[UNC] opted against mandatory testing for students before their re-entry, stating that widespread testing went against CDC recommendations and that it could “create a false sense of security” . . . Since the pandemic began, 1,138 students and 72 employees have tested positive. The university has performed a total of 4,612 tests.
COVISTAT Inc. and its parent company Ensysce Biosciences Inc., received IND allowance and today initiated a Phase 1 clinical trial of oral nafamostat in healthy volunteers. Nafamostat, an ultra-potent protease inhibitor and an ingredient from Ensysce’s opioid overdose protection platform, is being developed as an oral treatment for COVID-19. The ultimate goal will be to evaluate if nafamostat mesylate (nafamostat), that has been shown to be an inhibitor of SARS-CoV-2 host cell entry through TMPRSS2, will be effective in preventing progression to acute respiratory failure, to due to COVID-19 infection.
Nafamostat has been approved for intravenous use in Japan for pancreatitis and other diseases, signifying assurance in the drug’s safety but has never been approved in the USA. Nafamostat has a novel mechanism of action for treating COVID-19 as a potent protease inhibitor that blocks SARS-CoV-2 viral entry into host cells. Because of this it has antiviral properties against other coronaviruses including the Middle East Respiratory Syndrome (MERS), SARS and now SARS-CoV-2. In addition, nafamostat has anti-inflammatory, anti-coagulant, and mucolytic properties which, in combination, could be vital in helping COVID-19 patients avoid the need for hospitalization.
Objectives. We aimed to measure SARS-CoV-2 serologic responses in children hospitalized with multisystem inflammatory syndrome (MIS-C) compared to COVID-19, Kawasaki Disease (KD) and hospitalized pediatric controls.
Methods. From March 17, 2020 – May 26, 2020, we prospectively identified hospitalized children at Children’s Healthcare of Atlanta with MIS-C (n=10), symptomatic COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike receptor binding domain (RBD) IgM and IgG, full-length spike IgG, and nucleocapsid protein antibodies by quantitative ELISAs and SARS-CoV-2 neutralizing antibodies by live-virus focus reduction neutralization assays. We statistically compared the log-transformed antibody titers among groups and performed linear regression analyses.
Results. All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated with full-length spike IgG antibodies (R2 =0.956, P<0.001), nucleocapsid protein antibodies (R2 =0.846,P<0.001), and neutralizing antibodies (R2 =0.667, P<0.001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer [GMT] 6800, 95% CI 3495-13231) than children with COVID-19 (GMT 626, 95% CI 251-1563, P<0.001), KD (GMT 124, 95% CI 91-170, P<0.001) and hospitalized controls (GMT 85, P<0.001). All children with MIS-C also had detectable RBD IgM antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with erythrocyte sedimentation rate (R2 =0.512, P<0.046) and with hospital (R2 =0.548, P=0.014) and ICU lengths of stay (R2 =0.590, P=0.010).
Conclusion. Quantitative SARS-CoV-2 serology may have a role in establishing the diagnosis of MIS-C, distinguishing it from similar clinical entities, and stratifying risk for adverse outcomes.