Sangharsha Thapa

Background. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that currently lacks reliable diagnostic biomarkers. The meta-analysis is performed with an aim to evaluate the diagnostic potential of cerebrospinal fluid (CSF) total tau (t-tau), phosphorylated-tau (p-tau), and their ratio in ALS patients. Methods. A comprehensive search for literature published between the 1^st of January 2000 and the 15^th of May 2022 was performed in databases PubMed, medRxiv, and Google Scholar. The retrieved articles were first screened by title and abstract, and later, full-text screening was performed based on the eligibility criteria. Data on p-tau and t-tau levels and p-tau/t-tau ratio in ALS patients and controls were extracted, and a meta-analysis was performed using random-effects models in Review Manager version 5.4. Results. Data were analyzed from seven studies reporting p-tau and t-tau levels and their ratio among ALS patients and controls. The number of total study participants was 1,100. In ALS patients, the levels of p-tau didn’t differ significantly with controls (standardized mean difference (SMD): 0.14 (95% CI: -0.41 to 0.70); ). In contrast, there were significantly elevated levels of t-tau and significantly lowered p-tau/t-tau ratio in ALS (SMD: 1.76 (95% CI: 0.53 to 2.98); and SMD: -3.09 (95% CI: -5.33 to -0.86); , respectively). Conclusion. Our meta-analysis study supports the role of core CSF biomarkers of neurodegeneration: t-tau and p-tau/t-tau ratio as a diagnostic biomarker of amyotrophic lateral sclerosis. This study found that t-tau is elevated while p-tau/t-tau ratio is lowered in ALS.

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.