In vivo (human) and in vitro inactivation of SARS-CoV-2 with 0.5% povidone-iodine nasal spray

Background: Nasal disinfection with 0.5% povidone-iodine (PVP-I) may be a useful adjunct in the management of COVID-19. The purpose of this article is to confirm the in vitro activity of the PVP-I nasal spray against SARS-CoV-2 and whether that may translate into reduced nasal shedding in vivo. Methods: Two SARS-CoV-2 virus isolates were exposed to 0.5% PVP-nasal spray (Nasodine®) for different times in vitro, with PCR and cell culture used to assess impact on viral infectivity and RNA copies. An open label in vivo single arm pilot study of 14 subjects with positive COVID-19 PCR diagnosis was undertaken. Baseline nasal swabs were collected to quantify SARS-CoV-2 pre-treatment, followed by a single 0.5% PVP nasal spray application (1.12 mL). Nasal swabs were collected at 5, 15, and 60 minutes post-dose to assess immediate and residual impact of treatment. Results: In vitro, the nasal spray reduced infectivity by 3.5 log10 TCID50/mL (99.97%) after 15 seconds exposure and eliminated detectable viral infectivity after 60 seconds; there was no effect on viral RNA detection by PCR. In vivo, culturable virus (VOC beta/B.1.351 variant) was obtained from 6 of 14 PCRconfirmed positive subjects; in these subjects, 5 minutes after the single PVP-I dose, the mean viral titre was reduced by 65% versus baseline and by 79% versus baseline at 60 minutes post-dose. 5 of the 6 subjects (83%), had reduction or cessation of viral shedding at 5 minutes in all 6 subjects, virus titers 60 minutes post-dose were below baseline value. 0.5% PVP-I treatment didn’t interfere with the laboratory diagnosis of COVID-19 via PCR-detection of viral RNA in humans. Conclusions: 0.5% PVP-I nasal spray is rapidly virucidal to SARS-CoV-2 in vitro using exposure times consistent with nasal residence; single in vivo nasal administration reduced infectious viral titers in COVID-19 subjects with culturable virus. A single application of 0.5% PVP-I nasal spray does not interfere with PCR-mediated laboratory diagnosis of COVID-19. We are undertaking a large double blinded randomized controlled trial to confirm if repeated application of 0.5% PVP-I nasal spray over a longer period could be useful in suppressing viral shedding and transmission risk in COVID-positive patients

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

BACKGROUN

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients