Clinical Characteristics and Outcomes of Severe or Critical COVID-19 Patients Presenting No Respiratory Symptoms or Fever at Onset

It is difficult to identify suspected cases of atypical patients with coronavirus disease 2019 (COVID-19), and data on severe or critical patients are scanty. This retrospective study presents the clinical, laboratory, and radiological profiles, treatments, and outcomes of atypical COVID-19 patients without respiratory symptoms or fever at onset. The study examined ten atypical patients out of 909 severe or critical patients diagnosed with COVID-19 in Wuhan Union Hospital West Campus between 25 January 2020 and 10 February 2020. Data were obtained from the electronic medical records of severe or critical patients without respiratory symptoms or fever at onset. Outcomes were followed up to discharge or death. Among 943 COVID-19 patients, 909 (96.4%) were severe or critical type. Of the severe or critical patients, ten (1.1%) presented without respiratory symptoms or fever at admission. The median age of the ten participants was 63 years (interquartile range (IQR): 57–72), and seven participants were men. The median time from symptom onset to admission was 14 d (IQR: 7–20). Eight of the ten patients had chronic diseases. The patients had fatigue (n = 5), headache or dizziness (n = 4), diarrhea (n = 5), anorexia (n = 3), nausea or vomiting (n = 3), and eye discomfort (n = 1). Four patients were found to have lymphopenia. Imaging examination revealed that nine patients had bilateral pneumonia and one had unilateral pneumonia. Eventually, two patients died and eight were discharged. In the discharged patients, the median time from admission to discharge lasted 24 d (IQR: 13–43). In summary, some severe or critical COVID-19 patients were found to have no respiratory symptoms or fever at onset. All such atypical cases should be identified and quarantined as early as possible, since they tend to have a prolonged hospital stay or fatal outcomes. Chest computed tomography (CT) scan and nucleic acid detection should be performed immediately on close contacts of COVID-19 patients to screen out those with atypical infections, even if the contacts present without respiratory symptoms or fever at onset.     

Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study

Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (≥ 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs 31.2%), coronary heart disease (17.1% vs 8.0%), and chronic kidney diseases (6.2% vs 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol·L⁻¹ (interquartile range (IQR): 5.80–9.29) vs 5.46 mmol·L⁻¹ (IQR: 5.00–6.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol·L⁻¹ (IQR: 1.67–2.76) vs 1.75 mmol·L⁻¹ (IQR: 1.27–2.01)), and systolic pressure (130 mmHg (IQR: 120–142) vs 122 mmHg (IQR: 110–137)) (1 mmHg = 133.3 Pa) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.     

The economic value of quarantine is higher at lower case prevalence,with quarantine justified at lower risk of infection

Some infectious diseases, such as COVID-19 or the influenza pandemic of 1918, are so harmful that they justify broad-scale social distancing. Targeted quarantine can reduce the amount of indiscriminate social distancing needed to control transmission. Finding the optimal balance between targeted versus broad-scale policies can be operationalized by minimizing the total amount of social isolation needed to achieve a target reproductive number. Optimality is achieved by quarantining on the basis of a risk threshold that depends strongly on current disease prevalence, suggesting that very different disease control policies should be used at different times or places. Aggressive quarantine is warranted given low disease prevalence, while populations with a higher base rate of infection should rely more on social distancing by all. The total value of a quarantine policy rises as case counts fall, is relatively insensitive to vaccination unless the vaccinated are exempt from distancing policies, and is substantially increased by the availability of modestly more information about individual risk of infectiousness.     

Bayesian Rule Modeling for Interpretable Mortality Classification of COVID-19 Patients

Coronavirus disease 2019 (COVID-19) has been termed a “Pandemic Disease” that has infected many people and caused many deaths on a nearly unprecedented level. As more people are infected each day, it continues to pose a serious threat to humanity worldwide. As a result, healthcare systems around the world are facing a shortage of medical space such as wards and sickbeds. In most cases, healthy people experience tolerable symptoms if they are infected. However, in other cases, patients may suffer severe symptoms and require treatment in an intensive care unit. Thus, hospitals should select patients who have a high risk of death and treat them first. To solve this problem, a number of models have been developed for mortality prediction. However, they lack interpretability and generalization. To prepare a model that addresses these issues, we proposed a COVID-19 mortality prediction model that could provide new insights. We identified blood factors that could affect the prediction of COVID-19 mortality. In particular, we focused on dependency reduction using partial correlation and mutual information. Next, we used the Class-Attribute Interdependency Maximization (CAIM) algorithm to bin continuous values. Then, we used Jensen Shannon Divergence (JSD) and Bayesian posterior probability to create less redundant and more accurate rules. We provided a ruleset with its own posterior probability as a result. The extracted rules are in the form of “if antecedent then results, posterior probability()”. If the sample matches the extracted rules, then the result is positive. The average AUC Score was 96.77% for the validation dataset and the F1-score was 92.8% for the test data. Compared to the results of previous studies, it shows good performance in terms of classification performance, generalization, and interpretability.     

Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019: A Pilot Randomized Controlled Trial

No therapeutics have been proven effective yet for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the efficacy and safety of Triazavirin therapy for COVID-19, we conducted a randomized, double-blinded controlled trial involving hospitalized adult patients with COVID-19. Participants were enrolled from ten sites, and were randomized into two arms of the study with a ratio of 1:1. Patients were treated with Triazavirin 250 mg versus a placebo three or four times a day for 7 d. The primary outcome was set as the time to clinical improvement, defined as normalization of body temperature, respiratory rate, oxygen saturation, cough, and absorption of pulmonary infection by chest computed tomography (CT) until 28 d after randomization. Secondary outcomes included individual components of the primary outcome, the mean time and proportion of inflammatory absorption in the lung, and the conversion rate to a repeated negative SARS-CoV-2 nucleic acid test of throat swab sampling. Concomitant therapeutic treatments, adverse events, and serious adverse events were recorded. Our study was halted after the recruitment of 52 patients, since the number of new infections in the participating hospitals decreased greatly. We randomized 52 patients for treatment with Triazavirin (n = 26) or a placebo (n = 26). We found no differences in the time to clinical improvement (median, 7 d versus 12 d; risk ratio (RR), 2.0; 95% confidence interval (CI), 0.7–5.6; p = 0.2), with clinical improvement occurring in ten patients in the Triazavirin group and six patients in the placebo group (38.5% versus 23.1%; RR, 2.1; 95% CI, 0.6–7.0; p = 0.2). All components of the primary outcome normalized within 28 d, with the exception of absorption of pulmonary infection (Triazavirin 50.0%, placebo 26.1%). Patients in the Triazavirin group used less frequent concomitant therapies for respiratory, cardiac, renal, hepatic, or coagulation supports. Although no statistically significant evidence was found to indicate that Triazavirin benefits COVID-19 patients, our observations indicated possible benefits from its use to treat COVID-19 due to its antiviral effects. Further study is required for confirmation.     

Inference of COVID-19 epidemiological distributions from Brazilian hospital data

Knowing COVID-19 epidemiological distributions, such as the time from patient admission to death, is directly relevant to effective primary and secondary care planning, and moreover, the mathematical modelling of the pandemic generally. We determine epidemiological distributions for patients hospitalized with COVID-19 using a large dataset (N = 21 000 − 157 000) from the Brazilian Sistema de Informação de Vigilância Epidemiológica da Gripe database. A joint Bayesian subnational model with partial pooling is used to simultaneously describe the 26 states and one federal district of Brazil, and shows significant variation in the mean of the symptom-onset-to-death time, with ranges between 11.2 and 17.8 days across the different states, and a mean of 15.2 days for Brazil. We find strong evidence in favour of specific probability density function choices: for example, the gamma distribution gives the best fit for onset-to-death and the generalized lognormal for onset-to-hospital-admission. Our results show that epidemiological distributions have considerable geographical variation, and provide the first estimates of these distributions in a low and middle-income setting. At the subnational level, variation in COVID-19 outcome timings are found to be correlated with poverty, deprivation and segregation levels, and weaker correlation is observed for mean age, wealth and urbanicity.     

Early COVID-19 Symptoms Identification Using Hybrid Unsupervised Machine Learning Techniques

The COVID-19 virus exhibits pneumonia-like symptoms, including fever, cough, and shortness of breath, and may be fatal. Many COVID-19 contraction experiments require comprehensive clinical procedures at medical facilities. Clinical studies help to make a correct diagnosis of COVID-19, where the disease has already spread to the organs in most cases. Prompt and early diagnosis is indispensable for providing patients with the possibility of early clinical diagnosis and slowing down the disease spread. Therefore, clinical investigations in patients with COVID-19 have revealed distinct patterns of breathing relative to other diseases such as flu and cold, which are worth investigating. Current supervised Machine Learning (ML) based techniques mostly investigate clinical reports such as X-Rays and Computerized Tomography (CT) for disease detection. This strategy relies on a larger clinical dataset and does not focus on early symptom identification. Towards this end, an innovative hybrid unsupervised ML technique is introduced to uncover the probability of COVID-19 occurrence based on the breathing patterns and commonly reported symptoms, fever, and cough. Specifically, various metrics, including body temperature, breathing and cough patterns, and physical activity, were considered in this study. Finally, a lightweight ML algorithm based on the K-Means and Isolation Forest technique was implemented on relatively small data including 40 individuals. The proposed technique shows an outlier detection with an accuracy of 89%, on average.     

Technology Landscape for Epidemiological Prediction and Diagnosis of COVID-19

The COVID-19 outbreak initiated from the Chinese city of Wuhan and eventually affected almost every nation around the globe. From China, the disease started spreading to the rest of the world. After China, Italy became the next epicentre of the virus and witnessed a very high death toll. Soon nations like the USA became severely hit by SARS-CoV-2 virus. The World Health Organisation, on 11th March 2020, declared COVID-19 a pandemic. To combat the epidemic, the nations from every corner of the world has instituted various policies like physical distancing, isolation of infected population and researching on the potential vaccine of SARS-CoV-2. To identify the impact of various policies implemented by the affected countries on the pandemic spread, a myriad of AI-based models have been presented to analyse and predict the epidemiological trends of COVID-19. In this work, the authors present a detailed study of different artificial intelligence frameworks applied for predictive analysis of COVID-19 patient record. The forecasting models acquire information from records to detect the pandemic spreading and thus enabling an opportunity to take immediate actions to reduce the spread of the virus. This paper addresses the research issues and corresponding solutions associated with the prediction and detection of infectious diseases like COVID-19. It further focuses on the study of vaccinations to cope with the pandemic. Finally, the research challenges in terms of data availability, reliability, the accuracy of the existing prediction models and other open issues are discussed to outline the future course of this study.     

Beyond R0: heterogeneity in secondary infections and probabilistic epidemic forecasting

The basic reproductive number, R₀, is one of the most common and most commonly misapplied numbers in public health. Often used to compare outbreaks and forecast pandemic risk, this single number belies the complexity that different epidemics can exhibit, even when they have the same R₀. Here, we reformulate and extend a classic result from random network theory to forecast the size of an epidemic using estimates of the distribution of secondary infections, leveraging both its average R₀ and the underlying heterogeneity. Importantly, epidemics with lower R₀ can be larger if they spread more homogeneously (and are therefore more robust to stochastic fluctuations). We illustrate the potential of this approach using different real epidemics with known estimates for R₀, heterogeneity and epidemic size in the absence of significant intervention. Further, we discuss the different ways in which this framework can be implemented in the data-scarce reality of emerging pathogens. Lastly, we demonstrate that without data on the heterogeneity in secondary infections for emerging infectious diseases like COVID-19 the uncertainty in outbreak size ranges dramatically. Taken together, our work highlights the critical need for contact tracing during emerging infectious disease outbreaks and the need to look beyond R₀.     

Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications

The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide efforts to understand the biological traits of the newly identified human coronavirus (HCoV-19) virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 spike protein (S protein), 20 are completely occupied by N-glycans, predominantly of the oligomannose type. All seven glycosylation sites in human angiotensin I converting enzyme 2 (hACE2) were found to be completely occupied, mainly by complex N-glycans. However, glycosylation did not directly contribute to the binding affinity between HCoV-19 S protein and hACE2. Additional post-translational modification (PTM) was identified, including multiple methylated sites in both proteins and multiple sites with hydroxylproline in hACE2. Refined structural models of HCoV-19 S protein and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy structures. The PTM and glycan maps of HCoV-19 S protein and hACE2 provide additional structural details for studying the mechanisms underlying host attachment and the immune response of HCoV-19, as well as knowledge for developing desperately needed remedies and vaccines.     

Pandemic Analysis and Prediction of COVID-19 Using Gaussian Doubling Times

COVID-19 has become a pandemic, with cases all over the world, with widespread disruption in some countries, such as Italy, US, India, South Korea, and Japan. Early and reliable detection of COVID-19 is mandatory to control the spread of infection. Moreover, prediction of COVID-19 spread in near future is also crucial to better plan for the disease control. For this purpose, we proposed a robust framework for the analysis, prediction, and detection of COVID-19. We make reliable estimates on key pandemic parameters and make predictions on the point of inflection and possible washout time for various countries around the world. The estimates, analysis and predictions are based on the data gathered from Johns Hopkins Center during the time span of April 21 to June 27, 2020. We use the normal distribution for simple and quick predictions of the coronavirus pandemic model and estimate the parameters of Gaussian curves using the least square parameter curve fitting for several countries in different continents. The predictions rely on the possible outcomes of Gaussian time evolution with the central limit theorem of statistics the predictions to be well justified. The parameters of Gaussian distribution, i.e., maximum time and width, are determined through a statistical χ2-fit for the purpose of doubling times after April 21, 2020. For COVID-19 detection, we proposed a novel method based on the Histogram of Oriented Gradients (HOG) and CNN in multi-class classification scenario i.e., Normal, COVID-19, viral pneumonia etc. Experimental results show the effectiveness of our framework for reliable prediction and detection of COVID-19.     

Infection,inflammation and intervention: mechanistic modelling of epithelial cells in COVID-19

While the pathological mechanisms in COVID-19 illness are still poorly understood, it is increasingly clear that high levels of pro-inflammatory mediators play a major role in clinical deterioration in patients with severe disease. Current evidence points to a hyperinflammatory state as the driver of respiratory compromise in severe COVID-19 disease, with a clinical trajectory resembling acute respiratory distress syndrome, but how this ‘runaway train’ inflammatory response emerges and is maintained is not known. Here, we present the first mathematical model of lung hyperinflammation due to SARS-CoV-2 infection. This model is based on a network of purported mechanistic and physiological pathways linking together five distinct biochemical species involved in the inflammatory response. Simulations of our model give rise to distinct qualitative classes of COVID-19 patients: (i) individuals who naturally clear the virus, (ii) asymptomatic carriers and (iii–v) individuals who develop a case of mild, moderate, or severe illness. These findings, supported by a comprehensive sensitivity analysis, point to potential therapeutic interventions to prevent the emergence of hyperinflammation. Specifically, we suggest that early intervention with a locally acting anti-inflammatory agent (such as inhaled corticosteroids) may effectively blockade the pathological hyperinflammatory reaction as it emerges.     

Prediction of COVID-19 Cases Using Machine Learning for Effective Public Health Management

COVID-19 is a pandemic that has affected nearly every country in the world. At present, sustainable development in the area of public health is considered vital to securing a promising and prosperous future for humans. However, widespread diseases, such as COVID-19, create numerous challenges to this goal, and some of those challenges are not yet defined. In this study, a Shallow Single-Layer Perceptron Neural Network (SSLPNN) and Gaussian Process Regression (GPR) model were used for the classification and prediction of confirmed COVID-19 cases in five geographically distributed regions of Asia with diverse settings and environmental conditions: namely, China, South Korea, Japan, Saudi Arabia, and Pakistan. Significant environmental and non-environmental features were taken as the input dataset, and confirmed COVID-19 cases were taken as the output dataset. A correlation analysis was done to identify patterns in the cases related to fluctuations in the associated variables. The results of this study established that the population and air quality index of a region had a statistically significant influence on the cases. However, age and the human development index had a negative influence on the cases. The proposed SSLPNN-based classification model performed well when predicting the classes of confirmed cases. During training, the binary classification model was highly accurate, with a Root Mean Square Error (RMSE) of 0.91. Likewise, the results of the regression analysis using the GPR technique with Matern 5/2 were highly accurate (RMSE = 0.95239) when predicting the number of confirmed COVID-19 cases in an area. However, dynamic management has occupied a core place in studies on the sustainable development of public health but dynamic management depends on proactive strategies based on statistically verified approaches, like Artificial Intelligence (AI). In this study, an SSLPNN model has been trained to fit public health associated data into an appropriate class, allowing GPR to predict the number of confirmed COVID-19 cases in an area based on the given values of selected parameters. Therefore, this tool can help authorities in different ecological settings effectively manage COVID-19.     

Policy innovation and emergence of innovative health technology: The system dynamics modelling of early COVID-19 handling in Indonesia

This article examines policy innovation, emergence of innovative health technology and its implication for a health system. The complexity of policy innovation implementation resulting from mixing public health resolution and economic interest will trigger the emergence of innovative health technology, which implies a health system improvement. The findings revealed that: First, policy innovation based on a science-mix category created the complexity of policy enforcement, affected the scale and speed of COVID-19 transmissions, and triggered the emergence of health innovative technology. Second, despite policy innovation in early COVID-19, handling was relatively less successful due to restricting factors in policy implementation but provided a new market for the emergence of innovative health technology. Third, the emergence of innovative health technology has strengthened health system preparedness during the pandemic, and provide an opportunity to re-examine the strengths and deficiencies of an entire health system for better health care.     

Automatic Detection of COVID-19 Using Chest X-Ray Images and Modified ResNet18-Based Convolution Neural Networks

The latest studies with radiological imaging techniques indicate that X-ray images provide valuable details on the Coronavirus disease 2019 (COVID-19). The usage of sophisticated artificial intelligence technology (AI) and the radiological images can help in diagnosing the disease reliably and addressing the problem of the shortage of trained doctors in remote villages. In this research, the automated diagnosis of Coronavirus disease was performed using a dataset of X-ray images of patients with severe bacterial pneumonia, reported COVID-19 disease, and normal cases. The goal of the study is to analyze the achievements for medical image recognition of state-of-the-art neural networking architectures. Transfer Learning technique has been implemented in this work. Transfer learning is an ambitious task, but it results in impressive outcomes for identifying distinct patterns in tiny datasets of medical images. The findings indicate that deep learning with X-ray imagery could retrieve important biomarkers relevant for COVID-19 disease detection. Since all diagnostic measures show failure levels that pose questions, the scientific profession should determine the probability of integration of X-rays with the clinical treatment, utilizing the results. The proposed model achieved 96.73% accuracy outperforming the ResNet50 and traditional Resnet18 models. Based on our findings, the proposed system can help the specialist doctors in making verdicts for COVID-19 detection.     

Modelling the Psychological Impact of COVID-19 in Saudi Arabia Using Machine Learning

This article aims to assess health habits, safety behaviors, and anxiety factors in the community during the novel coronavirus disease (COVID-19) pandemic in Saudi Arabia based on primary data collected through a questionnaire with 320 respondents. In other words, this paper aims to provide empirical insights into the correlation and the correspondence between socio-demographic factors (gender, nationality, age, citizenship factors, income, and education), and psycho-behavioral effects on individuals in response to the emergence of this new pandemic. To focus on the interaction between these variables and their effects, we suggest different methods of analysis, comprising regression trees and support vector machine regression (SVMR) algorithms. According to the regression tree results, the age variable plays a predominant role in health habits, safety behaviors, and anxiety. The health habit index, which focuses on the extent of behavioral change toward the commitment to use the health and protection methods, is highly affected by gender and age factors. The average monthly income is also a relevant factor but has contrasting effects during the COVID-19 pandemic period. The results of the SVMR model reveal a strong positive effect of income, with R² values of 99.59%, 99.93% and 99.88% corresponding to health habits, safety behaviors, and anxiety.     

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes has been named coronavirus disease 2019 (COVID-19). More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was 1%–2%. No specific treatment has been reported. Herein, we examined the effects of favipiravir (FPV) versus lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million international unit (IU) twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million IU twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance median time was found for the FPV arm versus the control arm (4 d (interquartile range (IQR): 2.5–9) versus 11 d (IQR: 8–13), P < 0.001). The FPV arm also showed significant improvement in chest CT compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest CT. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.