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.

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 β2-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.