Acute central nervous system inflammation following COVID-19 vaccination: An observational cohort study.

BACKGROUND: Reports suggest a potential association between coronavirus disease 2019 (COVID-19) vaccines and acute central nervous system (CNS) inflammation. OBJECTIVE: The main objective of this study is to describe features of acute CNS inflammation following COVID-19 vaccination. METHODS: A retrospective observational cohort study was performed at the BARLO MS Centre in Toronto, Canada. Clinicians reported acute CNS inflammatory events within 60 days after a COVID-19 vaccine from March 2021 to August 2022. Clinical characteristics were evaluated. RESULTS: Thirty-eight patients (median age 39 (range: 20-82) years; 60.5% female) presented within 0-55 (median 15) days of a receiving a COVID-19 vaccine and were diagnosed with relapsing remitting multiple sclerosis (MS) (n = 16), post-vaccine transverse myelitis (n = 7), clinically isolated syndrome (n = 5), MS relapse (n = 4), tumefactive demyelination (n = 2), myelin oligodendrocyte glycoprotein antibody disease (n = 1), neuromyelitis optica spectrum disorder (n = 1), chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (n = 1) and primary autoimmune cerebellar ataxia (n = 1). Twenty-two received acute treatment and 21 started disease-modifying therapy. Sixteen received subsequent COVID-19 vaccination, of which 87.5% had no new or worsening neurological symptoms. CONCLUSION: To our knowledge, this is the largest study describing acute CNS inflammation after COVID-19 vaccination. We could not determine whether the number of inflammatory events was higher than expected.

Tixagevimab and Cilgavimab (Evusheld™) Prophylaxis Prevents Breakthrough COVID-19 Infections in Immunosuppressed Population: 6-Month Prospective Study.

BACKGROUND: Persons with neuroinflammatory diseases (pwNID) treated with potent immunosuppressives are at risk of severe COVID-19 outcomes and reduced vaccine seroconversion. We aimed at determining the real-world efficacy of tixagevimab and cilgavimab (Evusheld™) in immunosuppressed pwNID in preventing breakthrough COVID-19 infections. METHODS: 31 immunosuppressed pwNID were followed for 6 months after administration of tixagevimab and cilgavimab as a prophylactic COVID-19 medication (January 2022-July 2022). Only pwNID treated with anti-CD20 monoclonal antibodies and sphingosine-1-phosphate modulators were considered eligible for the study. A control group of 126 immunosuppressed pwNID (38 seropositive and 88 seronegative after SARS-CoV-2 vaccination) were included. Breakthrough COVID-19 infections rate and their severity was determined over the follow-up. RESULTS: The pwNID treated with tixagevimab and cilgavimab had more comorbidities when compared with the total and seronegative pwNID control group (54.8% vs. 30.2% vs. 27.3%, p = 0.02 and p = 0.005, respectively). After a 6-month follow-up, significantly lower numbers of pwNID treated with tixagevimab and cilgavimab had breakthrough COVID-19 when compared with the control pwNID group (6.5% vs. 34.1%, p = 0.002) and seronegative control pwNID group (6.5% vs. 38.6%, p < 0.001). All COVID-19 infections in Evusheld-treated pwNID were mild, whereas 9/43 COVID-19 infections in the control group were moderate/severe. No side effects to tixagevimab and cilgavimab were recorded. CONCLUSION: In pwNID treated with immunosuppressive therapies, tixagevimab and cilgavimab (Evusheld™) significantly reduced the numbers and severity of breakthrough COVID-19 infections during the Omicron (BA.2-BA.5 variants) wave.

Cytokine profiles in intensive care unit delirium.

BACKGROUND: Neuroinflammation causing disruption of the blood-brain barrier and immune cell extravasation into the brain parenchyma may cause delirium; however, knowledge of the exact pathophysiologic mechanism remains incomplete. The purpose of our study was to determine whether cytokine profiles differ depending on whether delirium occurs in the setting of sepsis, coronavirus disease 2019 (COVID-19), or recent surgery. METHODS: This prospective observational cohort study involved 119 critically ill patients admitted to a multidisciplinary intensive care unit (ICU) during 2019 and 2020. Delirium was identified using the validated confusion assessment method for the ICU. Multiple delirium risk factors were collected daily including clinical characteristics, hospital course, lab values, vital signs, surgical exposure, drug exposure, and COVID-19 characteristics. Serums samples were collected within 12 hours of ICU admission and cytokine levels were measured. RESULTS: The following proinflammatory cytokines were elevated in our delirium population: tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-18, C-C motif ligand (CCL) 2, CCL3, C-X-C motif chemokine ligand (CXCL)1, CXCL10, IL-8, IL-1 receptor antagonist, and IL-10. Analysis of relative cytokine levels in those patients that developed delirium in the setting of sepsis, COVID-19, and recent surgery showed elevations of CCL2, CXCL10, and TNF-α in both the sepsis and COVID-19 group in comparison to the postsurgical population. In the postsurgical group, granulocyte colony-stimulating factor was elevated and CXCL10 was decreased relative to the opposing groups. CONCLUSIONS: We identify several cytokines and precipitating factors known to be associated with delirium. However, our study suggests that the cytokine profile associated with delirium is variable and contingent upon delirium precipitating factors.