Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings.

BACKGROUND: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. METHODS: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. RESULTS: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. CONCLUSIONS: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

Computational insights into differential interaction of mammalian angiotensin-converting enzyme 2 with the SARS-CoV-2 spike receptor binding domain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Angiotensin-converting enzyme 2 (ACE2) has been identified as the host cell receptor that binds to the receptor-binding domain (RBD) of the SARS-COV-2 spike protein and mediates cell entry. Because the ACE2 proteins are widely available in mammals, it is important to investigate the interactions between the RBD and the ACE2 of other mammals. Here we analyzed the sequences of ACE2 proteins from 16 mammals, predicted the structures of ACE2-RBD complexes by homology modeling, and refined the complexes using molecular dynamics simulation. Analyses on sequence, structure, and dynamics synergistically provide valuable insights into the interactions between ACE2 and RBD. The analysis outcomes suggest that the ACE2 of bovine, cat, and panda form strong binding interactions with RBD, while in the cases of rat, least horseshoe bat, horse, pig, mouse, and civet, the ACE2 proteins interact weakly with RBD.

A robust intelligent zero-day cyber-attack detection technique.

With the introduction of the Internet to the mainstream like e-commerce, online banking, health system and other day-to-day essentials, risk of being exposed to various are increasing exponentially. Zero-day attack(s) targeting unknown vulnerabilities of a software or system opens up further research direction in the field of cyber-attacks. Existing approaches either uses ML/DNN or anomaly-based approach to protect against these attacks. Detecting zero-day attacks through these techniques miss several parameters like frequency of particular byte streams in network traffic and their correlation. Covering attacks that produce lower traffic is difficult through neural network models because it requires higher traffic for correct prediction. This paper proposes a novel robust and intelligent cyber-attack detection model to cover the issues mentioned above using the concept of heavy-hitter and graph technique to detect zero-day attacks. The proposed work consists of two phases (a) Signature generation and (b) Evaluation phase. This model evaluates the performance using generated signatures at the training phase. The result analysis of the proposed zero-day attack detection shows higher performance for accuracy of 91.33% for the binary classification and accuracy of 90.35% for multi-class classification on real-time attack data. The performance against benchmark data set CICIDS18 shows a promising result of 91.62% for binary-class classification on this model. Thus, the proposed approach shows an encouraging result to detect zero-day attacks.

Gendered Work and Barriers in Employment Increase Unjust Work–Life Imbalance for Women: The Need for Structural Responses

As COVID-19 pandemic has disproportionately and negatively impacted women, structural responses are needed to prevent and address work?life imbalance issues experienced by women every day. Gendered work and barriers in gaining employment have reduced women?s participation in paid work/employment. Most of those who are employed, experience unfair work?life imbalance as they end up working for paid job and as well as in their homes. The consequences of COVID-19 pandemic lockdowns have further worsened their work?life imbalance. Most of those who have lost paid jobs have been experiencing significant financial and psychological stress and are doing more work than usual in their homes. To address these issues appropriate structural responses are warranted.

Drug repurposing against SARS-CoV-2 receptor binding domain using ensemble-based virtual screening and molecular dynamics simulations.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused worldwide pandemic and is responsible for millions of worldwide deaths due to -a respiratory disease known as COVID-19. In the search for a cure of COVID-19, drug repurposing is a fast and cost-effective approach to identify anti-COVID-19 drugs from existing drugs. The receptor binding domain (RBD) of the SARS-CoV-2 spike protein has been a main target for drug designs to block spike protein binding to ACE2 proteins. In this study, we probed the conformational plasticity of the RBD using long molecular dynamics (MD) simulations, from which, representative conformations were identified using clustering analysis. Three simulated conformations and the original crystal structure were used to screen FDA approved drugs (2466 drugs) against the predicted binding site at the ACE2-RBD interface, leading to 18 drugs with top docking scores. Notably, 16 out of the 18 drugs were obtained from the simulated conformations, while the crystal structure suggests poor binding. The binding stability of the 18 drugs were further investigated using MD simulations. Encouragingly, 6 drugs exhibited stable binding with RBD at the ACE2-RBD interface and 3 of them (gonadorelin, fondaparinux and atorvastatin) showed significantly enhanced binding after the MD simulations. Our study shows that flexibility modeling of SARS-CoV-2 RBD using MD simulation is of great help in identifying novel agents which might block the interaction between human ACE2 and the SARS-CoV-2 RBD for inhibiting the virus infection.

Prognosticating the Spread of Covid-19 Pandemic Based on Optimal Arima Estimators.

COVID-19 cases have been reported as a global threat and several studies are being conducted using various modelling techniques to evaluate patterns of disease dispersion in the upcoming weeks. Here we propose a simple statistical model that could be used to predict the epidemiological extent of community spread of COVID-19 from the explicit data based on optimal ARIMA model estimators. Raw data was retrieved on confirmed cases of COVID-19 from Johns Hopkins University (https://github.com/CSSEGISandData/COVID-19) and the Auto-Regressive Integrated Moving Average (ARIMA) model was fitted based on cumulative daily figures of confirmed cases aggregated globally for ten major countries to predict their incidence trend. Statistical analysis was completed by using R 3.5.3 software. The optimal ARIMA model having the lowest Akaike information criterion (AIC) value for US (0,2,0); Spain (1,2,0); France (0,2,1); Germany (3,2,2); Iran (1,2,1); China (0,2,1); Russia (3,2,1); India (2,2,2); Australia (1,2,0) and South Africa (0,2,2) imparted the nowcasting of trends for the upcoming weeks. These parameters are (p, d, q) where p refers to the number of autoregressive terms, d refers to the number of times the series has to be differenced before it becomes stationary, and q refers to the number of moving average terms. Results obtained from the ARIMA model showed a significant decrease in cases in Australia; a stable case for China and rising cases have been observed in other countries. This study predicted the possible proliferate of COVID-19, although spreading significantly depends upon the various control and measurement policy taken by each country.