Kidney Transplant and Dialysis Patients Remain at Increased Risk for Succumbing to COVID-19.

BACKGROUND: Immunocompromised patients have been at an increased risk of succumbing to coronavirus disease 2019 (COVID-19) since the beginning of the pandemic. METHODS: Here, we analyzed mortality and case fatality data from dialysis and kidney transplant patients, and compared each with an age-matched subgroup of the general population. RESULTS: We found that both patients on dialysis and kidney transplant patients remain at increased risk of succumbing to COVID-19 despite all available countermeasures. CONCLUSIONS: The analyses underline the need for additional protection for this vulnerable population.

Niclosamide-A promising treatment for COVID-19.

Vaccines have reduced the transmission and severity of COVID-19, but there remains a paucity of efficacious treatment for drug-resistant strains and more susceptible individuals, particularly those who mount a suboptimal vaccine response, either due to underlying health conditions or concomitant therapies. Repurposing existing drugs is a timely, safe and scientifically robust method for treating pandemics, such as COVID-19. Here, we review the pharmacology and scientific rationale for repurposing niclosamide, an anti-helminth already in human use as a treatment for COVID-19. In addition, its potent antiviral activity, niclosamide has shown pleiotropic anti-inflammatory, antibacterial, bronchodilatory and anticancer effects in numerous preclinical and early clinical studies. The advantages and rationale for nebulized and intranasal formulations of niclosamide, which target the site of the primary infection in COVID-19, are reviewed. Finally, we give an overview of ongoing clinical trials investigating niclosamide as a promising candidate against SARS-CoV-2.

Niclosamide shows strong antiviral activity in a human airway model of SARS-CoV-2 infection and a conserved potency against the Alpha (B.1.1.7), Beta (B.1.351) and Delta variant (B.1.617.2).

SARS-CoV-2 variants are emerging with potential increased transmissibility highlighting the great unmet medical need for new therapies. Niclosamide is a potent anti-SARS-CoV-2 agent that has advanced in clinical development. We validate the potent antiviral efficacy of niclosamide in a SARS-CoV-2 human airway model. Furthermore, niclosamide remains its potency against the D614G, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants. Our data further support the potent anti-SARS-CoV-2 properties of niclosamide and highlights its great potential as a therapeutic agent for COVID-19.

A randomized, double-blind, placebo-controlled phase 1 trial of inhaled and intranasal niclosamide: A broad spectrum antiviral candidate for treatment of COVID-19.

BACKGROUND: Coronavirus disease 19 (COVID-19) is spreading globally and treatment options remain limited. A formulation of niclosamide, a potent anti-SARS-CoV-2 agent and a broad-spectrum antiviral treatment candidate, optimized for inhalation and intranasal administration (UNI91104) was developed. METHODS: We conducted a randomized, placebo-controlled, double-blind, single-centre, dose-ascending Phase 1 trial to assess the safety of UNI91104 in Denmark (NCT04576312). Healthy volunteers were randomly assigned to a ascending single dose in cohort 1-4 and five doses over 2.5 days in cohort 5. Inclusion criteria included a minimum 80% of predicted lung function. Exclusion criteria included severe, clinically significant allergies and current acute or chronic condition especially airway diseases. Safety was evaluated through adverse events (AEs) and pulmonary function tests including forced expiratory volume in one second (FEV1) and fractional exhaled nitric oxide (FeNO) tests. The primary endpoints were defined as the frequency of reported AEs and the change of safety variables relative to pre-dose. Data from all enroled healthy volunteers receiving any amount of IMP was included in the primary analyses. The pharmacokinetics of UNI91104 was determined. FINDINGS: The trial was conducted between 29 June 2020 and 08 August 2020. Thirty-four healthy volunteers received UNI91104 and ten placebo. No serious AEs or discontinuation were reported. Mild irritation in the upper respiratory tract following inhalation of UNI91104 was reported as most frequent AE (45 events in 26 healthy volunteers, 59% of all healthy volunteers). Nasal application was well-tolerated. There was no evidence of difference in the change of mean levels of pulmonary function tests between active and placebo group across all cohorts. Five healthy volunteers (11.4%) (1 on placebo) had signs of increased transient FeNO and 4 on active (9.1%) experienced asymptomatic drops in FEV1, which resolved spontaneously or were reversible with a ß2-agonist. Niclosamide exhibited dose-proportional pharmacokinetics following inhalation and intranasal administration. INTERPRETATION: UNI91104, a promising candidate for inhalation and intranasal therapy against COVID-19 and other viral respiratory tract infections is well-tolerated in healthy volunteers and warrants further testing in patient trials. FUNDING: The study was funded by Innovationsfonden Denmark and UNION therapeutics.

Clinical features of patients with acute coronary syndrome during the COVID-19 pandemic.

Although a reduction in hospital admissions of acute coronary syndromes (ACS) patients has been observed globally during the coronavirus disease 2019 (COVID-19) pandemic, clinical features of those patients have not been fully investigated. The aim of the present analysis is to investigate the incidence, clinical presentation, and outcomes of patients with ACS during the COVID-19 pandemic. We performed a retrospective analysis of consecutive patients who were admitted for ACS at our institution between March 1 and April 20, 2020 and compared with the equivalent period in 2019. Admissions for acute myocardial infarction (AMI) reduced by 39.5% in 2020 compared with the equivalent period in 2019. Owing to the emergency medical services (EMS) of our region, all time components of ST-elevated myocardial infarction care were similar during the COVID-19 outbreak as compared with the previous year's dataset. Among the 106 ACS patients in 2020, 7 patients tested positive for COVID-19. Higher incidence of type 2 myocardial infarction (29% vs. 4%, p = 0.0497) and elevated D-dimer levels (5650 µg/l [interquartile range (IQR) 1905-13,625 µg/l] vs. 400 µg/l [IQR 270-1050 µg/l], p = 0.02) were observed in COVID-19 patients. In sum, a significant reduction in admission for AMI was observed during the COVID-19 pandemic. COVID-19 patients were characterized by elevated D-dimer levels on admission, reflecting enhanced COVID-19 related thrombogenicity. The prehospital evaluation by EMS may have played an important role for the timely revascularization for STEMI patients.

Spatial and temporal dynamics of SARS-CoV-2 in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: The spatial and temporal dynamics of SARS-CoV-2 have been described in case series and retrospective studies. In this study, we provide a coherent overview of the duration of viral detection and viral RNA load in COVID-19 patients, stratified by specimen type, clinical severity, and age. METHOD: We systematically searched PubMed/MEDLINE and Cochrane review database for studies published between 1.11.2019 and 23.04.2020. We pooled the data of selected studies (22/7226 (650 patients) for meta-analysis) to estimate duration of viral detection and visualized viral load over time. FINDINGS: Our analysis showed consistent viral detection from specimen from the upper respiratory tract (URT), the lower respiratory tract (LRT), and faeces, irrespective of the clinical severity of COVID-19. Our analysis suggests that SARS-CoV-2 persists for a longer duration in the LRT compared to the URT in adult patients (5•7 days in mild; 5•9 days in moderate-severe patients). The differences in the duration of viral detection between mild and moderate-severe patients is limited in the LRT, but an indication of longer duration of viral detection for moderate-severe patients was observed in feces (15 days in mild vs. 21 days in moderate-severe patients) and the URT (12 days in mild vs. 16 days in moderate-severe patients). Further, viral load was demonstrated to peak in earlier stages of infection in the URT compared to LRT. INTERPRETATION: This review may aid mathematical modelling and help in defining appropriate endpoints for clinical trails with antivirals in COVID-19. FUNDING: The project has received funding support from Innovation Fund Denmark.