Toxic-metabolic encephalopathy: A catch-all for brain dysfunction caused by infection, organ failure, or intoxication. Transmissible spongiform encephalopathy: A collection of diseases all caused by prions, and characterized by "spongy" brain tissue (riddled with holes), impaired locomotion or coordination, and a 100% mortality rate. Includes bovine spongiform encephalopathy (mad cow disease), scrapie, and kuru among others. Neonatal encephalopathy (hypoxic-ischemic encephalopathy): An obstetric form, often occurring due to lack of oxygen in bloodflow to brain-tissue of the fetus during labour or delivery. Salmonella encephalopathy: A form of encephalopathy caused by food poisoning (especially out of peanuts and rotten meat) often resulting in permanent brain damage and nervous system disorders. Encephalomyopathy: A combination of encephalopathy and myopathy. Causes may include mitochondrial disease (particularly MELAS) or chronic hypophosphatemia, as may occur in cystinosis. Creutzfeldt–Jakob disease (CJD; transmissible spongiform encephalopathy). HIV encephalopathy (encephalopathy associated with HIV infection and AIDS, characterized by atrophy and ill-defined white matter hyperintensity). Sepsis-associated encephalopathy (this type can occur in the setting of apparent sepsis, trauma, severe burns, or trauma, even without clear identification of an infection). Epileptic encephalopathies:
Early infantile epileptic encephalopathy (acquired or congenital abnormal cortical development). Early myoclonic epileptic encephalopathy (possibly due to metabolic disorders). Gluten encephalopathy: Focal abnormalities of the white matter (generally area of low perfusion) are appreciated through magnetic resonance. Migraine is the most common symptom reported. Toxicity from chemotherapy
Chemotherapy medication, for example, fludarabine can cause a
permanent severe global encephalopathy.
In April 2020, Lawrence Berkeley National Laboratory conducted a X-ray crystallography study at Virs request to investigate how such antibodies bind to SARS-CoV-2 at the molecular level. The Berkeley Lab data helped Vir identify candidates for further study, and Vir eventually settled on a single candidate antibody, S309. Vir collaborated with GlaxoSmithKline to make various refinements to S309, resulting in sotrovimab.Sotrovimab has been engineered to possess an Fc LS mutation (M428L/N434S) that confers enhanced binding to the neonatal Fc receptor resulting in an extended half-life and potentially enhanced drug distribution to the lungs.Sotrovimab has demonstrated activity via two antiviral mechanisms in vitro, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Clinical efficacy
The pivotal COMET-ICE study is an ongoing, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of sotrovimab in adults with confirmed COVID-19 (mild, early disease with less than five days of symptoms) at risk of disease progression.An interim analysis of this study reported that sotrovimab reduced the risk of hospitalization for more than 24 hours or death by 85% compared with placebo. Overall 1% of people receiving sotrovimab died or required hospitalization for more than 24 hours compared to 7% of people treated with placebo.