ABSTRACT
Background: Camostat, an oral protease inhibitor, blocks entry and replication of SARS-CoV-1 and SARS-CoV-2 in vitro. It is approved for therapy of recurrent pancreatitis in several countries. Camostat has an excellent safety profile and repurposing for COVID-19 treatment was proposed. Methods: We conducted a Phase II randomized, placebo-controlled trial of camostat in adult outpatients with confirmed COVID-19 and one or more risk factors for severe disease (including age ≥65 years, severe obesity, hypertension, diabetes, chronic lung, heart or liver disease). Participants were randomized 2:1 to oral camostat 200 mg or matching placebo four times a day for 14 days. Exclusion criteria were end-stage liver disease, severe renal impairment, oxygen saturation ≤94% on room air, and experimental treatment for COVID-19. The primary efficacy endpoint was hospitalization or death within 28 days. Secondary efficacy included positivity for SARS-CoV-2 by PCR on mid-nasal turbinate swabs on days 7 and 15 compared to baseline. Results: We enrolled 295 participants, 57.3% were female, 15.6% Black and 60% Latinx. Mean age was 51 years (18-93 years). Most (75.3%) were randomized ≤5 days after symptom onset. Common risk factors were hypertension (63.4%), chronic lung disease (33.2%) and diabetes (25.4%), with 46.8% having >1 risk factor. With a lower than anticipated event rate, the primary endpoint of hospitalization or death was not significantly different in the camostat (5.3%, 10/194) and placebo groups (6.1%, 6/99;p=0.78). In the intention-to-treat population, there was a trend towards a lower proportion of PCR positivity in the camostat compared to the placebo group at day 7 (65.2% vs. 75.7%, p=0.12) and day 15 (22.0% vs. 34.3%, p=0.06). Similarly, in a post hoc as treated population, fewer participants in the camostat than in the placebo group remained PCR positive at day 7 (64.7%, 88/136 vs. 76.8%, 53/96;p=0.077) and day 15 (21.8%, 29/133, vs. 34.8%, 23/66;p=0.05). Adverse events occurred in 13% of participants in the placebo and 9% in the camostat group. All severe adverse events (5% in both groups) were related to COVID-19. Conclusion: With a low overall event rate, we did not observe a decrease in risk of hospitalization or death in camostat treated outpatients with COVID-19 at risk for severe disease. SARS-CoV-2 PCR turned negative faster on camostat treatment. Camostat was well tolerated.
ABSTRACT
A previously healthy 10-year-old girl, living in a sheep-farming community in South Africa with exposure to dogs, presented to her local hospital with generalised tonic-clonic seizures. The initial clinical assessment and laboratory work-up were unremarkable. When she presented with further seizures 6 months later, attempts to arrange neuroimaging and specialist assessment were unsuccessful owing to restrictions on routine healthcare services during the SARS-CoV-2 nationwide lockdown. Subsequently, 11 months after her first presentation, she developed focal neurological signs suggestive of raised intracranial pressure. A brain computed tomography scan revealed a left-sided cerebral cyst and imminent tonsillar herniation. An emergency burr-hole procedure was performed to relieve the raised intracranial pressure, followed by definitive neurosurgical excision of cysts. Hydatid protoscolices and hooklets were seen on microscopy of cyst fluid, and treatment with albendazole and praziquantel was initiated. While her infection was treated successfully, long-term sequelae including permanent blindness and hemiparesis could potentially have been prevented with early neuroimaging and surgical intervention.