ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models.

Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19.

A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model.

BACKGROUND: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. METHODS: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). FINDINGS: We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals. INTERPRETATION: The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT, to reduce SARS-CoV-2 transmission and provide protection against COVID-19. FUNDING: This work was funded by Ena Respiratory, Melbourne, Australia.

Validation of ROPScore to predict retinopathy of prematurity among very low birth weight preterm infants in a southern Brazilian population / Validação de um escore (ROPScore) capaz de prever a ocorrência da retinopatia da prematuridade em prematuros de baixo peso no sul do Brasil

ABSTRACT Purposes: To evaluate the sensitivity, specificity, and cutoff points for the ROPScore, which is based on cumulative risk factors for the prediction of retinopathy of prematurity (ROP), in a population of very low birth weight (BW) preterm infants in southern Brazil. Methods: The medical records of all preterm infants with a very low birth weight ≤1,500 g and/or gestational age ≤32 weeks screened for retinopathy of prematurity in two Brazilian institutions between August 2009 and December 2015 were retrospectively reviewed. ROPScores were calculated using birth weight and gestational age, the use of oxygen therapy with mechanical ventilation, and weight gain proportional to birth weight, as measured at postpartum week six and the need for blood transfusions. Results: The study cohort included 322 infants with a mean birth weight of 1181.8 ± 292.5 g and mean gestational age of 29.5 ± 2.3 weeks. The incidences of any stage of retinopathy of prematurity and severe retinopathy of prematurity were 68.3% and 17%, respectively. ROPScore values ranged from 8.7 to 19.9. The best cutoff point for sensitivity and specificity was 11 for any stage of retinopathy of prematurity and 14.5 for severe retinopathy of prematurity. For any stage of retinopathy of prematurity, the sensitivity and specificity of the ROPScores were 98.6% (95% confidence interval = 97.9%-99.3%) and 35.3% (95% confidence interval= 32.3%-38.3%), with a positive predictive value of 76.6% (95% confidence interval= 74.0%-79.2%) and a negative predictive value of 92.3% (95% confidence interval= 90.6%-94.0%). For severe retinopathy of prematurity, the sensitivity was 100% and specificity was 57.3% (95% confidence interval= 54.2%-60.4%), with positive predictive value of 22% (95% confidence interval= 19.4%-24.6%) and negative predictive value of 100%. The cutoff points correctly identified all infants that developed severe retinopathy of prematurity in this cohort. Conclusions: The ROPScore was useful to identify preterm babies at risk for retinopathy of prematurity. In this population, the ROPScore detected all patients at risk for any stage retinopathy of prematurity and severe retinopathy of prematurity. The ROPScore values in this study were similar to those previously described, thereby successfully validating the ROPScore for early detection of retinopathy of prematurity in very low birth weight preterm infants.

RESUMO Objetivos: Avaliar a sensibilidade, especificidade e os valores de pontos de corte do ROPScore, um escore baseado em fatores de risco cumulativos capaz de prever a ocorrência da retinopatia da prematuridade em prematuros de baixo peso no sul do Brasil. Métodos: Estudo retrospectivo por meio de análise de prontuários de todos os prematuros com peso ao nascer ≤1500g e/ou idade gestacional ≤32 semanas selecionados para retinopatia da prematuridade em duas instituições brasileiras entre agosto de 2009 e dezembro de 2015. Resultados: O estudo incluiu 322 pacientes. A média do peso ao nascer foi de 1181,8 ± 292,5 gr e a idade gestacional média foi de 29,5 ± 2,3 semanas. A incidência de retinopatia da prematuridade em qualquer estágio e retinopatia da prematuridade grave foi de 68,3% e 17%, respectivamente. Os valores do ROPScore variaram de 8,7 a 19,9. O melhor ponto de corte para sensibilidade e especificidade foi estabelecido em 11 para retinopatia da prematuridade em qualquer estágio e 14,5 para retinopatia da prematuridade grave. Para retinopatia da prematuridade em qualquer estadiamento, o ROPScore apresentou sensibilidade de 98,6% (95%IC 97,9-99,3) e especificidade de 35,3% (95%IC 32,3-38,3), valor preditivo positivo (VPP) de 76,6% (95%IC 74,0-79,2) e valor preditivo negativo de 92,3% (IC95% 90,6-94,0). Para retinopatia da prematuridade grave, foi registrada sensibilidade de 100%, especificidade de 57,3% (95%IC 54,2-60,4), valor preditivo positivo de 22% (95%IC 19,4-24,6) e valor preditivo negativo de 100%. Os pontos de corte identificaram corretamente todos os pacientes que desenvolveram qualquer estágio ou retinopatia da prematuridade grave no estudo. Conclusão: O ROPScore foi importante para detectar pacientes prematuros com risco de retinopatia da prematuridade. Nesta população, o ROPScore detectou todos os pacientes em risco para qualquer retinopatia da prematuridade em estágio e retinopatia da prematuridade grave. Este estudo mostrou valores semelhantes aos descritos anteriormente, validando com sucesso a ROPScore para detecção precoce de retinopatia da prematuridade em prematuros de muito baixo peso.

Validation of ROPScore to predict retinopathy of prematurity among very low birth weight preterm infants in a southern Brazilian population.

PURPOSES: To evaluate the sensitivity, specificity, and cutoff points for the ROPScore, which is based on cumulative risk factors for the prediction of retinopathy of prematurity (ROP), in a population of very low birth weight (BW) preterm infants in southern Brazil. METHODS: The medical records of all preterm infants with a very low birth weight ≤1,500 g and/or gestational age ≤32 weeks screened for retinopathy of prematurity in two Brazilian institutions between August 2009 and December 2015 were retrospectively reviewed. ROPScores were calculated using birth weight and gestational age, the use of oxygen therapy with mechanical ventilation, and weight gain proportional to birth weight, as measured at postpartum week six and the need for blood transfusions. RESULTS: The study cohort included 322 infants with a mean birth weight of 1181.8 ± 292.5 g and mean gestational age of 29.5 ± 2.3 weeks. The incidences of any stage of retinopathy of prematurity and severe retinopathy of prematurity were 68.3% and 17%, respectively. ROPScore values ranged from 8.7 to 19.9. The best cutoff point for sensitivity and specificity was 11 for any stage of retinopathy of prematurity and 14.5 for severe retinopathy of prematurity. For any stage of retinopathy of prematurity, the sensitivity and specificity of the ROPScores were 98.6% (95% confidence interval = 97.9%-99.3%) and 35.3% (95% confidence interval= 32.3%-38.3%), with a positive predictive value of 76.6% (95% confidence interval= 74.0%-79.2%) and a negative predictive value of 92.3% (95% confidence interval= 90.6%-94.0%). For severe retinopathy of prematurity, the sensitivity was 100% and specificity was 57.3% (95% confidence interval= 54.2%-60.4%), with positive predictive value of 22% (95% confidence interval= 19.4%-24.6%) and negative predictive value of 100%. The cutoff points correctly identified all infants that developed severe retinopathy of prematurity in this cohort. CONCLUSIONS: The ROPScore was useful to identify preterm babies at risk for retinopathy of prematurity. In this population, the ROPScore detected all patients at risk for any stage retinopathy of prematurity and severe retinopathy of prematurity. The ROPScore values in this study were similar to those previously described, thereby successfully validating the ROPScore for early detection of retinopathy of prematurity in very low birth weight preterm infants.

Using the internet to provide information prescriptions.

INTRODUCTION: An information prescription is the provision of specific information to a patient on how to help manage a health problem. The Internet is being used increasingly as a source for information prescriptions, with clinicians directing patients to specific Web sites. As with any health care intervention, patients' lack of compliance is a barrier to the effectiveness of Web-based information prescriptions (WebIPs). WebIPs cannot be helpful if patients do not review the information prescribed for them. OBJECTIVE: The main objective of this study was to quantify the percentage of families who visit a Web site that was specifically prescribed by their physician. In addition, the use of an e-mail reminder was used to determine if it increases the likelihood that families will visit the prescribed Web site. Finally, barriers to accessing the prescribed Web site were identified. METHODS: Children were eligible if they presented to the pediatric gastroenterology clinic with chronic constipation and/or encopresis and their family had an active e-mail account and access to the Internet in their home. During their clinic visit, physicians instructed families to visit a Web site that provided educational information pertinent to their child's problem. Families were given a form with the Web-site address and a log-in identification number. Two days after their clinic visit, half of the families received an e-mail reminding them to visit the Web site. Families were contacted 1 week after their clinic visit to identify barriers to accessing the Web site. RESULTS: Eighty-three families participated in the study. Of the 83 families, 54 (65%) visited the prescribed Web site within 1 week of their clinic visit. Families who received e-mail reminders were significantly more likely to visit the Web site than families who did not receive an e-mail reminder (77% vs 53%). This difference could not be explained by the type or speed of Internet connection or how frequently they accessed the Internet or e-mail. The most common reasons that families cited for not accessing the Web site were "I forgot" and "I didn't have time." Few families cited technical reasons for not accessing the Web site. CONCLUSIONS: Almost two thirds of the families given a WebIP logged on to the prescribed Web site. The probability that families would access the site was increased by 45% with an e-mail reminder. Clearly, e-mail prompts improve compliance to WebIPs. As content and treatment programs continue to proliferate on the Web, it is important to identify barriers and solutions to them to improve overall compliance.