No abstract

Neurocysticercosis due to parenchymal cysts carries a good prognosis regardless of therapy. Extraparenchymal neurocysticercosis (including ventricular, spinal, and subarachnoid types) carries a poorer prognosis. Most extraparenchymal cases present with hydrocephalus. Medical treatment alone in doses and schedules developed for parenchymal disease is frequently unsuccessful. For ventricular disease, most cases can be managed with shunting procedures either alone or together with the administration of antiparasitic agents (e.g., praziquantel or albendazole), without extirpation of the cysts. Subarachnoid disease was formerly associated with a case fatality rate of about 50%. However, with the combination of shunting procedures for hydrocephalus, antiparasitic agents, and, in some cases, surgical extirpation of the cysts, the prognosis is much improved. Spinal cysticercosis can be either leptomeningeal (which responds like subarachnoid disease) or intramedullary. For all forms of neurocysticercosis, the role of antiparasitic agents needs to be better defined.

The on-going coronavirus disease 2019 (COVID-19) pandemic has mobilized a global effort to develop vaccines and therapeutics that inhibit viral entry by inducing or transferring antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). Phase I/II vaccine clinical trials, monoclonal antibodies, and convalescent sera have all shown promise. However, these efforts often require extensive screening with the live virus under onerous high biocontainment conditions (BSL-3). Virus neutralization assays (VNAs) remain the gold standard for evaluating the anti-viral potency of antibodies and entry inhibitors. The proliferation of pseudotyped virus systems that can be used in BSL-2 compatible VNAs is a positive development. Yet, there is marked variability between VNAs and how the findings are presented, making inter-group comparisons difficult. To address these limitations, we developed a standardized VNA using VSVdeltaG based CoV-2-S pseudotyped particles (CoV2pp) that can be robustly produced at scale. We used our CoV2pp to interrogate the role of exogenous and endogenous proteases in CoV-2-S mediated entry and standardized our VNA based on that understanding. Our CoV2pp VNA showed a strong positive correlation with CoV2-S ELISA and live virus neutralizations in a validated set of patient sera. Our system was subsequently validated by three independent groups as an out-of-the-box VNA. More than 120 patient sera were screened, and we report descriptive statistics for absolute (abs) IC50, IC80, and IC90 values from all positive patient sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2+TMPRSS2. When used in combination with our CoV2pp, we can now produce CoV2pp sufficient for 150,000 standardized VNA/week.