Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Major depressive disorder (MDD) is a global problem for which current pharmacotherapies are not completely effective. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has long been associated with MDD; however, the value of assessing cortisol as a biological benchmark of the pathophysiology or treatment of MDD is still debated. In this review, we critically evaluate the relationship between HPA axis dysfunction and cortisol level in relation to MDD subtype, stress, gender and treatment regime, as well as in rodent models. We find that an elevated cortisol response to stress is associated with acute and severe, but not mild or atypical, forms of MDD. Furthermore, the increased incidence of MDD in females is associated with greater cortisol response variability rather than higher baseline levels of cortisol. Despite almost all current MDD treatments influencing cortisol levels, we could find no convincing relationship between cortisol level and therapeutic response in either a clinical or preclinical setting. Thus, we argue that the absolute level of cortisol is unreliable for predicting the efficacy of antidepressant treatment. We propose that future preclinical models should reliably produce exaggerated HPA axis responses to acute or chronic stress a priori, which may, or may not, alter baseline cortisol levels, while also modelling the core symptoms of MDD that can be targeted for reversal. Combining genetic and environmental risk factors in such a model, together with the interrogation of the resultant molecular, cellular, and behavioral changes, promises a new mechanistic understanding of MDD and focused therapeutic strategies.

Background A high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance. Methods We performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1–4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results. Results The mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillation (1.0%), and newly detected left ventricular systolic dysfunction with elevated NT-proBNP level (1.0%). Significant sinus bradycardia with heart rate below 50 bpm was detected in 7.2% COVID-19 survivors, which appeared to be self-limiting and recovered over time. For COVID-19 survivors with persistent elevation of troponin level after discharge or newly detected T wave abnormality, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction. Conclusion Cardiac abnormality is common amongst COVID-survivors with mild disease, which is mostly self-limiting. Nonetheless, cardiac surveillance in form of ECG and/or serum biomarkers may be advisable to detect more severe cardiac involvement including atrial fibrillation and left ventricular dysfunction.

IntroductionThere is an outbreak of COVID-19 worldwide. As there is no effective therapy or vaccine yet, rigorous implementation of traditional public health measures such as isolation and quarantine remains the most effective tool to control the outbreak. When an asymptomatic individual with COVID-19 exposure is being quarantined, it is necessary to perform temperature and symptom surveillance. As such surveillance is intermittent in nature and highly dependent on self-discipline, it has limited effectiveness. Advances in biosensor technologies made it possible to continuously monitor physiological parameters using wearable biosensors with a variety of form factors.ObjectiveTo explore the potential of using wearable biosensors to continuously monitor multidimensional physiological parameters for early detection of COVID-19 clinical progression.MethodThis randomised controlled open-labelled trial will involve 200–1000 asymptomatic subjects with close COVID-19 contact under mandatory quarantine at designated facilities in Hong Kong. Subjects will be randomised to receive a remote monitoring strategy (intervention group) or standard strategy (control group) in a 1:1 ratio during the 14 day-quarantine period. In addition to fever and symptom surveillance in the control group, subjects in the intervention group will wear wearable biosensors on their arms to continuously monitor skin temperature, respiratory rate, blood pressure, pulse rate, blood oxygen saturation and daily activities. These physiological parameters will be transferred in real time to a smartphone application called Biovitals Sentinel. These data will then be processed using a cloud-based multivariate physiology analytics engine called Biovitals to detect subtle physiological changes. The results will be displayed on a web-based dashboard for clinicians’ review. The primary outcome is the time to diagnosis of COVID-19.Ethics and disseminationEthical approval has been obtained from institutional review boards at the study sites. Results will be published in peer-reviewed journals.

Objective To identify clinical characteristics associated with the presence of epiretinal membrane (ERM) in patients with uveitis Design Case-control study Participants and Controls 598 subjects seen in a single tertiary referral clinic between January 1, 2008 and December 31, 2011 who were diagnosed with uveitis. Methods Spectral domain optical coherence tomography (SD-OCT) images of all subjects were reviewed to assess for ERM. A multivariate logistic regression analysis was performed to compare characteristics of subjects with ERM (cases) to characteristics of subjects without ERM (controls). A second multivariate analysis assessed the relationship between ERM and visual acuity. Fundus photos were reviewed to compare SD-OCT ascertainment of ERM with photographic ascertainment. Main Outcome Measure Presence or absence of ERM on OCT imaging. Results Of 598 uveitic participants, 246 (41%) were found to have ERM in at least one eye on SD-OCT imaging. The prevalence of ERM by Standardization of Uveitis Nomenclature (SUN) anatomic subtype was 28.1% for anterior uveitis, 57.0% for intermediate uveitis, and 43.4% for posterior and panuveitis. Multivariate analysis showed that the following clinical factors were significantly associated with ERM: older age (3% increased risk per year of age; 95% confidence interval [CI] 1.02-1.05), intermediate uveitis (OR 3.41; 95% CI 1.67-6.96) and posterior and panuveitis (OR 1.81; 95% CI 1.09-3.01), male sex (OR 1.59; 95% CI 1.05-2.42), and history of cataract surgery (OR 1.78; 95% CI 1.13-2.79). When adjusted for covariates, eyes with ERM had a mean logMAR acuity of 0.58 (20/76) versus 0.48 (20/60) in non-ERM eyes (P=0.039). Thirty-eight percent of OCT-defined ERMs in this cohort were not detectable on fundus photos. Conclusions ERM is a common complication of uveitis that is associated with patient age, intermediate, posterior, and panuveitis, male sex, and previous cataract surgery. It can independently contribute to vision loss in uveitic eyes. OCT is more sensitive than fundus photography for identification of ERM in uveitis.

itreoretinal lymphomas (VRL) are rare diseases. They comprise about 1% to 3% of intraocular tumors and the incidence varies between 0.02 to 0.05 of 100 000 people in the North American population. 1 In almost 90% of cases, VRLs are diffuse large B cell lymphomas (DLBCLs) and are considered to be a subtype of the primary DLBCLs of the central nervous system (CNS). Sixteen percent to 34% of patients with VRL have CNS involvement at the time of diagnosis and 35% to 90% will develop CNS lymphoma during the course of their disease. Conversely, 15% to 25% of patients with CNS lymphoma develop VRL. 2,3 Optical coherence tomography (OCT) is an important noninvasive diagnostic tool in diagnosing and managing retinal diseases. In VRL, most of the morphologic features that are seen on OCT are nonspecific. 4-6 The aim of this study was to describe an OCT feature in patients with confirmed VRL. Methods We conducted a retrospective medical record review of patients who received a diagnosis of VRL at the Department of Ophthalmology at Northwestern University. The protocol was approved by the institutional ethics committee, who waived patient consent, and adhered to the Declaration of Helsinki. Patients who had a diagnosis of intraocular lymphoma who were seen by 2 senior attending physicians (D.A.G. and L.M.J.) between July 2014 and January 2018 were identified using a search of electronic medical records. Patient records and all imaging modalities that were carried out at the initial visit and subsequent visits were collected and reviewed for completeness and consistency. The exclusion criteria were an uncertain diagnosis and inadequate OCT image quality. Optical co-IMPORTANCE Vitreoretinal lymphoma is a diagnostic challenge and the pathophysiology is still unclear. OBJECTIVE To describe an imaging finding seen on optical coherence tomography (OCT) of patients with vitreoretinal lymphoma. DESIGN, SETTING, AND PARTICIPANTS This case series study was a retrospective medical record review of patients who received a diagnosis of vitreoretinal lymphoma at the

Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).

Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 case reports, observational studies and the COVID-19 Treatment Guideline issued by the China's National Health Commission (7th edition published March 3rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.