Subretinal injections of viral vectors provide great benefits but have limited cargo capacity; they induce innate and adaptive immune responses, which may cause damage and preclude repeated injections; and they pose administration risks. As a new biotechnology, suprachoroidal injections of biodegradable nanoparticles (NPs) containing a reporter plasmid induce reporter expression in rat photoreceptors and RPE throughout the entire eye and maintain expression for at least 8 months. Multiple injections markedly increase expression. Suprachoroidal injection of NPs containing a VEGF expression plasmid caused severe subretinal neovascularization progressing to subretinal fibrosis, similar to what occurs in untreated patients with neovascular age-related macular degeneration, providing a new model and proof of concept for level and duration of expression. Suprachoroidal injection of NPs containing a VEGF-binding protein expression plasmid significantly suppressed VEGF-induced vascular leakage and neovascularization demonstrating therapeutic potential. These data suggest that nonviral NP suprachoroidal gene transfer may provide a noninvasive, repeatable alternative to subretinal injection of viral vectors.

ObjectiveCases with coronavirus disease 2019 (COVID-19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. MethodsContact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 23, 2020. Patients were confirmed by PCR test. Demographic, clinical and outcomes were collected and analyzed. ResultsOf the 104 patients, 48 (46.15%) were imported cases who were immigrated from Wuhan; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 "generations" was This article is protected by copyright. All rights reserved. Accepted Articleobserved. Five asymptomatic infections were found and 2 of them infected their relatives.Mean age was 43 (rang, 8-84) years and 49 (47.12%) were male. The median incubation period was 6 (rang, 1-32) days, of 8 patients ranged from 18 to 32 days, 96 (92.31%) discharged and 1 (0.96%) died. Average hospital stay was 10 (rang, 8-14) days. ConclusionsFamily but not community transmission occupied the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown wok well.Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID-19. A 14-day quarantine may need to be prolonged.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread worldwide. Methods: This was a retrospective case series involving 218 patients admitted to three tertiary hospitals in the Loudi, Shaoyang, and Xiangtan areas of China from January 21 to June 27, 2020, who were confirmed by RT-PCR to have SARS-CoV-2. The patients' clinical characteristics, laboratory results, treatments, and prognoses based on clinical classification were recorded. Poor outcome was defined as admission to an ICU, the use of mechanical ventilation, or death. Results: The patients were classified into four clinical groups based on disease severity, namely mild (10/218, 5%), moderate (146/218, 67%), severe (24/218, 11%), or critical (14/218, 6%); 24 (11%) asymptomatic cases were also included in the study. The most common symptoms were self-reported cough (162/218, 74%), fever (145/218, 67%), sputum production (99/218, 45%), and fatigue (77/218, 35%). Among the 218 patients, 192 (88%) received lopinavir/ritonavir and interferon-alpha inhalation, and 196 (90%) patients received traditional Chinese medicine. Among the severe and critical patients, 25 (11%) were admitted to an ICU with or without mechanical ventilation, and one patient died. The presence of diabetes [relative risk (RR), 3.0; 95% CI, 1.3-6.8; p = 0.007) or other comorbidities (RR, 5.9; 95% CI, 1.9-17.8; p = 0.002) was independently associated with poor outcome. To date, 20 (9%) patients have retested positive for SARS-CoV-2 RNA after recovering and being discharged. Conclusion: The majority of patients in this case series were clinically classified as having moderate COVID-19. Older patients tended to present with greater levels of clinical severity. The prognosis for patients who were elderly or had diabetes or other chronic comorbidities was relatively poor.

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