RESUMO
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 is effective against the D614G, B.1.1.7 and B.1.351 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.
RESUMO
BackgroundThe spatial and temporal dynamics of SARS-CoV-2 have been mainly described in form of case series or retrospective studies. In this study, we aimed to provide a coherent overview from published studies of the duration of viral detection and viral load in COVID-19 patients, stratified by specimen type, clinical severity and age. MethodWe systematically searched PubMed/MEDLINE and Cochrane review database for studies published between 1. November 2019 and 23rd of April 2020. We included studies that reported individual viral data over time measuring negative conversion by two consecutive negative tests, individual clinical severity and age. We excluded studies that reported viral data as patient fraction, reported only baseline data, included solely asymptomatic patients or were interventional studies. Extracted data included author, title, design, sample size, thresholds and genes of RT-PCR, patient age, COVID-19 severity, clinical characteristics, treatment, location of viral sampling, duration of viral detection, and viral load. We pooled the data of selected studies to determine effect estimates of duration of viral detection. Combined viral load was visualized over time. FindingsOut of 7226 titles screened, 37 studies met the inclusion criteria and were included in the qualitative analysis and 22 studies in the quantitative analysis comprising 650 COVID-19 patients. The pooled estimate of the duration of positive detection of the virus was in mild adult patients 12.1 days (CI: 10.12, 14.05) after symptom onset in the upper respiratory tract (URT), 24.1 days (CI: 10.02, 38.19) in lower respiratory tract (LRT), and 15.5 days (CI: 8.04, 22.88) in faeces. Further, in mild adult patients, the maximum viral load was ~ 6.61 x 108 viral copies/mL in the URT and ~ 2.69 x 108 viral copies/mL in the LRT, within the first week of symptom onset. The maximum viral load in faeces was reported as ~ 3.55 x 107 copies/mL on Day 9. In moderate-severe adult patients, the pooled estimate of mean duration of positive viral detection in the URT was 15.8 days (CI: 11.12, 20.56) after symptom onset, 23.2 days (CI: 21.49, 24.97) in the LRT, 20.8 days (CI: 16.40, 25.17) in faeces. The maximum viral load was 4.60 x 109 copies/mL on Day 8 in the URT, 3.45 x 108 copies/mL on Day 11 in the LRT, 2.76 x 106 copies/mL on Day 18 in faeces and 1 x 104 copies/mL on Day 3 in blood. In children with mild symptoms, the pooled estimate of the mean duration of positive SARS-CoV-2 viral detection was 11.1 days (CI: 7.14, 15.11) in the URT and 16.0 days (CI: 11.49, 20,47) in the faeces, without reporting quantitative viral data. Viral positivity was detected in the urine and eye in one patient. InterpretationOur analysis showed consistent viral detection from specimen from the URT, the 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, whereas 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 in feces and the URT for moderate-severe patients was shown. Further, viral load was demonstrated to peak in the URT within first weak of infection, whereas maximum viral load has been observed to occur later and within the second week of infection in the LRT. FundingThe project has received funding support from Innovation Fund Denmark.
