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MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    The Writing On The Wall Intravitreal Injection Compliance During The COVID-19 Pandemic and Its Foreseeable Consequences

    Authors: Lauren M Wasser; Yishay Weill; Koby Brosh; Itay Magal; Michael Potter; Israel Strassman; Evgeny Gelman; Meni Koslowsky; David Zadok; Joel Hanhart

    doi:10.21203/rs.3.rs-53248/v1 Date: 2020-08-04 Source: ResearchSquare

    Background: Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents have become the most prevalent intraocular procedure as they represent the major therapeutic modality for prevalent retinal conditions such as age TRANS-related macular degeneration MESHD macular degeneration HP (AMD) and diabetic retinopathy MESHD retinopathy HP. Effective therapy requires adherence to a schedule of iterative IVI as well as routine clinic appointments. The ongoing Coronavirus disease MESHD 2019 (COVID-19) pandemic has resulted in the reduction of attendance at scheduled clinics visits and IVI. In this study we attempted to analyze the effect of COVID-19 on compliance with anti-VEGF therapy.Methods: A total of 636 eyes received injections during a four-week period of the COVID-19 outbreak in the Retina Clinic. The number of clinic visits for IVI during one month from March 15 to April 14 of 2020 was compared to the similar time period in each of the last four years.Results: The study demonstrates a decrease in clinic visits for IVI when compared with the same four-week interval in the four previous years. Based on the trend of the previous four years, 10.2% of the year’s total was expected for this time period. Using this model, the 636 reported number of injections for the March-April, 2020 period was ~ 5%. This represents a decrease of ~50% of the expected IVI for this time period.Conclusion: The COVID-19 outbreak in Israel severely impacted compliance with anti-VEGF treatments.

    Estimating excess visual loss HP in people with neovascular age TRANS-related macular degeneration MESHD macular degeneration HP during the COVID-19 pandemic

    Authors: Darren S Thomas; Alasdair Warwick; Abraham Olvera-Barrios; Catherine Egan; Roy Schwartz; Sudeshna Patra; Haralabos Eleftheriadis; Anthony P Khawaja; Andrew Lotery; Philipp L Mueller; Robin Hamilton; Ella Preston; Paul Taylor; Adnan Tufail; - UK EMR Users Group

    doi:10.1101/2020.06.02.20120642 Date: 2020-06-05 Source: medRxiv

    Objectives: To report the reduction in new neovascular age TRANS-related macular degeneration MESHD macular degeneration HP (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at one year. Design: Retrospective clinical audit and simulation model. Setting: Multiple UK NHS ophthalmology centres. Participants: Data on the reduction in new nAMD referrals was obtained from four NHS Trusts in England comparing April 2020 to April 2019. To estimate the potential impact on one-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20,825 nAMD eyes from 27 NHS Trusts. Main outcome measures: Simulated mean visual acuity and proportions of eyes with vision [≤]6/60, [≤]6/24 and [≥]6/12 at one year under four hypothetical scenarios: no treatment delay, 3, 6 and 9-month treatment delays. Estimated additional number of eyes with vision [≤]6/60 at one year nationally. Results: The number of nAMD referrals at four major eye treatment hospital groups based in England dropped on average by 72% (range 65 to 87%) in April 2020 compared to April 2019. Simulated one-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision [≤]6/60 from 15.5% (13.2 to 17.9) to 23.3% (20.7 to25.9), and a decrease in the proportion of eyes with vision [≥]6/12 (driving vision) from 35.1% (32.1 to 38.1) to 26.4% (23.8 to29.2). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level at the national level for only one month, these simulated results suggest an additional 186-365 eyes with vision [≤]6/60 at one-year with even a short treatment delay. Conclusions: We report a large decrease in nAMD referrals during the first month of COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision [≤]6/60 and 25% relative decrease in the number of eyes with driving vision at one year.

    Identification of Immune complement function as a determinant of adverse SARS-CoV-2 infection MESHD outcome

    Authors: Vijendra Ramlall; Phyllis Thangaraj; Cem Meydan; Jonathan Foox; Daniel Butler; Ben May; Jessica de Freitas; Benjamin S Glicksberg; Christopher Mason; Nicholas P Tatonetti; Sagi D Shapira

    doi:10.1101/2020.05.05.20092452 Date: 2020-05-13 Source: medRxiv

    Understanding the pathophysiology of SARS-CoV-2 infection MESHD is critical for therapeutics and public health intervention strategies. Viral-host interactions can guide discovery of regulators of disease MESHD outcomes, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of the coronavirus proteome. To determine if conditions associated with dysregulation of the complement or coagulation systems impact adverse clinical outcomes, we performed a retrospective observational study of 11,116 patients who presented with suspected SARS-CoV-2 infection MESHD. We found that history of macular degeneration MESHD macular degeneration HP (a proxy for complement activation disorders) and history of coagulation disorders ( thrombocytopenia MESHD thrombocytopenia HP, thrombosis MESHD, and hemorrhage MESHD) are risk factors for morbidity and mortality in SARS-CoV-2 infected patients - effects that could not be explained by age TRANS, sex, or history of smoking. Further, transcriptional profiling of nasopharyngeal (NP) swabs from 650 control and SARS-CoV-2 infected patients demonstrated that in addition to innate Type-I interferon and IL-6 dependent inflammatory immune responses, infection MESHD results in robust engagement and activation of the complement and coagulation pathways. Finally, we conducted a candidate driven genetic association study of severe SARS-CoV-2 disease MESHD. Among the findings, our scan identified putative complement and coagulation associated loci including missense, eQTL and sQTL variants of critical regulators of the complement and coagulation cascades. In addition to providing evidence that complement function modulates SARS-CoV-2 infection MESHD outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multi-modal analytical approach, combining molecular information from virus protein structure-function analysis with clinical informatics, transcriptomics, and genomics to reveal determinants and predictors of immunity, susceptibility, and clinical outcome associated with infection MESHD.

    Identification of Immune complement function as a determinant of adverse SARS-CoV-2 infection MESHD outcome

    Authors: Vijendra Ramlall; Phyllis M. Thangara; Nicholas P. Tatonetti; Sagi D. Shapira

    doi:10.21203/rs.3.rs-26451/v1 Date: 2020-05-01 Source: ResearchSquare

    Understanding the pathophysiology of SARS-CoV-2 infection MESHD is critical for therapeutics and public health intervention strategies. Viral-host interactions can guide discovery of regulators of disease MESHD outcomes, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of the coronavirus proteome. To determine if conditions associated with dysregulation of the complement or coagulation systems impact adverse clinical outcomes associated with SARS-CoV-2 infection MESHD, we performed a retrospective observational study of 11,116 patients suspected of SARS-CoV-2 infection MESHD. We found that history of macular degeneration MESHD macular degeneration HP (a proxy for complement activation disorders) and history of coagulation disorders ( thrombocytopenia MESHD thrombocytopenia HP, thrombosis MESHD, and hemorrhage MESHD) are risk factors for morbidity and mortality in SARS-CoV-2 infected patients – effects that could not be explained by age TRANS or sex. In addition, using data from the UK Biobank, we implemented a candidate driven approach to evaluate linkage between severe SARS-CoV-2 disease MESHD and genetic variation associated with complement and coagulation pathways. Among our findings, our scan identified an eQTL for CD55 (a negative regulator of complement activation) and SNPs in Complement Factor H (CFH) and Complement Component 4 Binding Protein Alpha (C4BPA), which play central roles in complement activation and innate immunity and were previously linked to Age TRANS Related Macular Degeneration MESHD Macular Degeneration HP (AMD) in a Genome-Wide Association Study (GWAS). In addition to providing evidence that complement function modulates SARS-CoV-2 infection MESHD outcome, the data point to several putative genetic markers of susceptibility. The results highlight the value of using a multi-modal analytical approach, combining molecular information from virus protein structure-function analysis with clinical informatics and genomics to reveal determinants and predictors of immunity, susceptibility, and clinical outcome associated with infection MESHD.

    How urgent do intravitreal anti-VEGF injections need to be to justify the risk of transmitting COVID-19? Proof-of-concept calculations to determine the Health Adjusted Life-Year (HALY) trade-off.

    Authors: Matt James Boyd; Daniel Andrew Richard Scott; David Michael Squirrell; Graham Ashley Wilson

    doi:10.1101/2020.04.27.20075085 Date: 2020-05-01 Source: medRxiv

    Background: Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease MESHD transmission TRANS. Method: We performed probability calculations to estimate COVID-19 infection MESHD status and likelihood of disease MESHD transmission TRANS among neovascular age TRANS-related macular degeneration MESHD macular degeneration HP patients and health care workers during anti-VEGF procedures, at various community prevalence SERO levels of COVID-19. We then applied the expected burden of COVID-19 illness and death MESHD expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease MESHD burden of severe visual impairment HP if sight protecting anti-VEGF injections were not performed. Results: Our calculations estimate for a single treatment, where the background rate of COVID-19 in the community is 1000 active cases per million population, and full personal protective equipment (PPE) is available, that the benefits of treatment are greater than the expected harms to the patient and immediate health care team, provided the probability of severe visual impairment HP without treatment is >0.001%. Without effective PPE, and with a COVID-19 prevalence SERO of 200,000 per million, an 8.5% chance of severe visual impairment HP could still justify monthly injections for six months. Conclusion: In most cases analysed, the reduced disease MESHD burden from avoiding visual impairment HP outweighs the expected HALYs lost from COVID-19 transmission TRANS. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment HP for 5 years are equivalent to nearly 400 moderate cases of infectious disease MESHD lasting 2 weeks each.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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