TPO TG were negative too. In October, the patient had a further neuropsychological assessment that showed an overall picture characterized by partial orientation to space, working memory disorders, writing and comprehension (of complex tasks) issues, and immediate memory loss (possible sign both of attention span and concentration reduction). The auto-antibodies were assessed in November and they resulted negative. Moreover, the brain MRI scan and EEG (dated at the end of November) were both within the range. CSF neurodegenerative biomarkers and anti-neuronal antibodies appeared in the norm too. Results: Ultimately, in December 2021 she underwent an 18F-FDG PET brain scan and the SPM analysis showed an extensive hypometabolism in the bilateral frontal cortex and bilateral straight gyrus. Spared the cingulate cortex. Conclusions: The patient contracted Covid in March 2021. She developed neurological deterioration identified by FDG-PET. Negative autoantibodies and CSF biomarkers. PET scan was the only exam to define the brain damage in the patient above. Symmetrical bilateral frontal cortex and bilateral straight gyrus hypo-metabolism have been observed, the last one at the direct level of the olfactory bulb. In this area, in patients who died from Covid-19 it has been histologically demonstrated (data to be published) the presence of cellular inclusions named Corpore Amylacea. They would be a small hyaline mass that functions as a waste container that accumulates in the human brain in aging and in neurodegenerative and infectious processes. It is hypothesized to be that it can be involved in a sort of brain cleaning process1. Recently it has been described that they contain some neoepitopes that are recognized by natural IgMs, revealing a possible link between them and the natural immune system2. However, to now in our patient, the only diagnostic tool to evaluate the brain condition has been the 18F-FDG PET.
ABSTRACT
Introduction: In patients with Multiple Sclerosis (pwMS) disease- modifying therapies (DMTs) are known to affect immune response to antigens and possibly to SARS-CoV2 vaccine. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. Objectives and aims: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARSCov- 2 vaccination with mRNA vaccines (BNT162b2, Pfizer/ BioNTech, Inc or mRNA-1273, Moderna Tx, Inc) to evaluate their effect on SARS-CoV-2 antibody response. Methods: A blood collection for the measure of SARS-CoV-2 antibody before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized and blinded serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche Diagnostics). Results: Preliminary data were collected on 780 pwMS (76% BNT162b2 and 24% mRNA-1273) who had pre- and 4-week post-vaccination blood assessments. 87 (11.2%) were untreated, 154 (19.7%) on ocrelizumab, 25 (3.2%) on rituximab, 85 (10.9%) on fingolimod, 25 (3.2%) on cladribine and 404 (51.7%) on other DMTs. 677 patients (86.8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariate analysis, the antibody levels of patients on ocrelizumab (178-fold decrease, p<0.001), fingolimod (26-fold decrease, p<0.001) and rituximab (17-fold decrease, p<0.001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3.5-fold higher antibody level than with the BNT162b2 vaccine (p<0.001). Interpretation: In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3.5-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those that will be produced by studying the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS. At the time of the ECTRIMS presentation data on the full sample (about 2000 subjects) will be presented.