Drug Repurposing for COVID-19 Therapy: Pipeline, Current Status and Challenges

Repurposed drugs such as Remdesivir, Fabipiravir and Molnupiravir became life saver drugs during the peak of the COVID-19 pandemic, attesting the efficacy of the repurposing approach. By definition, drug repurposing is the process of identification of new therapeutic use of an existing drug or drug candidate that has already passed the safety, toxicity and pharmacology tests for human use. Although drug repurposing approach involves a significant level of challenge, affordability and faster discovery pipeline outweighs the risks in the event of emergency situations like the current COVID-19 pandemic. In this chapter, we provide a brief summary of the advantages of the drug repurposing approach, followed by an overview of the drug repurposing pipeline and finally end with an update on the status of drug repurposing in developing effective anti-viral therapeutics against COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

Antiviral activity of the human endogenous retrovirus-R envelope protein against SARS-CoV-2

Coronavirus-induced disease-19 (COVID-19), caused by SARS-CoV-2, is still a major global health challenge. Human endogenous retroviruses (HERVs) represent retroviral elements that were integrated into the ancestral human genome. HERVs are important in embryonic development as well as in the manifestation of diseases, including cancer, inflammation, and viral infections. Here, we analyze the expression of several HERVs in SARS-CoV-2-infected cells and observe increased activity of HERV-E, HERV-V, HERV-FRD, HERV-MER34, HERV-W, and HERV-K-HML2. In contrast, the HERV-R envelope is downregulated in cell-based models and PBMCs of COVID-19 patients. Overexpression of HERV-R inhibits SARS-CoV-2 replication, suggesting its antiviral activity. Further analyses demonstrate the role of the extracellular signal-regulated kinase (ERK) in regulating HERV-R antiviral activity. Lastly, our data indicate that the crosstalk between ERK and p38 MAPK controls the synthesis of the HERV-R envelope protein, which in turn modulates SARS-CoV-2 replication. These findings suggest the role of the HERV-R envelope as a prosurvival host factor against SARS-CoV-2 and illustrate a possible advantage of integration and evolutionary maintenance of retroviral elements in the human genome.Copyright © 2023 The Authors.

Risk Factors for Supraventricular Tachycardia among Covid-19 Positive Octogenarians and Potential Outcomes

Background: COVID-19 tends to have a harsher course in the elderly population, which can include the development of arrhythmias, including supraventricular tachycardia (SVT). Due to lack of sufficient data, we studied baseline patient characteristics, comorbidities, and outcomes of SVT in octogenarians admitted with COVID-19, using the 2020 National Inpatient Sample (NIS). Objective(s): We aimed to study the patient characteristics and outcomes of SVT in octogenarians admitted with COVID-19, using the 2020 National Inpatient Sample (NIS). Method(s): Octogenarians (ages 80-89 years, inclusive) with COVID-19 were recruited from the 2020 NIS (April 1st 2020 - December 31st 2020). A diagnosis of SVT was identified via the ICD-10 code "I47. 1". Patient characteristics that can influence the presence of SVT were identified via logistic regression models. The adjusted odds ratios (aOR) having cardiogenic shock or mortality among COVID-19 positive octogenarians with SVT were also explored. Result(s): Our study consisted of 240570 octogenarians who tested positive for COVID-19. 2.2% of them (5250 cases) also had a diagnosis of SVT during their hospitalization. Among them, Females (aOR 0.919, 95%CI 0.868-0.973, p<0.01) were more likely to develop SVT. Racial disparities were also observed as Blacks (aOR 1.234, 95%CI 1.137-1.338, p<0.01) had higher odds of having SVT, whereas Hispanics (aOR 0.898, 95%CI 0.819-0.984, p=0.021) had lower odds compared to Whites. Comorbidities such as chronic pulmonary disease (aOR 1.106, 95%CI 1.037-1.179, p<0.01), and heart failure (aOR 1.122, 95%CI 1.053-1.195, p<0.01) also led to higher odds of SVT. Lower odds were seen among those with diabetes (aOR 0.852, 95%CI 0.802-0.905, p<0.01), obesity (aOR 0.839, 95%CI 0.764-0.921, p<0.01), or smoking history (aOR 0.892, 95%CI 0.835-0.954, p<0.01). The use of mechanical ventilation (aOR 2.829, 95%CI 2.638-3.034, p<0.01) or non-invasive ventilation (aOR 1.755, 95%CI 1.615-1.907, p<0.01) showed higher odds of developing SVT. Finally, patients with SVT had increased risk of cardiogenic shock (aOR 1.510, 95%CI 1.206-1.891, p<0.01) and mortality (aOR 1.166, 95%CI 1.085-1.253, p<0.01). Conclusion(s): Multiple factors influenced the presence of SVT among octogenarians who had COVID-19. SVT in these patients was associated with higher incidences of cardiogenic shock and mortality. Additional focus targeting patient care and further research to better understand the mechanisms behind these variations may help improve outcomes. [Formula presented]Copyright © 2023

Cardiac Arrhythmias among Myocarditis Patients Positive with Covid-19 and Associated Mortality Risk, an Analysis from the 2020 National Inpatient Sample

Background: Viruses are the most common cause of myocarditis. With the ongoing COVID-19 pandemic, several cases of myocarditis have been reported in COVID-19 positive patients. Such patients may also experience a variety of arrhythmias that can provoke death. Objective(s): To evaluate the presence of various cardiac arrhythmias among COVID-19 positive myocarditis patients and understand their impact on mortality. Method(s): COVID-19 positive patients, admitted between April 1st 2020 to December 31st 2020, were recruited from the 2020 National Inpatient Sample. The presence of myocarditis and various cardiac arrhythmias were also identified via their respective ICD-10 codes. Logistic regression models were used to identify the odds of mortality in the presence of myocarditis. We further proceeded to estimate the odds of mortality among myocarditis patients who had various arrhythmias. Result(s): Our study found 6135 (0.4%) patients with myocarditis among 1628110 cases of COVID-19 recorded in the United States between April to December 2020. Age ranged between 0 - 90 years with a mean of 58 years. Multiple cardiac arrhythmias were also observed among myocarditis patients as 310 (5.1%) recorded supraventricular tachycardia, 520 (8.5%) had ventricular tachycardia, 120 (2.0%) had ventricular fibrillation, 520 (8.5%) had paroxysmal atrial fibrillation, 165 (2.7%) had atrial flutter, and 20 (0.3%) had long QT syndrome. The presence of myocarditis was linked with higher odds of mortality among all COVID-19 patients (aOR 2.551, 95% CI 2.405-2.706, p<0.01). Various cardiac arrhythmias were also potential predictors of mortality among myocarditis cases in COVID-19 patients, such as supraventricular tachycardia (aOR 1.346, 95% CI 1.041-1.74, p=0.023), ventricular tachycardia (aOR 1.896, 95% CI 1.557-2.308, p<0.01), ventricular fibrillation (aOR 4.161, 95% CI 2.74-6.319, p<0.01), and atrial flutter (aOR 1.485, 95% CI 1.047-2.106, p=0.026). Conclusion(s): Myocarditis was associated with higher mortality among COVID-19 admissions. Arrhythmias such as supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, and atrial flutter were predictive of higher mortality in these patients. Continued caution is advised among health-care providers encountering these arrhythmias in myocarditis patients who are COVID-19 positive. [Formula presented] French language not detected for EMBFRA articles source xmlCopyright © 2023

Insights into Molecular Evolution and Increased Transmissibility of SARS-CoV-2

The never-ending race for survival between the virus and its host continues to be a major challenge for biologistsas well as healthcare professionals. Owing to their simple genome organization, capacity for replication, mutation and adaptation - viruses can evolve rapidly, thereby posing a constant threat to human and other animal hosts The animal-human species barrier constitutes a considerable hurdle for zoonotic viruses, and often shields humans from the risk of new outbreaks. However, modern lifestyles and advanced technology have diminished geographic barriers, exposing humans to outbreaks initiated in one part of the world, and amplifying the associated health risks and economic losses across the globe. The novel SARS-CoV-2 outbreak that originated from Wuhan, China at the end of 2019 highlights that humans are continuously living under the threat of emerging zoonotic viruses. The Coronavirus disease 2019 (COVID-19) pandemic continues unabated despite theavailability and deployment of multiple approved vaccines and supportive therapies. Moreover, SARS-CoV-2 variants have emerged which contain mutations that promote viral transmissibility and/or virulence. Furthermore, these new variants have raised concerns over the protective efficacy of current vaccines and the susceptibility of unvaccinated individuals. This chapter discusses the potential causes and factors that influence viral fitness and host selection leading to the emergence of easily transmissible and highly pathogenic SARS-CoV-2 variants. © 2023 by World Scientific Publishing Co. Pte. Ltd.

Emergence of a New Zoonotic COVID-19 that Creates a Pandemic: Update on Current Pharmacotherapeutics and Future Prospective of Plasma Therapy

The current decade started on an unexpected note, with almost the entire world grappling with a newly arisen pandemic. A novel coronavirus, tracing its first human host to a Chinese province, has spread to all geographical areas with human populations. The virus, named SARS-CoV-2, infects the lower respiratory tract, much like other coronaviruses, that caused the 2002 epidemic, to which it is eponymous. The severity of infection is seen in individuals with comorbidities like diabetes, cardiovascular disorders, chronic respiratory problems, hypertension, cancer, etc. This virus represents another incidence of zoonosis to humans and has infected over eighteen million people since December 2019, of its first human transmission. All the currently employed therapies are either aimed at alleviating the severity of the symptoms or being administered on a trial basis. This review attempts to summarize brief aetiology of the virus, epidemiology of the outbreak, clinical symptoms of the disease with a postulated mechanism of pathogenesis and several existing and approved drugs and therapeutics along with plasma therapy, which are being clinically reviewed for their activity, as well as safety, against the disease;none of which are approved yet. A few promising vaccine candidates, as per in vivo studies, are also underway, but their evaluation might take a year at least. Meanwhile, experts have come up with the concept of "social distancing" to stem the viral spread, as the medical research fraternity of the world strives hard to find a safe, successful and effective cure for it.Copyright © 2021 Bentham Science Publishers.

Olfactory and taste dysfunction in COVID-19-incidence and recovery

Background: Olfactory and taste dysfunctions have been identified as prominent signs of COVID-19 infection. The data on its prevalence, time of onset, and recovery is highly variable. Objective: The study was aimed at establishing the incidence of and the factors influencing smell and taste disorders in COVID-19-affected patients. Methodology: Telephonic interviews were used to collect data on the symptoms of COVID-19-positive patients, with an emphasis on smell and taste disorders. Patients have severe disease and a history of illnesses that may affect olfaction or taste, and those unwilling to participate were excluded. Results: A total of 1488 COVID-19-positive patients were identified. A total of 772 were included and interviewed, and their data were analysed. A total of 242 (31.3%) patients developed symptoms related to smell and/or taste. Anosmia (149) and ageusia (152) were the most common. Younger patients were more commonly affected (p = 0.0016). The presence and degree of smell symptoms and taste symptoms showed a small positive correlation (r =.234, p <.001). A strong relationship was seen with fever (r =.825, p <.001) and a significantly moderate relationship with breathing difficulty. There was no significant difference based on age or sex for the recovery of smell or taste sensations. There was a significant correlation between taste recovery and smell recovery times (p < 0.00001). Conclusion: Smell and taste disorders, as early clinical symptoms of COVID-19, may have a diagnostic as well as a prognostic value. Treatment protocols for these patients are yet to be defined. A positive association between these symptoms and breathing difficulty was found, and we recommend COVID-19 testing and monitoring of symptoms for all patients with new-onset OTD symptoms. A combination of active enquiry about these symptoms, along with objective testing when the patients present with COVID-19 symptoms may help in better understanding of the pathophysiology and timely initiation of treatment. © 2023, The Author(s).

Effectiveness of Consumer Promotions in Brick-and-Mortar Retail Stores

The purpose of this study is to identify the factors that aid in the measurement of the effectiveness of consumer promotions in brick-and-mortar retail. The already highly competitive landscape of retail is set to undergo a huge transformation post the COVID-19 outbreak, which will inadvertently lead to manufacturing cutting down costs wherever possible to maintain their margins and stay afloat. Advertising spends are bound to go down, and there is a need for a statistical model to measure the effectiveness of the capital spends by a firm towards consumer promotions. For the study, national level sales data of 4 sub-brands of a particular toilet soap brand (shower soap bars) was analyzed for a leading retail chain in India from January 2018 to February 2020. Regression analysis was used to do the data analysis. The study focused on price-off consumer promotions only for the designated period for four variants of a popular Indian soap brand. The discount percentage (including both promotion spend by the manufacturer as well as a retailer), the quantity of the particular unit sold on which the promotion was run during the period when the promotion was run, the effective price to consumer per gram, and profitability for the manufacturer in terms of the net contribution percentage were the factors which were found to show a strong correlation and formed the input variables for the regression equation. The regression analysis showed that all the factors, namely: overall discount percentage, quantity sold, the effective price per gram, and the net contribution (profitability), were statistically significant in determining the uplift in sales quantity due to the discount (the effectiveness of the price promotion). The equation provides retailers and manufacturers a model to measure the effectiveness of promotion spending for price promotions that are run every month at a national and state level by giving state-level values as inputs. It also helps arrive at a baseline sales quantity for a particular SKU if no price-off promotion is run.

Role of Functional Food Additives in Regulating the Immune Response to COVID-19

Background: Food additives act as preventive measures and promote a healthy immune response against pathogenic diseases. There are several functional food additives with antiviral potential that are part of our daily food supplements, which can be exploited to improve the immunity of the human being during the pandemic of COVID-19. Scope and Approach: For this study, an extensive database search using the scientific databases and Google Scholar, as well as commercial search engines, such as Google and Google Patent, was con-ducted to explore commercial and patentable applications. Key Finding: Food additives, such as Phyllanthus emblica, Long pepper, Cinnamon, Turmeric, Cardamom, Ginger, Garlic, Holy Basil, and Liquorice, are used in traditional cultures as preventive treatments. The phytocompounds extracted from these food additives are immune modulators against various pathogenic inflammations. Enhancing the immune response and boosting health are the benefits of these food additives. Conclusion(s): The research literature and reputable sources online confirm that functional food additives in a regular diet may help cure COVID-19 disease. It is necessary to conduct scientific research to determine the effectiveness of food additives. Future Direction: The majority of diseases are caused by metabolic disorders. It is clear that diet plays a major role in controlling the inflammation associated with diseases and metabolic disorders. There is still a lack of phytochemical screening of compounds in food additives and their interaction with me-tabolism. This effort will help the science community to think outside of the box of medicine. Copyright © 2022 Bentham Science Publishers.

Innovation in the Covid-19 Pandemic Using the Inquiry-Based Learning Approach to Improve Active Learning, Confidence, and Critical Thinking of Nursing Students

The use of social media has grown significantly in the last few years. Social media refers to "the websites and online tools that facilitate interactions between users by providing them opportunities to share information, opinions, and interest " (Swar and Hameed, 2017, p. 141). Adolescents have been found to be more vulnerable to addiction and crimes related to social media. Hence, the study has tried to understand the association of social media with the well being of adolescents. The first part of the paper deals with the role and relevance of social media.Further, the literature review depicts a strong connection between social media and individuals' well-being. For the quantitative analysis, various statistical techniques are used. In order to evaluate the association between variables, the composite index has been prepared. Further, the ranking has been given to reflect social media's impact on adolescents' well-being. Lastly, a few recommendations have been made for the state government regarding the well being of the adolescents.

Molecular docking studies on the phytoconstituents as therapeutic leads against SARS-CoV-2

Because of the present pandemic researchers are seeking for phytocandidates that can inhibit or stop SARS-CoV-2. The main protease (Mpro) of SARS-CoV-2 and spike glycoprotein (S) are both suppressed by bioactive compounds found in plants that work by docking them together. The Mpro proteins 6LU7 (complex with an inhibitor N3) and 5C3N (space group C2221) were employed in docking research. PyRx and AutoDock Vina software were used as docking engine. 22 identified phytoconstituents were selected from IMPPAT, a manually curated database, on the basis of their antiviral effects. Docking studies showed that phytoconstituents β-amyrin (-8.4 kcal/mol), withaferin A (-8.3 kcal/mol), oleanolic acid (-7.8 kcal/mol), and patentiflorin A (-8.1 kcal/mol) had the best results against 5C3N Mpro protein whereas kuwanon L (-7.1 kcal/mol), β-amyrin (-6.9 kcal/mol), oleanolic acid (-6.8 kcal/mol), cucurbitacin D (-6.5 kcal/mol), and quercetin (-6.5 kcal/mol) against 6LU7 Mpro protein. All the compounds were examined for their ADMET characteristics using SwissDock. Present research reports that the phytoconstituents along with docking score will be helpful for future drug development against Covid-19. © 2022 Industrial Chemistry Research Institute. All rights reserved.

Deep Learning Artificial Intelligence in Vision-Threatening Disease in Clinical and Community Screenings

Purpose : Age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma are vision-threatening diseases (VTDs) affecting 36 million people in the USA. With 5.7 ophthalmologists per 100,000 Americans, over 50% of VTDs go undetected. We assessed deep learning Artificial Intelligence (DLAI) in VTD detection in community and clinical settings. Methods : 223 subjects (mean age 54.6, 58% male) from community screenings (A) and clinic (B) underwent 45-degree retinal imaging. In A (non-dilated), an onsite telemedicine reader (R1) and remote ophthalmologist (R2) graded image quality (gamma and alignment, 1-5 scale) and referable VTD using the international grading scales for AMD and DR, and cup-to-disc ratio and nerve fiber layer for glaucoma. In B (dilated), gradings were collected from R1 and the clinical diagnosis (d). A senior ophthalmologist (R3) adjudicated disputed findings. In A, DLAI VTD referral was compared to R1/R2/R3 consensus (S);in B, overall referral was compared to R1/d/R3 consensus (C). Images were uploaded to a cloud-based DLAI (SELENA+, EyRIS Pte Ltd) (Fig 1). Cohen's kappa assessed intergrader agreement. Results : R1 and R2 found 4.7% eyes ungradable. DLAI marked 55.6% ungradable;74.6% of them were for AMD. Of the DLAI ungradable eyes, image quality was ≤ 3, and 56.2% had ≥ 1+ cataract (R1). Compared to in A, in B DLAI had higher sensitivity (97.1% vs. 63.2%) and positive predictive value (69.4% vs. 32%). In A, DLAI had higher specificity (94.5% vs.16.7%) and negative predictive value (98.4% vs. 75.0%) (Table 1). In A, Cohen's kappa was 0.946 between R1 and R2, with a 13% disagreement rate. In 56% of the disagreements, R3 agreed with R1. In B, Cohen's kappa was 0.874 for R1 and d;R1 referred more than d. In A and B, DLAI referred more than R1, R2, and H/C. DLAI referred all eyes with > 1 VTD (1%) for further examination. Grading times for DLAI, R1, and R2 were 30, 129, and 68 seconds. Conclusions : DLAI performed best in DR and glaucoma detection;a potential solution for the high ungradable rate can be for DLAI to re-center uploaded images. DLAI can increase efficiency and accessibility of screenings for multiple VTDs, in both underserved populations and clinic. The ability to minimize direct contact confers an advantage during COVID-19. Further studies will investigate DLAI use in VTD progression.

Provision of Reading Glasses During Underserved Community-Based Tele-Ophthalmology Screenings

Purpose : The most common cause of blurry vision in the United States is refractive error. Despite being a correctable condition, over 8.2 million people are estimated to have their refractive error go undiagnosed or untreated. Minorities and low-income groups in particular have significantly increased odds of inadequate correction and double the rates of near-vision impairment. We aimed to address this gap in care through the provision of refractive glasses during community-based tele-ophthalmology screenings. Methods : Eight free eye screening events were held in Newark and West New York, NJ. Demographic information, intraocular pressure, visual acuity, auto-refraction, retinal imaging, and optical coherence tomography were obtained from each subject as part of a comprehensive tele-ophthalmology protocol. Reading glasses were provided as needed based on the recommendation of a certified telemedicine reader. Eligible recipients completed surveys on site regarding access to eye care. They were surveyed again by phone after one month to assess degree of satisfaction and vision improvement. Results : 38 subjects (mean age 53, 47% male) qualified for presbyopia correction and received reading glasses. 97% were Hispanic and 3% were African American. Of the 33 that returned surveys, 88% reported not seeing an eye doctor annually. The most common reason was lack of insurance or inability to pay (71%). Others included having no need to see an eye doctor (10%), disliking eye doctors (7%), not knowing the importance of regular eye exams (3%), and COVID-19 (3%). Of the 25 subjects that were reached for follow-up, 92% reported using the glasses daily. Those that did not reported the power was too strong or they did not feel they needed them. Subjects noted an average improvement in vision of 4.4 out of 5 and an average satisfaction of 4.7 out of 5 (Figure 1). Conclusions : Glasses distribution is an effective way to address refractive error in underserved communities. Given the gaps in knowledge and utilization of eye care identified in our study, there is an obvious need for continued outreach to these areas. Further studies will include larger populations and evaluate mobile refraction devices to increase ease and reach of glasses provision.

Automated Puff Tonometry in Comprehensive Community Based Screening for Vision Threatening Diseases during SARS-CoV-2

Purpose : Over 50% of individuals with vision-threatening disease (VTD) (e.g., diabetic retinopathy, glaucoma, macular degeneration) are unaware of their condition, and once diagnosed, 80% will not follow up for clinical care, especially since the onset of SARS-CoV-2 in 2020. Remote teleophthalmology with real-time robotic teleconsultation was implemented to include automated puff-tonometry (APT) as pre-triage to identify patients who require more detailed clinical assessment and treatment. Methods : 224 subjects (58% male) of average age 55 years were screened over 8 events. Following COVID-19 protocols screenings took place in New Jersey churches and health fairs featuring a high prevalence of African American and Hispanic subjects. Masked and self-reported vaccinated subjects underwent medical history, blood pressure, visual acuity (with pinhole), automated puff-tonometry (APT) for intraocular pressures (IOP), automated refraction, non-mydriatic retinal imaging, optical coherence tomography (OCT), and wearable visual field device (WVFD) testing. Face masks were fitted with surgical tape on the nose bridge to limit instrument fogging. To minimize equipment contact, all subjects were screened in the standing position, including APT and retinal imaging (Fig.1). Chi-square and t-tests were performed to assess factors associated with glaucoma referral. Subjects without IOP readings were excluded;significance was set at p<0.05. Results : 10.29% of measured eyes had an IOP>18 and underwent additional testing including OCT-B of the optic nerve head, nerve fiber layer, and ganglion cell complex. 31.43% of eyes with IOP>18 underwent teleconsultation with a glaucoma specialist, vs. 8.85% of eyes with IOP≤18 ((p<0.001), Table 1). The difference in mean age in subjects with glaucoma referral vs. without (57.42 vs. 51.61 years) was significant (p=0.008). Conclusions : APT was useful in supporting on-site OCT-B imaging and WVFD referral (37.67%, 8.52% of total subjects) that yielded 17.94% referral to on-site teleconsultation through a real-time telerobot. Future investigation will include larger and more diverse community-based populations.

Community Based Eye Screenings Using Retinal and OCT-B Combination Imaging in Glaucoma During COVID-19

Purpose : Retinal imaging is the gold standard in tele-ophthalmology. Limitations in twodimensional imaging can lead to poor triage or unnecessary clinical referrals, especially during COVID-19. Combined retinal imaging with Optical Coherence Tomography-B scan (OCT-B) in detecting vision threatening diseases (VTDs) such as glaucoma in communitybased screenings adds a third dimension to subject data. Methods : A non-mydriatic Topcon 3D Maestro1 imaging system was deployed in this pilot study to screen 120 subjects (43.3% male, mean age 55.1) in community-based screenings. Measurements of vertical cup-to-disc ratio (VCDR), nerve fiber layer (NFL) thickness and macular and ganglion cell layer (GCL) thickness were collected along with color retinal images by the Maestro1. Visual acuity and intraocular pressures (IOP) were obtained as part of the screening protocol. Four types of OCTs were acquired: 78.33% 3D Wide, 13.33% 3D Macula, 5.83% 3D Disc, and 2.51% 5-Line Cross. An on-site certified reader (CR) interpreted results and provided consultation follow-up to a remote ophthalmic subspecialist. Results : Of 222 eyes, OCT-B confirmed follow-up in 86.94%. 88.3% of subjects had referable eye pathology: 23.33% to general or specialty eye clinic and 65% to telemedicine. CR glaucoma referral based on OCT-B scan, VCDR and NFL defects was compared to OCT-B referral based on VCDR ≥0.65. Cohen's kappa was 0.546 with 30% disagreement. Compared to CR, OCT-B generated VCDR had a 91.1% specificity and 42.3% sensitivity in detecting glaucoma. VCDR, IOP, NFL, and GCL measurements were significantly correlated with CR glaucoma referral (p<0.05). Only VCDR, NFL, and GCL were significantly correlated with Maestro 1 glaucoma referral (p<0.05). Conclusions : OCT-B images provide valuable added diagnostic information about referrals in glaucoma. Its ability to capture greater depth of information about the eye, such as NFL and GCL measurements, compared to traditional two-dimensional retinal photography, warrants consideration for OCT-B as a replacement for non-mydriatic retinal photography as the gold standard in ophthalmic diagnostics. Further studies can investigate the utility trend analysis of OCT-B in predicting VTD's progression over time.

Robotic Telepresence Consults in Underserved Community-Based Vision Threatening Disease Screenings During COVID-19

Purpose : Vision Threatening Diseases (VTDs) (age-related macular degeneration, cataracts, diabetic retinopathy, glaucoma) affect 36 million individuals in the United States. 50% are unaware they have a VTD, disproportionally affecting minorities and lowincome groups with less access to eye care. While screening programs in underserved communities result in early detection, less than half of subjects with findings follow up with a specialist. This number is four times lower during COVID-19. Methods : Robotic Telepresence (RT) was implemented in this pilot study during COVID19 to increase real-time access to specialist care. 58 subjects (age 56, 45% male) underwent a non-mydriatic screening protocol over five screenings. They were divided into three groups for consult: In Person (IP) followed by RT (N = 21), RT followed by IP (N = 19), and IP only (N = 18). IP consult was done by an on-site certified reader. RT consult was done by an off-site glaucoma or retina specialist with access to blood pressure, visual acuity, intraocular pressure, 45° retinal images, and ocular coherence tomography Bscans via cloud-based software. Video connection for RT was established via HIPAAcompliant mobile hotspot. Subject demographics and preferences were collected afterwards via survey. Results : Of 40 RT consults, 26 were second opinion for VTD suspect and 14 were wellness encounters. 24 reported their last eye care visit >3 years ago or never. Following RT consult, 18 subjects received one or multiple VTD diagnosis and 3 with glaucoma were referred for pressure-lowering eye drops. In the group with IP consult first, preferences were 5% RT, 52% IP, and 43% none. In the group with RT consult first, preferences were 5% RT, 58% IP, and 37% none. There was no significant difference in number of questions asked, wait time, or encounter length between IP and RT consults. Conclusions : RT consults proved valuable in community-based VTD screenings, particularly during COVID-19 when access to eye care is further limited. Most subjects preferred IP. However subjects with VTD that face socioeconomic barriers benefit from immediate RT consult and management directives from remote subspecialists. Further studies should incorporate consults from additional specialties (endocrinologists, general practitioners, social workers) and include telehealth CPT code for reimbursement.

Agreeability of Tele-ophthalmology and Artificial Intelligence-Based Diagnosis of Diabetic Retinopathy

Purpose : The COVID-19 pandemic exposed the need for increased mobilization of teleophthalmology resources. Artificial intelligence (AI) may serve as a tool to assist physicians in triaging highest need patients if the AI's assessment of disease is comparable to the physician's assessment. This study assesses the ability of AI software to diagnose diabetic retinopathy (DR) as compared to Tele-ophthalmology and in-person examination by a retina specialist. Methods : Records of forty patients (average age 55.1±10.9 years) presenting to an urban retina clinic were reviewed retrospectively for factors including demographics, retinal photos taken by Canon CR-2 Plus AF Retinal Imaging camera (Tokyo, Japan), and diagnosis of DR based on the International Clinical Diabetic Retinopathy (ICDR) classification scale during an in-person clinic visit in which a fundus exam was performed. Retinal photos were graded by AI software, EyeArt (EyeNuk, CA), as Normal, Mild DR, or More than Mild DR. Retinal images were also graded remotely by a retina specialist using the ICDR classification scale via TeamViewer software (Tele). Agreement between Tele, AI, and inperson DR diagnosis was assessed using Cohen's Kappa (κ) coefficient using IBM® SPSS® Statistics software. Results : Among 80 eyes, 33 were diagnosed in-person with no DR, 5 with mild nonproliferative DR (NPDR), 9 with moderate NPDR, 3 with severe NPDR, 7 with proliferative diabetic retinopathy (PDR), and 23 with regressed PDR. Eleven and 26 eyes could not be graded by Tele or AI, respectively. κ±SE for in-Person diagnosis vs Tele was 0.859±0.058 (p<.001), in-person vs AI was 0.751±0.082 (p<.001), and Tele vs AI was 0.883±0.063 (p<.001). Conclusions : AI is a reliable tool for screening patients for DR and referring them for physician evaluation since AI had a substantial rate of agreement with the in-person diagnosis and near perfect agreement with Tele. Tele grading was in near perfect agreement with the in-person diagnosis, showing that Tele is a reliable option for a physician to remotely screen patients that may be ungradable by AI. However, improvements are needed due to the high number of images that are ungradable via Tele and AI. Further studies should assess ways to reduce the number of ungradable images via Tele and AI and create a trend analysis for multiple visits for a given patient.

Telemedicine Vision Threatening Diseases and Wellness Screenings in Uninsured Latino Community During COVID-19

Purpose : Limited access to eye-care among Latinos can lead to missed Vision Threatening Diseases (VTDs) defined as Age-related Macular Degeneration (AMD), cataracts, Diabetic Retinopathy (DR) and glaucoma. As 50% of the people with VTD's are unaware of their condition made worse during COVID-19, comprehensive eye screenings to assess ocular wellness was implemented using telemedicine, Artificial Intelligence (AI) and robotic consultations. Methods : State-sponsored screenings were conducted at a church in West New York, NJ (78% Latino, mostly from Colombia) over 3 weekends during the 2021 Pandemic. All participants had received two-dose vaccinations and wore a surgical mask during screenings. Nine first-year medical students and 6 community volunteers took part in the wellness evaluation including: medical history, blood pressure, visual acuity, automated refraction, puff tonometry, 45-degree non-mydriatic retinal photography AI. To confirm findings: 6-micron resolution ocular coherence tomography (OCT) B-scan was performed. Screened subjects had their data reviewed by an onsite ophthalmic grader using a Spanish-speaking interpreter. As 80% of screened subjects are lost to follow-up, remote robotic ophthalmology consultation via HIPAA compliant Wi-Fi was utilized in real-time to connect with an off-site ophthalmologist. Results : 153 subjects, (71 Female (46%), median age 55) had 127 ocular findings (Table 1) found in 85 (55%) subjects, of which 98% of findings were previously unknown and 40 (47%) classified as VTD. 23(15%) subjects had multiple findings. OCT confirmed 23 cases of AMD and glaucoma. AI referred 39 cases. 36 individuals took part in robotic virtual consults. Findings were: cataracts 70 (45%), glaucoma 32 (20%), and AMD 25(16%). Among those with findings, 82% were uninsured and 90% had >2 years since last eye exam. 32 (32/153) subjects had undertreated or untreated hypertension. 93% were un-familiar with telemedicine. Conclusions : Latinos without health insurance and ease of access to eyecare may have a higher burden of multi-VTDs. An exception was DR which could be a limitation of population bias. This pilot study supports comprehensive wellness eye screenings that may allow for early detection, confirmation, and referral of single or multiple VTD in high-risk low-income communities. Further studies are needed using larger sample populations. (Figure Presented).

Virtual Reality Visual Field Exam in Community Screenings During COVID-19

Purpose : 57.5 million people worldwide are affected by glaucoma. However, 50% of those with glaucoma are unaware, and 80% of those identified for follow-up in community screenings (CS) fail to do so. Current standards of visual field testing are usually limited to the clinic. As such, a wearable perimetry headset was used to perform Virtual Reality Visual Field Acuity (VRVFA) examination for suspected visual field loss in the community minimizing exposure to COVID-19 and the need for follow-up. Methods : 31 subjects from 4 CS were screened by an onsite certified telemedicine reader (CR) who considered family history, visual acuity, intraocular pressures, cup-to-disc ratio, nerve fiber layer defects, and ganglion cell complex captured by non-mydriatic photography and ocular coherence tomography (OCT-B). Cataracts were also graded. Supervised VRVFA testing with a multilingual Palmscan VF2000 Analyzer (Fig.1) was performed in 6 minutes on average. Eyes with fixation losses >20% or false positive/negative ratios >0.375 were excluded. Visual field index (VFI), mean deviation (MD), pattern standard deviation (PSD), and mean sensitivity (MS) from VRVFA were compared to CR glaucoma referral and cataract grading. Descriptive statistics, independent samples t-tests, and Mood's median tests were performed. Subjects with positive findings underwent same-day robotic glaucoma specialist telepresence evaluation. Results : 37 eyes from 31 subjects met inclusion criteria (mean age 51.42 ± 14.57 years, 56.76% male, 94.59% Hispanic). 7 (18.92%) eyes were referred for glaucoma evaluation. Glaucoma referrals had significantly different VFI (66.86% vs 86.40%, p=0.027), MD (-9.60 vs -4.04, p=0.031), and MS (19.94 vs 26.01, p=0.027) (Fig. 2). 30 (81.08%) eyes were 0-1+ in cataract grading, 5 (13.51%) were 2-3+, and 2 (5.41%) were intra-ocular lenses (IOL);respectively, these subgroups were not significantly different in VFI (84.20% vs 92.80% vs 35.00%, p=0.147), MD (-4.70 vs -2.11 vs -18.41, p=0.147), PSD (3.52 vs 2.25 vs 9.69, p=0.053), or MS (25.38 vs 27.75 vs 9.91, p=0.147) (Fig. 2). Conclusions : VRVFA testing yielded valuable information on the extent of vision loss as a supportive screening tool for glaucoma congruent with referrals. Expanded testing is needed. Future studies may evaluate VRVFA utility in evaluating other peripheral vision threatening diseases.

Capsule Networks with Chest X-Ray Enhancement for Detection of COVID-19

Corona virus was declared a global pandemic that has affected people worldwide. It is critical to diagnose corona virus-infected individuals to restrict the virus's transmission. Recent research indicates that radiological methods provide valuable information in identifying infection using deep learning algorithms. Deep learning has contributed to large-scale medical data research, providing new ways and chances for diagnostic tools. This research attempted to investigate how the Capsule Networks leverage chest X-ray scans to identify the infected person. We suggest Capsule Networks identify the illness using chest X-ray data. The proposed approach is rapid and robust, classifying scans into COVID-19, No Findings, or any other issue in the lungs. The study can be used as a preliminary diagnosis by medical practitioners, and the study focuses on the COVID-19 class, a minority class in all public data sets accessible, and ensures that no COVID-19 infected individual is identified as Normal. Even with a small dataset, the model provides 96.37% accuracy for COVID-19 and for the non-COVID-19, and on multi-class classification, it provides an accuracy of 95.12%. © 2022 IEEE.