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Importance: Obesity is associated with increased severity of COVID-19. Whether obesity is associated with an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among pediatric populations, independent of its association with acute infection severity, is unclear., Objective: To quantify the association of body mass index (BMI) status before SARS-CoV-2 infection with pediatric PASC risk, controlling for acute infection severity., Design, Setting, and Participants: This retrospective cohort study occurred at 26 US children's hospitals from March 2020 to May 2023 with a minimum follow-up of 179 days. Eligible participants included children and young adults aged 5 to 20 years with SARS-CoV-2 infection. Data analysis was conducted from October 2023 to January 2024., Exposures: BMI status assessed within 18 months before infection; the measure closest to the index date was selected. The BMI categories included healthy weight (≥5th to <85th percentile for those aged 5-19 years or ≥18.5 to <25 for those aged >19 years), overweight (≥85th to <95th percentile for those aged 5-19 years or ≥25 to <30 for for those aged >19 years), obesity (≥95th percentile to <120% of the 95th percentile for for those aged 5-19 years or ≥30 to <40 for those aged >19 years), and severe obesity (≥120% of the 95th percentile for those aged 5-19 years or ≥40 for those aged >19 years)., Main Outcomes and Measures: To identify PASC, a diagnostic code specific for post-COVID-19 conditions was used and a second approach used clusters of symptoms and conditions that constitute the PASC phenotype. Relative risk (RR) for the association of BMI with PASC was quantified by Poisson regression models, adjusting for sociodemographic, acute COVID severity, and other clinical factors., Results: A total of 172 136 participants (mean [SD] age at BMI assessment 12.6 [4.4] years; mean [SD] age at cohort entry, 13.1 [4.4] years; 90 187 female [52.4%]) were included. Compared with participants with healthy weight, those with obesity had a 25.4% increased risk of PASC (RR, 1.25; 95% CI, 1.06-1.48) and those with severe obesity had a 42.1% increased risk of PASC (RR, 1.42; 95% CI, 1.25-1.61) when identified using the diagnostic code. Compared with those with healthy weight, there was an increased risk for any occurrences of PASC symptoms and conditions among those with obesity (RR, 1.11; 95% CI, 1.06-1.15) and severe obesity (RR, 1.17; 95% CI, 1.14-1.21), and the association held when assessing total incident occurrences among those with overweight (RR, 1.05; 95% CI, 1.00-1.11), obesity (RR, 1.13; 95% CI, 1.09-1.19), and severe obesity (RR, 1.18; 95% CI, 1.14-1.22)., Conclusions and Relevance: In this cohort study, elevated BMI was associated with a significantly increased PASC risk in a dose-dependent manner, highlighting the need for targeted care to prevent chronic conditions in at-risk children and young adults.

Competing Interests: Declaration of Competing Interest None.

UVA-EpiHiper is a national scale agent-based model to support the US COVID-19 Scenario Modeling Hub (SMH). UVA-EpiHiper uses a detailed representation of the underlying social contact network along with data measured during the course of the pandemic to initialize and calibrate the model. In this paper, we study the role of heterogeneity on model complexity and resulting epidemic dynamics using UVA-EpiHiper. We discuss various sources of heterogeneity that we encounter in the use of UVA-EpiHiper to support modeling and analysis of epidemic dynamics under various scenarios. We also discuss how this affects model complexity and computational complexity of the corresponding simulations. Using round 13 of the SMH as an example, we discuss how UVA-EpiHiper was initialized and calibrated. We then discuss how the detailed output produced by UVA-EpiHiper can be analyzed to obtain interesting insights. We find that despite the complexity in the model, the software, and the computation incurred to an agent-based model in scenario modeling, it is capable of capturing various heterogeneities of real-world systems, especially those in networks and behaviors, and enables analyzing heterogeneities in epidemiological outcomes between different demographic, geographic, and social cohorts. In applying UVA-EpiHiper to round 13 scenario modeling, we find that disease outcomes are different between and within states, and between demographic groups, which can be attributed to heterogeneities in population demographics, network structures, and initial immunity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nearly six million people worldwide have died from the coronavirus disease (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although COVID-19 vaccines are largely successful in reducing the severity of the disease and deaths, the decline in vaccine-induced immunity over time and the continuing emergence of new viral variants or mutations underscore the need for an alternative strategy for developing broad-spectrum host-mediated therapeutics against SARS-CoV-2. A key feature of severe COVID-19 is dysregulated innate immune signaling, culminating in a high expression of numerous pro-inflammatory cytokines and chemokines and a lack of antiviral interferons (IFNs), particularly type I (alpha and beta) and type III (lambda). As a natural host defense, the myeloid differentiation primary response protein, MyD88, plays pivotal roles in innate and acquired immune responses via the signal transduction pathways of Toll-like receptors (TLRs), a type of pathogen recognition receptors (PRRs). However, recent studies have highlighted that infection with viruses upregulates MyD88 expression and impairs the host antiviral response by negatively regulating type I IFN. Galectin-3 (Gal3), another key player in viral infections, has been shown to modulate the host immune response by regulating viral entry and activating TLRs, the NLRP3 inflammasome, and NF-κB, resulting in the release of pro-inflammatory cytokines and contributing to the overall inflammatory response, the so-called "cytokine storm". These studies suggest that the specific inhibition of MyD88 and Gal3 could be a promising therapy for COVID-19. This review presents future directions for MyD88- and Gal3-targeted antiviral drug discovery, highlighting the potential to restore host immunity in SARS-CoV-2 infections.

In April 2024, in a class action suit for compensation to families of persons suffering injury or death after vaccination with AstraZeneca's (AZ) Covid-19 vaccine [1], the manufacturer admitted in a UK court that the Oxford-AZ Covid-19 vaccine could cause a rare and potentially fatal blood clotting disorder ("thrombosis with thrombocytopenia syndrome" or TTS, which when triggered by a vaccine is called "vaccine induced thrombocytopenia and thrombosis, or VITT) [2]. The AZ Covid-19 vaccine is a chimpanzee adenovirus vectored vaccine encoding the SARS-CoV2 spike protein (ChAdOx1-S) marketed under the names Covishield and Vaxzevria.

Across many fields, scenario modeling has become an important tool for exploring long-term projections and how they might depend on potential interventions and critical uncertainties, with relevance to both decision makers and scientists. In the past decade, and especially during the COVID-19 pandemic, the field of epidemiology has seen substantial growth in the use of scenario projections. Multiple scenarios are often projected at the same time, allowing important comparisons that can guide the choice of intervention, the prioritization of research topics, or public communication. The design of the scenarios is central to their ability to inform important questions. In this paper, we draw on the fields of decision analysis and statistical design of experiments to propose a framework for scenario design in epidemiology, with relevance also to other fields. We identify six different fundamental purposes for scenario designs (decision making, sensitivity analysis, situational awareness, horizon scanning, forecasting, and value of information) and discuss how those purposes guide the structure of scenarios. We discuss other aspects of the content and process of scenario design, broadly for all settings and specifically for multi-model ensemble projections. As an illustrative case study, we examine the first 17 rounds of scenarios from the U.S. COVID-19 Scenario Modeling Hub, then reflect on future advancements that could improve the design of scenarios in epidemiological settings., Competing Interests: Declaration of Competing Interest MCR reports stock ownership in Becton Dickinson & Co., which manufactures medical equipment used in COVID-19 testing, vaccination, and treatment. JL has served as an expert witness on cases where the likely length of the pandemic was of issue. There are no other competing interests to declare., (Published by Elsevier B.V.)

Scenario-based modeling frameworks have been widely used to support policy-making at state and federal levels in the United States during the COVID-19 response. While custom-built models can be used to support one-off studies, sustained updates to projections under changing pandemic conditions requires a robust, integrated, and adaptive framework. In this paper, we describe one such framework, UVA-adaptive, that was built to support the CDC-aligned Scenario Modeling Hub (SMH) across multiple rounds, as well as weekly/biweekly projections to Virginia Department of Health (VDH) and US Department of Defense during the COVID-19 response. Building upon an existing metapopulation framework, PatchSim, UVA-adaptive uses a calibration mechanism relying on adjustable effective transmissibility as a basis for scenario definition while also incorporating real-time datasets on case incidence, seroprevalence, variant characteristics, and vaccine uptake. Through the pandemic, our framework evolved by incorporating available data sources and was extended to capture complexities of multiple strains and heterogeneous immunity of the population. Here we present the version of the model that was used for the recent projections for SMH and VDH, describe the calibration and projection framework, and demonstrate that the calibrated transmissibility correlates with the evolution of the pathogen as well as associated societal dynamics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: APP report grants from Metabiota Inc outside the submitted work. J.S. and Columbia University declare partial ownership of SK Analytics. No other authors have competing interests to declare., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Disease surveillance systems provide early warnings of disease outbreaks before they become public health emergencies. However, pandemics containment would be challenging due to the complex immunity landscape created by multiple variants. Genomic surveillance is critical for detecting novel variants with diverse characteristics and importation/emergence times. Yet, a systematic study incorporating genomic monitoring, situation assessment, and intervention strategies is lacking in the literature. We formulate an integrated computational modeling framework to study a realistic course of action based on sequencing, analysis, and response. We study the effects of the second variant's importation time, its infectiousness advantage and, its cross-infection on the novel variant's detection time, and the resulting intervention scenarios to contain epidemics driven by two-variants dynamics. Our results illustrate the limitation in the intervention's effectiveness due to the variants' competing dynamics and provide the following insights: i) There is a set of importation times that yields the worst detection time for the second variant, which depends on the first variant's basic reproductive number; ii) When the second variant is imported relatively early with respect to the first variant, the cross-infection level does not impact the detection time of the second variant. We found that depending on the target metric, the best outcomes are attained under different interventions' regimes. Our results emphasize the importance of sustained enforcement of Non-Pharmaceutical Interventions on preventing epidemic resurgence due to importation/emergence of novel variants. We also discuss how our methods can be used to study when a novel variant emerges within a population., Competing Interests: Competing interests statement:The authors declare no competing interest.

Competing Interests: The authors declare no conflicts of interest.

To demonstrate viral proteins/inflammatory cytokines in a patient with unilateral keratouveitis. Retrospective case report. A 70-year-old Asian-Indian male presented with acute onset of blurring of vision in the left eye (OS) of 2 days duration. He had was coronavirus disease 2019 (COVID-19)-positive 3 months earlier. He had undergone cataract surgery/retinal laser photocoagulation in both the eyes. The corrected distance visual acuity (CDVA) (Snellen) in the right eye (RE) (OD) and left eye (LE) (OS) was 20/20 and 20/80, respectively. OS showed decreased corneal sensation, Descemet's folds, mild stromal edema, and fine and pigmented keratic precipitates with anterior chamber 1+ flare and 1+ cells. Fundus evaluation showed scattered laser marks in the OD and temporal sectoral laser marks in OS. He was diagnosed with viral keratouveitis in OS. Tear samples were collected on Schirmer's strips and tear wash for mass spectrometry and cytokines, which had 368 and 451 viral proteins in the RE and LE, respectively, using nano liquid chromatography-mass spectrometry, which were more than controls. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and varicella zoster virus proteins were detected. Cytokine analysis using flow cytometer analysis showed higher inflammation in OS as compared to OD. The patient was treated with oral acyclovir and topical steroids and resulted in resolution of his keratouveitis. SARS-CoV-2 proteins were present in the tear sample 3 months after COVID-19. The presence of viral proteins does not indicate causality., Competing Interests: None

Characteristics and course of known seasonal diseases of pre-coronavirus disease (COVID-19) pandemic era may or may not change during the pandemic. Labelling COVID-19 as a novel etiology for those seasonal diseases or considering it as coinfection is debatable. Appropriate investigations are required to rule out previously known etiologies before correlating it with COVID-19. Epidemic retinitis (ER) or post fever retinitis is one such entity with seasonal variation. Multiple seropositivity for various organisms has been reported for ER during pre-pandemic era. This may significantly increase during the pandemic as the possibility of coinfection with COVID-19 is high. In the absence of gold-standard tests to exclude previously reported causes of ER, one should not undermine the possible coinfection before considering ER as post-COVID-19 syndrome. A study of incidence and pattern of seasonal variation of ER before and during the pandemic is needed before presumptively associating it with COVID-19.

Introduction: Coronavirus disease (COVID-19) vaccines have been reported to have ocular side effects including scleritis and episcleritis., Purpose: To report scleritis and episcleritis within a month following administration of COVID-19 vaccine., Methods: Retrospective case series., Results: 15 eyes of 12 consecutive patients with scleritis and episcleritis from March 2021 to September 2021 were included. The mean time of onset of symptoms in patients with scleritis was 15.7 days (range, 4-30) and for episcleritis it was 13.2 days (range 2-30). Patients received COVISHIELD™ (10 patients) and COVAXIN™ (2 patients). Five patients had denovo inflammation and seven had recurrent inflammation. Episcleritis patients were treated with topical steroids and systemic COX2 inhibitors while patients with scleritis were treated with topical steroids/oral steroids/antiviral medications depending on the aetiology., Conclusion: Scleritis and episcleritis following COVID-19 vaccination are milder and do not require intensive immunosuppression except in rare cases.

Purpose: To study the impact of the novel coronavirus disease-2019 (COVID-19) pandemic on incidence, seasonal variation, clinical presentation, and disease outcome of epidemic retinitis (ER) and to compare clinical outcomes with positive and negative COVID-19 serology., Methods: This is a retrospective, observational study conducted at a tertiary eye care hospital from August 2020 to June 2022. A graph of ER cases against the month of presentation was compared with the graph of the COVID-19 pandemic in the same region. Cases presented before COVID-19 vaccination, with positive COVID-19 serology (Group 1) were compared with cases with negative serology (Group 2)., Results: One hundred and thirty-two cases of ER were seen. The least number of cases were seen during and immediately after the peak of the pandemic (May 2021-August 2021). COVID-19 serology was positive in 13 (22 eyes)/60 (21.6%) unvaccinated cases. Along with COVID-19, positive serology for other ER etiologies was seen in 5/13 cases (38.4%). All patients received oral doxycycline with/without steroids. Groups 1 and 2 included 22 and 21 eyes of 13 cases each. Macular edema resolved in 43.6 and 32 days in groups 1 and 2, respectively. Retinitis resolved at 1 month in both groups. Corrected distant visual acuity was 20/50 and 20/70 at the presentation, which improved to 20/20 and 20/25 in groups 1 and 2, respectively. Mean and median follow-up was 6 months and 4.5 months, respectively, in both groups. No complications or recurrences were seen., Conclusion: No significant impact of the COVID-19 pandemic on ER was observed., Competing Interests: None

Purpose: To study the clinical presentation and treatment outcome of epidemic retinitis (ER) during pregnancy., Methods: This is a retrospective, observational chart review of pregnant patients diagnosed with ER from January 2014 to February 2023. Demographic details, month of pregnancy at the onset of ocular symptoms, history of present illness, clinical manifestations, and treatment outcomes were studied., Results: In 9 years, ER was seen in 86 females, of whom 12 (13.9%) were pregnant. Twenty-one eyes of those 12 patients were studied. Most of the patients presented in the sixth month of pregnancy (range: 5-9 months, mean: 6.3 months). Physicians diagnosed viral exanthematous fever in six, typhoid in three, and suspected rickettsia in one patient. Medical termination of pregnancy (MTP) was performed in two patients before presentation. Weil-Felix test was positive in five, Brucella in one, WIDAL in three, and coronavirus disease 2019 (COVID-19) IgG and dengue IgG in one patient each. Oral antibiotics were given in five patients (two post-medical termination of pregnancy [MTP]) for the retinitis. All except four received oral steroids. Mean presenting corrected distant visual acuity (n = 21) was 20/125 (range: 20/20-20/20,000), which improved to (n = 18) 20/30 (range: 20/20-20/240). Macular edema (n = 11) resolved in 33.18 days (range: 20-50 days), and retinitis (n = 13) resolved in 58 days (range: 30-110 days). Ocular and systemic examination of newborn was possible in two and the babies were normal., Conclusion: ER is seen commonly at the beginning of the third trimester. Lack of antibiotics may delay the resolution of retinitis. Ocular health needs to be assessed in larger series to conclude absence of retinal involvement in newborns., Competing Interests: None

The distinct disease progression patterns of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) indicate diverse host immune responses. SARS-CoV-2 severely impairs type I interferon (IFN) cell signaling, resulting in uncontrolled late-phase lung damage in patients. For better pharmacological properties, cytokine modifications may sometimes result in a loss of biological activity against the virus. Here, we employed the genetic code expansion and engineered IFN-β, a phase II clinical cytokine with 3-amino tyrosine (IFN-β-A) that reactivates STAT2 expression in virus-infected human cells through JAK/STAT cell signaling without affecting signal activation and serum half-life. This study identified that genetically encoded IFN-β-A might stabilize the protein-receptor complex and trigger JAK-STAT cell signaling, which is a promising modality for controlling SARS-CoV-2 infection., (© 2023 Wiley Periodicals LLC.)

Area deprivation index (ADI) is associated with the risk of severe COVID-19 in adults. However, this association has not been established in children. Information on ADI, demographics, clinical features, disease severity, and outcomes was analyzed for 3434 children with COVID-19. A multivariate logistic regression revealed that non-Hispanic Asians, extremes of weight, and higher ADI were associated with severe disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) may impair immune modulating host microRNAs, causing severe disease. Our objectives were to determine the salivary miRNA profile in children with SARS-CoV-2 infection at presentation and compare the expression in those with and without severe outcomes. Children <18 years with SARS-CoV-2 infection evaluated at two hospitals between March 2021 and February 2022 were prospectively enrolled. Severe outcomes included respiratory failure, shock or death. Saliva microRNAs were quantified with RNA sequencing. Data on 197 infected children (severe = 45) were analyzed. Of the known human miRNAs, 1606 (60%) were measured and compared across saliva samples. There were 43 miRNAs with ≥2-fold difference between severe and non-severe cases (adjusted p -value < 0.05). The majority (31/43) were downregulated in severe cases. The largest between-group differences involved miR-4495, miR-296-5p, miR-548ao-3p and miR-1273c. These microRNAs displayed enrichment for 32 gene ontology pathways including viral processing and transforming growth factor beta and Fc-gamma receptor signaling. In conclusion, salivary miRNA levels are perturbed in children with severe COVID-19, with the majority of miRNAs being down regulated. Further studies are required to validate and determine the utility of salivary miRNAs as biomarkers of severe COVID-19.

A 36-year-old Asian Indian male presented with redness and pain in his right eye of 1 week duration. He was diagnosed to have right acute anterior uveitis and had a history of being admitted at a local hospital for dengue hepatitis a month earlier. He had been on adalimumab 40 mg three weekly once and oral methotrexate 20 mg/week for human leucocyte antigen (HLA) B27 spondyloarthropathy and recurrent anterior uveitis. Our patient had re-activation of his anterior chamber inflammation on three distinct occasions: first, 3 weeks following recovery from coronavirus disease 2019 (COVID-19), the second after the second dose of COVID-19 vaccination, and the third after recovery from dengue fever-associated hepatitis. We propose molecular mimicry and bystander activation as the postulated mechanisms for the re-activation of his anterior uveitis. In conclusion, patients with auto-immune diseases can have recurrent ocular inflammation following COVID-19 or its vaccination or dengue fever as seen in our patient. The anterior uveitis is usually mild and responds to topical steroids. Additional immuno-suppression may not be needed. Mild ocular inflammation following vaccination should not deter individuals from getting COVID-19 vaccination., Competing Interests: None

The aim of this study is to report the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management outcomes in a series of three cases of varicella zoster virus (VZV) reactivation following one dose of coronavirus disease 2019 (COVID-19) vaccination. This was a retrospective and observational study. All the patients who developed uveitis post-vaccination were pooled together. Patients who had VZV reactivation were included. Two cases had polymerase chain reaction positive for VZV from aqueous humor. At the time of presentation, IgG and IgM spike protein antibodies for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were tested. Out of this pool, three patients with classical features to describe pole-to-pole manifestations were chosen. A 36-year-old lady with post-vaccination sclerokeratouveitis associated with reactivation of herpes zoster ophthalmicus, a 56-year-old lady with post-vaccination acute anterior uveitis associated with herpes zoster ophthalmicus, and a 43-year-old gentleman with post-vaccination acute retinal necrosis were included. We present a possible link between anti-SARS-CoV-2 virus vaccination and varicella zoster reactivation in these patients and also describe the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management with detailed discussion., Competing Interests: None

Being highly transmissible, severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected millions of people causing devastating global impact and has also not slowed down even after vaccination. The emerges of new strains has made more concerns than the original one. We need a new therapeutic approach against the disease. Our comprehensive in silico study investigates dual herbal combinatorial methanolic extracts of W. somnifera (W) alone and with P. emblica (P) (W:P/1:4) , T. sinensis (T) (W:T/1:4), B. monnieri (B) (W:B/1:1), O. basilicum (O) (W:O/1:4), A. racemosus (A) (W:A/4:1) for potential four phytochemicals as ligands docked with eight COVID-19 Nonstructural proteins (nsp)-main protease (PDB ID:6LU7), papain-like protease (6WUU), helicase ADP (2XZL), N7-methyltransferase (5C8S), endoribonuclease (6WLC), 2'O-methyltransferase (6WVN), RNA dependent RNA polymerase (6M71), and 3Cprotease (6YNQ) along with Remdesivir and Hydroxychloroquine. Ligands from W:P/1:4 showed remarkable docking score (-9.01 kcal/mol) 6M71-(8E,11E,14E)-eicosa-8,11,14-trienoicacidmethylester (EIS) and (-9.99 kcal/mol) 6YNQ-N-[(E)-[4-[(2-methoxydibenzofuran-3-yl)amino]-4-oxobutan-2-ylidene]amino] 4nitrobenzamide (MET). Further, MD simulations were studied for 100 ns and showed the complexes were flexible, stable in the binding pockets of the receptors, and MM-PBSA analysis determined high binding energy of -129.673 ± 15.284 and -134.594 ± 7.085 for 6M71-EIS (Asn 496 , Lys 577 , Arg 569 ) and 6YNQ-MET (Cys 145 , His 41 ). Finally, in vitro JURKAT E6.1 cell lines treated with W:P/1:4 and W:O/1:4 methanolic extracts yielded 44.06 and 31.53 ng/mL levels for interferon alpha to counteract an external stimulus by establishing an antiviral state. Thus, nsp is targeted to design effective antiviral drugs for developing an effective therapeutic approach to combat viral RNA synthesis, processing, and suppression of host immunity.Communicated by Ramaswamy H. Sarma.

Background: Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022., Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1-4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models' predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models' forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models' past predictive performance., Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models' forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models' forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models' forecasts of deaths (N=763 predictions from 20 models). Across a 1-4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models., Conclusions: Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks., Funding: AA, BH, BL, LWa, MMa, PP, SV funded by National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and respectively Virginia Dept of Health Grant VDH-21-501-0141, VDH-21-501-0143, VDH-21-501-0147, VDH-21-501-0145, VDH-21-501-0146, VDH-21-501-0142, VDH-21-501-0148. AF, AMa, GL funded by SMIGE - Modelli statistici inferenziali per governare l'epidemia, FISR 2020-Covid-19 I Fase, FISR2020IP-00156, Codice Progetto: PRJ-0695. AM, BK, FD, FR, JK, JN, JZ, KN, MG, MR, MS, RB funded by Ministry of Science and Higher Education of Poland with grant 28/WFSN/2021 to the University of Warsaw. BRe, CPe, JLAz funded by Ministerio de Sanidad/ISCIII. BT, PG funded by PERISCOPE European H2020 project, contract number 101016233. CP, DL, EA, MC, SA funded by European Commission - Directorate-General for Communications Networks, Content and Technology through the contract LC-01485746, and Ministerio de Ciencia, Innovacion y Universidades and FEDER, with the project PGC2018-095456-B-I00. DE., MGu funded by Spanish Ministry of Health / REACT-UE (FEDER). DO, GF, IMi, LC funded by Laboratory Directed Research and Development program of Los Alamos National Laboratory (LANL) under project number 20200700ER. DS, ELR, GG, NGR, NW, YW funded by National Institutes of General Medical Sciences (R35GM119582; the content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the National Institutes of Health). FB, FP funded by InPresa, Lombardy Region, Italy. HG, KS funded by European Centre for Disease Prevention and Control. IV funded by Agencia de Qualitat i Avaluacio Sanitaries de Catalunya (AQuAS) through contract 2021-021OE. JDe, SMo, VP funded by Netzwerk Universitatsmedizin (NUM) project egePan (01KX2021). JPB, SH, TH funded by Federal Ministry of Education and Research (BMBF; grant 05M18SIA). KH, MSc, YKh funded by Project SaxoCOV, funded by the German Free State of Saxony. Presentation of data, model results and simulations also funded by the NFDI4Health Task Force COVID-19 (https://www.nfdi4health.de/task-force-covid-19-2) within the framework of a DFG-project (LO-342/17-1). LP, VE funded by Mathematical and Statistical modelling project (MUNI/A/1615/2020), Online platform for real-time monitoring, analysis and management of epidemic situations (MUNI/11/02202001/2020); VE also supported by RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), the CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17-043/0009632), RECETOX RI project (CZ.02.1.01/0.0/0.0/16-013/0001761). NIB funded by Health Protection Research Unit (grant code NIHR200908). SAb, SF funded by Wellcome Trust (210758/Z/18/Z)., Competing Interests: KS, HG, RG, HJ, RN, BP, FS, JD, DW, SA, AU, GG, ER, NR, DS, YW, NW, LW, JT, GO, TS, DT, LP, EK, JM, MB, NL, JM, JS, JW, JF, BL, IR, JB, RW, IV, VT, MS, MZ, CP, BR, NB, SM, LC, GF, IM, DO, PA, AM, VE, AK, DK, LP, BD, ML, SS, JD, SM, VP, GR, BB, GA, NP, GZ, WB, SH, TH, DS, MG, JA, DM, SA, EA, DL, CP, JB, AR, TZ, AK, JZ, FP, FD, MC, GL, PG, BT, FB, GJ, MM, AF, AS, PM, AA, BH, BL, MM, PP, SV, RB, FD, AG, KG, MG, BK, AM, KN, JN, MR, FR, MS, ES, JZ, JK, BP, KH, YK, MS, BP, MB, MF, RI, TK, TO, JB, SF No competing interests declared, PB, HG, SS, BS Affiliated with IEM, Inc. The author has no financial interests to declare

During the Coronavirus Disease 2019 (COVID-19) pandemic, we have witnessed increase in number of reports of a known uveitic entity being associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Causal relation is yet to be proven for many reports. Perhaps, occurrence of a previously known region-specific endemic disease or closely resembling manifestations of a known disease in a non-endemic region during the COVID-19 pandemic might suggest a causal relationship. Epidemic retinitis (ER) or post fever retinitis is such condition with geographic variation. Occurrence of ER or ER-like manifestations in a non-endemic country during the pandemic should instigate further studies to consider SARS-CoV-2 as a causative organism.

Purpose: To assess the differences in the pattern of presentation of glaucoma emergency conditions during the various phases of pandemic-related travel restrictions: first wave-related lockdown, unlock period, and the second wave-related lockdown., Methods: The number of new emergency glaucoma conditions, the various diagnoses, and the total number of all new glaucoma patients presenting to the glaucoma services at five tertiary eye care centers in south India from 24 th March 2020 to 30 th June 2021 were collected from the electronic medical records and were analyzed. The data were compared with the corresponding time period in the year 2019., Results: In total, 620 patients presented with an emergency glaucoma diagnosis during the first wave-related lockdown as against 1337 during the same period in 2019 (P < 0.0001). During the unlock period, 2659 such patients visited the hospital compared with 2122 in 2019 (P = 0.0145). During the second wave-related lockdown, there were 351 emergency patients compared with 526 patients in 2019 (P < 0.0001). Lens-induced glaucomas (50.4%) and neovascular glaucoma (20.6%) were the most common diagnoses during the first wave-related lockdown. During the unlock period, there was a greater proportion of neovascular glaucoma (P = 0.0123). The second wave-related lockdown had a greater proportion of phacolytic glaucomas (P = 0.005) and acute primary angle closure (P = 0.0397) patients., Conclusion: The study demonstrates that emergency glaucoma care was grossly underutilized by the people during the lockdowns. Trivial conditions like cataracts or retinal vascular diseases if not treated appropriately may progress to become emergencies in the future., Competing Interests: None

Background: Prolonged use of N95 masks by healthcare workers might affect physical health due to mask-related hypoxia in addition to the psychological effects of N95 masks. We tried to explore the association of N95 mask-related hypoxia and headache with stress, quality of sleep, and anxiety in the current study., Materials and Methods: The sample (N = 78) consisted of 41 doctors and 37 nurses involved in COVID-19 patient care and using N95 masks with or without PPE for at least 4 hours. Perceived stress scale (PSS), Coronavirus anxiety scale (CAS), and Pittsburgh sleep quality index (PSQI) were administered, and physical parameters like heart rate and oxygen saturation (SpO2) were measured., Results: Around 42% of the study participants experienced headaches after wearing an N95 mask and had a higher increase in heart rate (mean percent:10.5% vs 6.3%) and decline in SpO2 (mean percent: 2.6% vs 1.5%) compared to those who didn't develop a headache after N95 mask use. Independent samples t-test showed a mean difference for PSS and CAS between those who experienced headaches and those who didn't. The mean PSQI scores among the study participants were 8.91 ± 5.78; the score among those participants with and without headache was 10.57 ± 3.11 and 7.68 ± 2.53, respectively., Conclusion: Perceived corona anxiety, poor sleep quality, and corona anxiety are associated with N95-related headaches and SpO2 drop among health professionals who wear N95 masks for at least 4 hours., (© Journal of the Association of Physicians of India 2011.)

Background: Near-peer medical education serves as an important method of delivering education to junior students by senior students. Due to the reduced clinical exposure because of the COVID-19 pandemic, we developed a mentorship scheme to help medical students with their Integrated Structured Clinical Examinations (ISCEs) by providing a combination of near-peer mentorship together with lecture-based teaching on a weekly basis for a 12-week period. Students attended a specialty-focused lecture every Tuesday followed by a small group teaching session organised by their tutor., Methods: A longitudinal evaluative interventional study was undertaken by the international student led medical education organisation, OSCEazy. The teaching programme was organised and conducted by third year medical students to a recruited cohort of second year medical students. Students' perceptions of ISCEs (confidence, anxiety, and overall performance) were evaluated using 5-point Likert scales while their knowledge of the specialty was assessed using 10 single best answer questions which were distributed via Google® forms at the start and end of each week. In addition, we assessed tutor perceptions of their teaching and learning experience., Results: Seventy-two tutees were enrolled in the programme (mean age: 24.4, female: 77.8%). 88.9% of the participants had not attended any online ISCE teaching prior to this. They preferred in-person ISCE teaching as compared to virtual sessions [median 4.5 (IQR 4-5) vs 3 (IQR 3-4), p <  0.0001), respectively]. There was a significant overall increase in knowledge when comparing pre-session and post-session performance [mean 53.7% vs 70.7%, p <  0.0001)]. There was a significant increase in student confidence [Confidence: median 3 (IQR:3-4) vs 4 (IQR 3-4), p <  0.0001] while no change was seen in the anxiety and perception of their overall performance in an ISCE. [Anxiety: median 3 (IQR 2-4) vs 3 (IQR 3-4), p = 0.37, Performance: median 3 (IQR 3-4) vs median 3 (IQR 3-4), p <  0.0001]. The tutors reported an increase in their confidence in teaching ISCEs online [median 3 (IQR 2-3.25) vs median 4 (IQR 4-5), p <  0.0001)]., Conclusion: Online near-peer teaching increases the confidence of both tutees and tutors involved while enhancing the tutees' knowledge of the specialty. Thus, medical schools should incorporate near-peer teaching in their curriculum to enhance the student learning experience., (© 2023. The Author(s).)

Background: Perfluoroalkylated substances (PFAS) are man-made, persistent organic compounds with immune-modulating potentials. Given that pregnancy itself represents an altered state of immunity, PFAS exposure-related immunotoxicity is an important environmental factor to consider in SARS-CoV-2 infection during pregnancy as it may further affect humoral immune responses., Aim: To investigate the relationship between maternal plasma PFAS concentrations and SARS-CoV-2 antibody levels in a NYC-based pregnancy cohort., Methods: Maternal plasma was collected from 72 SARS-CoV-2 IgG + participants of the Generation C Study, a birth cohort established at the beginning of the COVID-19 pandemic in New York City. Maternal SARS-CoV-2 anti-spike IgG antibody levels were measured using ELISA. A panel of 16 PFAS congeners were measured in maternal plasma using a targeted UHPLC-MS/MS-based assay. Spearman correlations and linear regressions were employed to explore associations between maternal IgG antibody levels and plasma PFAS concentrations. Weighted quantile sum (WQS) regression was also used to evaluate mixture effects of PFAS. Models were adjusted for maternal age, gestational age at which SARS-CoV-2 IgG titer was measured, COVID-19 vaccination status prior to IgG titer measurement, maternal race/ethnicity, parity, type of insurance and pre-pregnancy BMI., Results: Our study population is ethnically diverse with an average maternal age of 32 years. Of the 16 PFAS congeners measured, nine were detected in more than 60% samples. Importantly, all nine congeners were negatively correlated with SARS-CoV-2 anti-spike IgG antibody levels; n-PFOA and PFHxS, PFHpS, and PFHxA reached statistical significance (p < 0.05) in multivariable analyses. When we examined the mixture effects using WQS, a quartile increase in the PFAS mixture-index was significantly associated with lower maternal IgG antibody titers (beta [95% CI] = -0.35 [-0.52, -0.17]). PFHxA was the top contributor to the overall mixture effect., Conclusions: Our study results support the notion that PFAS, including short-chain emerging PFAS, act as immunosuppressants during pregnancy. Whether such compromised immune activity leads to downstream health effects, such as the severity of COVID-19 symptoms, adverse obstetric outcomes or neonatal immune responses remains to be investigated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data., (© 2023. The Author(s).)

Introduction: Corona virus disease (COVID-19) has been associated with ophthalmic manifestations which can occur during or following the infection., Purpose: To explore the systemic status in ophthalmic patients who had a recent history of COVID-19 or those with positive COVID-19 antibody status., Methods: Retrospective case series., Results: 30 patients with history of COVID-19 infection and positive COVID-19 antibodies were included in the study. The median age was 49 years (mean 48.7 ± 13.7 years), 20 were males (66.7%) and 10 (33.3%) were females. Patients with VA>/= 6/60 were included in group 1 and those with VA<6/60 were included in group 2. D-dimer/serum Ferritin levels were raised in group 2 compared to group 1with (p=0.013) / (p=0.018) respectively., Conclusion: Serum D-dimer and ferritin levels were statistically significant and were higher in patients with sight threatening ocular manifestations. ESR and CRP were raised even after recovery from COVID-19 although they were not statistically significant.

Objectives: To study the role of combined CTPA and indirect CT venogram to diagnose venous thromboembolism (VTE) in patients with COVID-19 pneumonia and to compare the clinical characteristics, laboratory parameters, CT findings and clinical outcomes between the VTE positive and negative groups., Methods: In this retrospective study, 131 patients with COVID-19 pneumonia who underwent CTPA and venogram between August 2020 and January 2021 were included. Relevant demographical, clinical and laboratory data and CT images were collected. Two thoracic radiologists independently reviewed the CTPA and venogram images., Results: VTE was identified in 29 patients (22% of the study population). CT venogram identified DVT in 9 patients. No statistical difference was observed between the two groups with respect to age, gender, BMI and presence of comorbidities. There was a significant difference in the hospital stay duration, which is increased in the VTE positive group. The number of patients who were dependent on oxygen and mortality were also high in the positive group. There was statistically significant difference in the mean D-dimer value and the mean Neutrophil/lymphocyte ratio, which were higher in the VTE positive group., Conclusion: Combined CTPA and venogram can be used as a one-stop investigation for diagnosing PE and DVT of lower limbs in patients with COVID-19 pneumonia. CTPA with venogram should be performed in patients with D-dimer value in the range of 1000 - 1200 μg/L and above to rule out VTE as the hospital stay duration and final outcomes vary between the positive and negative groups.

Background: Diarrhea is present in up to 30-50% of patients with COVID-19. The mechanism of SARS-CoV-2-induced diarrhea remains unclear. We hypothesized that enterocyte-enteric neuron interactions were important in SARS-CoV-2-induced diarrhea. SARS-CoV-2 induces endoplasmic reticulum (ER) stress in enterocytes causing the release of damage associated molecular patterns (DAMPs). The DAMPs then stimulate the release of enteric neurotransmitters that disrupt gut electrolyte homeostasis., Methods: Primary mouse enteric neurons (EN) were exposed to a conditioned medium from ACE2-expressing Caco-2 colonic epithelial cells infected with SARS-CoV-2 or treated with tunicamycin (ER stress inducer). Vasoactive intestinal peptides (VIP) expression and secretion by EN were assessed by RT-PCR and ELISA, respectively. Membrane expression of NHE3 was determined by surface biotinylation., Results: SARS-CoV-2 infection led to increased expression of BiP/GRP78, a marker and key regulator for ER stress in Caco-2 cells. Infected cells secreted the DAMP protein, heat shock protein 70 (HSP70), into the culture media, as revealed by proteomic and Western analyses. The expression of VIP mRNA in EN was up-regulated after treatment with a conditioned medium of SARS-CoV-2-infected Caco-2 cells. CD91, a receptor for HSP70, is abundantly expressed in the cultured mouse EN. Tunicamycin, an inducer of ER stress, also induced the release of HSP70 and Xbp1s, mimicking SARS-CoV-2 infection. Co-treatment of Caco-2 with tunicamycin (apical) and VIP (basolateral) induced a synergistic decrease in membrane expression of Na + /H + exchanger (NHE3), an important transporter that mediates intestinal Na + /fluid absorption., Conclusions: Our findings demonstrate that SARS-CoV-2 enterocyte infection leads to ER stress and the release of DAMPs that up-regulates the expression and release of VIP by EN. VIP in turn inhibits fluid absorption through the downregulation of brush-border membrane expression of NHE3 in enterocytes. These data highlight the role of epithelial-enteric neuronal crosstalk in COVID-19-related diarrhea.

SARS-CoV-2 has mutated many times among different populations. We analyzed wild-type spike protein and 18 different variants of SARS-CoV-2 spike protein known until the beginning of 2022 (alpha, beta, B.1.429, B.1.616, B.1.620, B.1.617.3, C.1.2, delta, epsilon, eta, gamma, iota, kappa, lambda, mu, omicron, theta, and zeta) for their interaction with 16 phytocompounds and remdesivir, resulting into 425 combinations. The largest number of mutations has been reported in the omicron followed by delta variant. However, the virulence of the delta variant has been reported higher as compared to omicron. Mutations at a few locations (D215G, K417N, E484K, N501Y, D614G, and P681H) were common in most of the variants. 3 D structures of all the 18 spike proteins were created using SWISS-MODEL to test the binding affinities with caffeine theophylline, emodin, vitexin, berberine, curcumin, piperine, quercetin, artemisinin, carvacrol, capsaicin, tetrahydrocannabinol, cannabidiol, α- pinene, β- pinene and gingerol. Phytocompounds and mutant variants were prepared using AutoDock 4.2.6 software. Binding affinities of the selected phytocompounds with the different mutant spike proteins were achieved using AutoDock Vina. Out of all combinations investigated, the best binding affinities were observed with 3 variants of SAR-CoV-2 with 5 phytocompounds along with remdesivir. The range of best binding energies varied from -9.1 to -8.0 kcal/mol. Further, MD simulation was done for selected 9 phytocompound-spike mutant complexes for analyzing the stability of interactions for 100 ns. ADMET studies via ProTox-II and SwissADME displayed that phytocompounds are safe and less toxic in comparison to remdesivir.Communicated by Ramaswamy H. Sarma.

Purpose: To present the clinical features of a rare case of varicella zoster infection following one dose of Coronavirus Disease 2019 (COVID-19) vaccination in an elderly Asian Indian male., Methods: Retrospective observational case report., Results: A 71-year-old gentleman presented to us with complaints of reduced vision associated with redness and pain in his right eye for 1 week. On examination he revealed a right eye pan uveitis picture with circumcorneal congestion, multiple fine keratic precipitates, anterior chamber cells and flare, vitritis and widespread areas of acute retinal necrosis. His left eye was within normal limits. Ten days prior to the presentation he had received the first dose of COVID-19 vaccine following which he had developed fever for 2 days that preceded the red eye. The patient's aqueous sample tested positive for varicella zoster virus (VZV) by nested polymerase chain reaction (PCR) method. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in reverse transcriptase polymerase chain reaction (RT-PCR) assay from the aqueous and also from the nasopharyngeal swab was negative., Conclusion and Significance: To the best of our knowledge this is the earliest description of a case that has a viral reactivation following COVID-19 vaccination. Elderly people with pre-existing comorbidities, may be at a risk of both primary coronavirus infection and unconceivable risk of aberrant immune reactions leading to a different virus infection or reactivation need to be kept in mind. We present a possible link between SARS-CoV-2 virus vaccination and varicella zoster reactivation in this patient.

Background: Corneal melt with iris prolapse is a rare complication of autoimmune diseases, especially rheumatoid arthritis., Purpose: To highlight a challenging case of a peripheral ulcerative keratitis (PUK) with corneal melt and iris prolapse in a patient's only eye., Synopsis: A 56-year-old Asian Indian male presented with blurring of vision in the right eye and was diagnosed with cataract. He was a known type 2 diabetes mellitus and a rheumatoid arthritis patient and was not on treatment. He had been previously diagnosed with PUK in the left eye and was lost to follow-up due to coronavirus disease 2019 (COVID-19) after therapeutic penetrating keratoplasty and lost his vision in that eye. Cataract surgery in the right eye was done under cover of immunosuppression. Subsequently, he developed PUK and was treated with a glue and bandage contact lens. Again, he was lost to follow-up and then presented a few months later with corneal melt with iris prolapse in the right eye. We describe in the video the surgical and medical challenges and successful salvage of both the eyeball and the vision., Highlights: Highlights include the following: 1. A rare case of corneal melt with iris prolapse. 2. Demonstration of surgical technique of patch graft. 3. Anterior segment optical coherence tomography before and after the procedure., Video Link: https://youtu.be/HbgixlEAYKU.

Objectives: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years., Study Design: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups., Results: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic., Conclusions: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Treating chronic macular edema (CME) post endophthalmitis is a challenge. Use of steroids may reactivate the infection and repeated intravitreal therapy with anti-vascular growth factor inhibitors (Anti-VEGF) puts the patient again at the risk of exacerbation of inflammation or endophthalmitis. We describe a case of CME post traumatic endophthalmitis successfully treated with topical interferon therapy., Case Description: A 34-year-old Asian Indian lady with a history of cat bite to her right eye and treated elsewhere as traumatic endophthalmitis with recurrent macular edema, presented to us 1 year after the injury. She had received anti-VEGF injection for same. Her medical history was non-contributory except for close contact with her cat. Therapeutic trials with oral doxycycline followed by oral albendazole with steroids, as well as repeated anti-VEGF therapy failed to prevent recurrence of CME. Patient's steroid responsiveness and reluctance for injections, made us to opt for a novel topical Interferon therapy. Macular edema resolved in 2 months. Interruption of interferon therapy due to COVID-lock down resulted in recurrence of the CME, which again responded well to interferon monotherapy., Conclusion: Topical interferon may have a role in the treatment of inflammatory macular edema and can serve as a, safer, economical and non-invasive treatment option compared to intravitreal steroids and anti-VEGFs.

The rural communities of the sub-Sahara regions in Africa are rich in diverse indigenous culinary knowledge and foods, food crops, and condiments such as roots/tubers, cereal, legumes/pulses, locust beans, and green leafy vegetables. These food crops are rich in micronutrients and phytochemicals, which have the potentials to address hidden hunger as well as promote health when consumed. Some examples of these are fermented foods such as ogi and plants such as Vernonia amygdalina (bitter leaf), Zingiber officinales (garlic), Hibiscus sabdariffa (Roselle), and condiments. Food crops from West Africa contain numerous bioactive substances such as saponins, alkaloids, tannins, phenolics, flavonoids, and monoterpenoid chemicals among others. These bioresources have proven biological and pharmacological activities due to diverse mechanisms of action such as immunomodulatory, anti-inflammatory, antipyretic, and antioxidant activities which made them suitable as candidates for nutraceuticals and pharma foods. This review seeks to explore the different processes such as fermentation applied during food preparation and food crops of West-African origin with health-promoting benefits. The different bioactive compounds present in such food or food crops are discussed extensively as well as the diverse application, especially regarding respiratory diseases. PRACTICAL APPLICATIONS: The plants and herbs summarized here are more easily accessible and affordable by therapists and others having a passion for promising medicinal properties of African-origin plants.The mechanisms and unique metabolic potentials of African food crops discussed in this article will promote their applicability as a template molecule for novel drug discoveries in treatment strategies for emerging diseases. This compilation of antiviral plants will help clinicians and researchers bring new preventive strategies in combating COVID-19 like viral diseases, ultimately saving millions of affected people., (© 2022 Wiley Periodicals LLC.)

College students experienced increased stress and anxiety during the COVID-19 pandemic. This study evaluated the effect of brief online Isha Upa Yoga modules on undergraduates' mental health and well-being. Randomized control trial (RCT) with waitlist control crossover (N = 679). The intervention group was instructed to learn and practice the modules daily for 12 weeks. At the end of the 4-week RCT, the control group was instructed to learn and practice the modules for the remaining 8 weeks. Primary outcomes included stress and well-being. Secondary outcomes included anxiety, depression, resilience, positive affect and negative affect. Linear mixed-effects models were used for analyses. Isha Upa Yoga significantly reduced stress (Group [intervention, control] × Time [baseline, Week 4] interaction, p = .009, d = .27) and increased well-being (Group × Time interaction p = .002, d = .32). By the study's end, the intervention and control groups experienced significant improvements in well-being (p < .001, p < .001), stress (p < .001, p < .001), anxiety (p < .001, p < .001), depression (p < .001, p = .004), positive affect (p = .04, p < .001), and negative affect (p < .001, p < .001). Online Isha Upa Yoga shows promise for mitigating the pandemic's negative impact on undergraduates' mental health and improving their well-being., (© 2022 The International Association of Applied Psychology.)

Background: This study documents the experience of an academic medical center implementing SARS-CoV2 screening of asymptomatic research personnel to support the "return-to-work" initiative and donor cadavers to support in-person student education., Methods: Testing was performed on samples received June 1, 2020 (for the cadaver program) and July 20, 2020 (for the personnel screening program) through September 30, 2021. Data were evaluated to document the number of cases and the positivity rate., Results: Approximately 3000 specimens were tested across both programs, with an overall positivity rate of 2.5% and 3.6% in the personnel and cadaver screening programs, respectively., Discussion: This screening program serves as an example of institutional investment in the safety of its faculty, staff, and students alike to address specific needs of a global pandemic., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Increasing fungal infections in immunocompromised hosts are a growing concern for global public health. Along with treatments, preventive measures are required. The emergence of reverse vaccinology has opened avenues for using genomic and proteomic data from pathogens in the design of vaccines. In this work, we present a comprehensive collection of various computational tools and databases with potential to aid in vaccine development. The ongoing pandemic has directed attention toward the increasing number of mucormycosis infections in COVID-19 patients. As a case study, we developed a computational pipeline for assisting vaccine development for mucormycosis. We obtained 6 proteins from 29,447 sequences from UniProtKB as potential vaccine candidates against mucormycosis, fulfilling multiple criteria. These criteria included potential characteristics, namely adhesin properties, surface or extracellular localization, antigenicity, no similarity to any human proteins, nonallergenicity, stability in vitro , and expression in fungal cells. These six proteins were predicted to have B cell and T cell epitopes, proinflammatory inducing peptides, and orthologs in several mucormycosis-causing species. These data could aid in vaccine development against mucormycosis for at-risk individuals.

Background: Chronic disease causes skeletal muscle loss that contributes to morbidity and mortality. There are limited data on the impact of dynamic muscle loss on clinical outcomes in COVID-19. We hypothesized that acute COVID-19-related muscle loss (acute sarcopenia) is associated with adverse outcomes., Methods: A retrospective analysis of a prospective clinical registry of COVID-19 patients was performed in consecutive hospitalized patients with acute COVID-19 (n = 95) and compared with non-COVID-19 controls (n = 19) with two temporally unique CT scans. Pectoralis muscle (PM), erector spinae muscle (ESM) and 30 day standardized per cent change in cross sectional muscle area were quantified. Primary outcomes included mortality and need for intensive care unit (ICU) admission. Multivariate linear and logistic regression were performed. Cox proportional hazard ratios were generated for ICU admission or mortality for the per cent muscle loss standardized to 30 days., Results: The COVID-19 CT scan cohort (n = 95) had an average age of 63.3 ± 14.3 years, comorbidities including COPD (28.4%) and diabetes mellitus (42.1%), and was predominantly Caucasian (64.9%). The proportion of those admitted to the ICU was 54.7%, with 10.5% requiring tracheostomy and overall mortality 16.8%. Median duration between CT scans was 32 days (IQR: 16-63 days). Significant reductions in median per cent loss was noted for PM (-2.64% loss [IQR: -0.28, -5.47] in COVID-19 vs. -0.06 loss [IQR: -0.01, -0.28] in non-COVID-19 CT controls, P < 0.001) and ESM (-1.86% loss [IQR: -0.28, -5.47] in COVID-19 vs. -0.06 loss [IQR: -0.02, -0.11]) in non-COVID-19 CT controls, P < 0.001). Multivariate linear regression analysis of per cent loss in PM was significantly associated with mortality (-10.8% loss [95% CI: -21.5 to -0.19]) and ICU admission (-11.1% loss [95% CI: -19.4 to -2.67]), and not significant for ESM. Cox proportional hazard ratios demonstrated greater association with ICU admission (adj HR 2.01 [95% CI: 1.14-3.55]) and mortality (adj HR 5.30 [95% CI: 1.19-23.6]) for those with significant per cent loss in PM, and greater association with ICU admission (adj HR 8.22 [95% CI: 1.11-61.04]) but not mortality (adj HR 2.20 [95% CI: 0.70-6.97]) for those with significant per cent loss in ESM., Conclusions: In a well-characterized cohort of 95 hospitalized patients with acute COVID-19 and two temporally distinct CT scans, acute sarcopenia, determined by standardized reductions in PM and ESM, was associated with worse clinical outcomes. These data lay the foundation for evaluating dynamic muscle loss as a predictor of clinical outcomes and targeting acute sarcopenia to improve clinical outcomes for COVID-19., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction: As the world fights the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several reports of retinal manifestations of the disease are emerging. Post fever retinitis is a well reported ocular inflammatory reaction to multiple invasive agents, be it virus, bacteria or other microbial agent., Purpose: We report an interesting case of bilateral multifocal retinitis with multiple vascular occlusions in a patient, three weeks after a febrile illness., Results: Investigations to ascertain the cause of fever resulted in identifying ephemeral seropositivity for several different Ribonucleic acid (RNA) viruses. The retinitis was managed with systemic steroids, doxycycline and anticoagulants with improvement in vision., Conclusion: High and persistent seropositive response against (SARS-CoV-2) helped us to narrow it as the causative agent but the cross reactivity of SARS-CoV-2 with other viruses can be misleading and needs careful interpretation.

Purpose: Worldwide, radiologists are experiencing increasing clinical workloads with associated increased burnout. This paper will review burnout definitions, prevalence, and causes. We will also share data from a survey of US neuroradiologists as an example of the impact of work-work imbalances from clinical overload. This article examines the impact on several key job indicators and upon the quality of the neuroradiology work environment in one nation. Finally, we will review proposals for ameliorating and preventing radiologist burnout., Method: A survey was sent to members of the American Society of Neuroradiology (ASNR) practicing in the US. Selected measures included workhours and volume, burnout symptoms, subjectively reported errors, participation in non-clinical activities, perceived interpretation quality, results communication, and consideration of early retirement., Results: Survey respondents (n = 412) included 57.5% with teaching responsibilities. Cutbacks in teaching, mentoring, research and/or practice building were reported by 86.2% of respondents. Subjective errors were reported as occurring sometimes or more frequently in the majority of respondents (56.9%) and were increased with faster than optimal speeds of interpretation (P < 0.001) and signing (P < 0.001). At least one burnout measure was reported by 85.2% of respondents., Conclusions: Increasing clinical demands in conjunction with a more challenging work environment impacts the ability of radiologists to perform core non-interpretive duties that are critical for success in both private and academic practice and is associated with burnout symptoms and adverse effects on quality. While this survey does not prove causation, the trends and findings are concerning and warrant both close monitoring and appropriate intervention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic has affected all people across the globe. Regional and community differences in timing and severity of surges throughout the pandemic can provide insight into risk factors for worse outcomes in those hospitalized with COVID-19., Methods: The study cohort was derived from the Cerner Real World Data (CRWD) COVID-19 Database made up of hospitalized patients with proven infection from December 1, 2019 through November 30, 2020. Baseline demographic information, comorbidities, and hospital characteristics were obtained. We performed multivariate analysis to determine if age, race, comorbidity and regionality were predictors for mortality, ARDS, mechanical ventilation or sepsis hospitalized patients with COVID-19., Results: Of 100,902 hospitalized COVID-19 patients included in the analysis (median age 52 years, IQR 36-67; 50.7% female), COVID-19 case fatality rate was 8.5% with majority of deaths in those ≥ 65 years (70.8%). In multivariate analysis, age ≥ 65 years, male gender and higher Charlson Comorbidity Index (CCI) were independent risk factors for mortality and ARDS. Those identifying as non-Black or non-White race have a marginally higher risk for mortality (OR 1.101, CI 1.032-1.174) and greater risk of ARDS (OR 1.44, CI 1.334-1.554) when compared to those who identify as White. The risk of mortality or ARDS was similar for Blacks as Whites. Multivariate analysis found higher mortality risk in the Northeast (OR 1.299, CI 1.22-1.29) and West (OR 1.26, CI 1.18-1.34). Larger hospitals also had an increased risk of mortality, greatest in hospitals with 500-999 beds (OR 1.67, CI 1.43-1.95)., Conclusion: Advanced age, male sex and a higher CCI predicted worse outcomes in hospitalized COVID-19 patients. In multivariate analysis, worse outcomes were identified in small minority populations, however there was no difference in study outcomes between those who identify as Black or White., (© 2022. The Author(s).)

Introduction: Corona virus disease (COVID-19) has been associated with a variety of ophthalmic manifestations including acute macular neuroretinopathy and paracentral middle maculopathy. Posterior segment manifestations after post COVID-19 vaccinations have been reported., Case Report: A 25- year-old Asian Indian female developed sequential bilateral AMN following a single dose of COVISHIELD™ vaccine. On investigations she was found to have a β thalassemia trait. Presentation started unilaterally and progressed to the other eye after a month. On clinical examination, the fundus was apparently normal in both eyes. Significant changes suggestive of AMN were seen on multimodal imaging of the posterior segment of the respective eye at the time of involvement which resolved spontaneously in due course., Conclusion: We report a temporal association of COVID-19 vaccination and AMN.

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To describe a case of herpes simplex virus 1 (HSV 1) infection following coronavirus disease 2019 (COVID-19) vaccination in an Asian Indian female., Methods: Retrospective case report., Result: A 40-year-old female presented with decreased vision, pain, and photophobia of 2 weeks duration. She reported receiving the second dose of COVISHIELD TM (ChAdOx1-S [recombinant]) 1 week prior to the onset of ocular symptoms. Left eye examination revealed granulomatous anterior uveitis. Aqueous sample from the left eye tested positive for HSV1 by polymerase chain reaction(PCR) method. She was managed with oral antiviral therapy, topical steroids, and cycloplegic agent and showed significant improvement of inflammation within 1 week and resolved within 3 weeks., Conclusion: This report demonstrates a potential association of HSV 1 anterior uveitis with COVID-19 vaccination. A high index of suspicion of viral etiology is warranted when uveitis presents with reduced corneal sensations and pigmented keratic precipitates, following a recent history of COVID-19 vaccination.