Adverse Effects of COVID-19 Vaccination: Machine Learning and Statistical Approach to Identify and Classify Incidences of Morbidity and Postvaccination Reactogenicity.

Good vaccine safety and reliability are essential for successfully countering infectious disease spread. A small but significant number of adverse reactions to COVID-19 vaccines have been reported. Here, we aim to identify possible common factors in such adverse reactions to enable strategies that reduce the incidence of such reactions by using patient data to classify and characterise those at risk. We examined patient medical histories and data documenting postvaccination effects and outcomes. The data analyses were conducted using a range of statistical approaches followed by a series of machine learning classification algorithms. In most cases, a group of similar features was significantly associated with poor patient reactions. These included patient prior illnesses, admission to hospitals and SARS-CoV-2 reinfection. The analyses indicated that patient age, gender, taking other medications, type-2 diabetes, hypertension, allergic history and heart disease are the most significant pre-existing factors associated with the risk of poor outcome. In addition, long duration of hospital treatments, dyspnoea, various kinds of pain, headache, cough, asthenia, and physical disability were the most significant clinical predictors. The machine learning classifiers that are trained with medical history were also able to predict patients with complication-free vaccination and have an accuracy score above 90%. Our study identifies profiles of individuals that may need extra monitoring and care (e.g., vaccination at a location with access to comprehensive clinical support) to reduce negative outcomes through classification approaches.

A deep learning approach using effective preprocessing techniques to detect COVID-19 from chest CT-scan and X-ray images.

Coronavirus disease-19 (COVID-19) is a severe respiratory viral disease first reported in late 2019 that has spread worldwide. Although some wealthy countries have made significant progress in detecting and containing this disease, most underdeveloped countries are still struggling to identify COVID-19 cases in large populations. With the rising number of COVID-19 cases, there are often insufficient COVID-19 diagnostic kits and related resources in such countries. However, other basic diagnostic resources often do exist, which motivated us to develop Deep Learning models to assist clinicians and radiologists to provide prompt diagnostic support to the patients. In this study, we have developed a deep learning-based COVID-19 case detection model trained with a dataset consisting of chest CT scans and X-ray images. A modified ResNet50V2 architecture was employed as deep learning architecture in the proposed model. The dataset utilized to train the model was collected from various publicly available sources and included four class labels: confirmed COVID-19, normal controls and confirmed viral and bacterial pneumonia cases. The aggregated dataset was preprocessed through a sharpening filter before feeding the dataset into the proposed model. This model attained an accuracy of 96.452% for four-class cases (COVID-19/Normal/Bacterial pneumonia/Viral pneumonia), 97.242% for three-class cases (COVID-19/Normal/Bacterial pneumonia) and 98.954% for two-class cases (COVID-19/Viral pneumonia) using chest X-ray images. The model acquired a comprehensive accuracy of 99.012% for three-class cases (COVID-19/Normal/Community-acquired pneumonia) and 99.99% for two-class cases (Normal/COVID-19) using CT-scan images of the chest. This high accuracy presents a new and potentially important resource to enable radiologists to identify and rapidly diagnose COVID-19 cases with only basic but widely available equipment.

Diseasome and comorbidities complexities of SARS-CoV-2 infection with common malignant diseases.

With the increasing number of immunoinflammatory complexities, cancer patients have a higher risk of serious disease outcomes and mortality with SARS-CoV-2 infection which is still not clear. In this study, we aimed to identify infectome, diseasome and comorbidities between COVID-19 and cancer via comprehensive bioinformatics analysis to identify the synergistic severity of the cancer patient for SARS-CoV-2 infection. We utilized transcriptomic datasets of SARS-CoV-2 and different cancers from Gene Expression Omnibus and Array Express Database to develop a bioinformatics pipeline and software tools to analyze a large set of transcriptomic data and identify the pathobiological relationships between the disease conditions. Our bioinformatics approach revealed commonly dysregulated genes (MARCO, VCAN, ACTB, LGALS1, HMOX1, TIMP1, OAS2, GAPDH, MSH3, FN1, NPC2, JUND, CHI3L1, GPNMB, SYTL2, CASP1, S100A8, MYO10, IGFBP3, APCDD1, COL6A3, FABP5, PRDX3, CLEC1B, DDIT4, CXCL10 and CXCL8), common gene ontology (GO), molecular pathways between SARS-CoV-2 infections and cancers. This work also shows the synergistic complexities of SARS-CoV-2 infections for cancer patients through the gene set enrichment and semantic similarity. These results highlighted the immune systems, cell activation and cytokine production GO pathways that were observed in SARS-CoV-2 infections as well as breast, lungs, colon, kidney and thyroid cancers. This work also revealed ribosome biogenesis, wnt signaling pathway, ribosome, chemokine and cytokine pathways that are commonly deregulated in cancers and COVID-19. Thus, our bioinformatics approach and tools revealed interconnections in terms of significant genes, GO, pathways between SARS-CoV-2 infections and malignant tumors.

Bioinformatics and system biology approach to identify the influences of COVID-19 on cardiovascular and hypertensive comorbidities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals that have hypertension or cardiovascular comorbidities have an elevated risk of serious coronavirus disease 2019 (COVID-19) disease and high rates of mortality but how COVID-$19$ and cardiovascular diseases interact are unclear. We therefore sought to identify novel mechanisms of interaction by identifying genes with altered expression in SARS-CoV-$2$ infection that are relevant to the pathogenesis of cardiovascular disease and hypertension. Some recent research shows the SARS-CoV-$2$ uses the angiotensin converting enzyme-$2$ (ACE-$2$) as a receptor to infect human susceptible cells. The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. ACE2 usually converts Angiotensin I in the renin-angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE-$2$, although there are claims that such medications actually reduce lung injury caused by COVID-$19$. We employed bioinformatics and systematic approaches to identify such genetic links, using messenger RNA data peripheral blood cells from COVID-$19$ patients and compared them with blood samples from patients with either chronic heart failure disease or hypertensive diseases. We have also considered the immune response genes with elevated expression in COVID-$19$ to those active in cardiovascular diseases and hypertension. Differentially expressed genes (DEGs) common to COVID-$19$ and chronic heart failure, and common to COVID-$19$ and hypertension, were identified; the involvement of these common genes in the signalling pathways and ontologies studied. COVID-$19$ does not share a large number of differentially expressed genes with the conditions under consideration. However, those that were identified included genes playing roles in T cell functions, toll-like receptor pathways, cytokines, chemokines, cell stress, type 2 diabetes and gastric cancer. We also identified protein-protein interactions, gene regulatory networks and suggested drug and chemical compound interactions using the differentially expressed genes. The result of this study may help in identifying significant targets of treatment that can combat the ongoing pandemic due to SARS-CoV-$2$ infection.

Gene expression profiling of SARS-CoV-2 infections reveal distinct primary lung cell and systemic immune infection responses that identify pathways relevant in COVID-19 disease.

To identify key gene expression pathways altered with infection of the novel coronavirus SARS-CoV-2, we performed the largest comparative genomic and transcriptomic analysis to date. We compared the novel pandemic coronavirus SARS-CoV-2 with SARS-CoV and MERS-CoV, as well as influenza A strains H1N1, H3N2 and H5N1. Phylogenetic analysis confirms that SARS-CoV-2 is closely related to SARS-CoV at the level of the viral genome. RNAseq analyses demonstrate that human lung epithelial cell responses to SARS-CoV-2 infection are distinct. Extensive Gene Expression Omnibus literature screening and drug predictive analyses show that SARS-CoV-2 infection response pathways are closely related to those of SARS-CoV and respiratory syncytial virus infections. We validated SARS-CoV-2 infection response genes as disease-associated using Kaplan-Meier survival estimates in lung disease patient data. We also analysed COVID-19 patient peripheral blood samples, which identified signalling pathway concordance between the primary lung cell and blood cell infection responses.

Machine Learning Approaches to Identify Patient Comorbidities and Symptoms That Increased Risk of Mortality in COVID-19.

Providing appropriate care for people suffering from COVID-19, the disease caused by the pandemic SARS-CoV-2 virus, is a significant global challenge. Many individuals who become infected may have pre-existing conditions that may interact with COVID-19 to increase symptom severity and mortality risk. COVID-19 patient comorbidities are likely to be informative regarding the individual risk of severe illness and mortality. Determining the degree to which comorbidities are associated with severe symptoms and mortality would thus greatly assist in COVID-19 care planning and provision. To assess this we performed a meta-analysis of published global literature, and machine learning predictive analysis using an aggregated COVID-19 global dataset. Our meta-analysis suggested that chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CEVD), cardiovascular disease (CVD), type 2 diabetes, malignancy, and hypertension as most significantly associated with COVID-19 severity in the current published literature. Machine learning classification using novel aggregated cohort data similarly found COPD, CVD, CKD, type 2 diabetes, malignancy, and hypertension, as well as asthma, as the most significant features for classifying those deceased versus those who survived COVID-19. While age and gender were the most significant predictors of mortality, in terms of symptom-comorbidity combinations, it was observed that Pneumonia-Hypertension, Pneumonia-Diabetes, and Acute Respiratory Distress Syndrome (ARDS)-Hypertension showed the most significant associations with COVID-19 mortality. These results highlight the patient cohorts most likely to be at risk of COVID-19-related severe morbidity and mortality, which have implications for prioritization of hospital resources.

Transcriptomic studies revealed pathophysiological impact of COVID-19 to predominant health conditions.

Despite the association of prevalent health conditions with coronavirus disease 2019 (COVID-19) severity, the disease-modifying biomolecules and their pathogenetic mechanisms remain unclear. This study aimed to understand the influences of COVID-19 on different comorbidities and vice versa through network-based gene expression analyses. Using the shared dysregulated genes, we identified key genetic determinants and signaling pathways that may involve in their shared pathogenesis. The COVID-19 showed significant upregulation of 93 genes and downregulation of 15 genes. Interestingly, it shares 28, 17, 6 and 7 genes with diabetes mellitus (DM), lung cancer (LC), myocardial infarction and hypertension, respectively. Importantly, COVID-19 shared three upregulated genes (i.e. MX2, IRF7 and ADAM8) with DM and LC. Conversely, downregulation of two genes (i.e. PPARGC1A and METTL7A) was found in COVID-19 and LC. Besides, most of the shared pathways were related to inflammatory responses. Furthermore, we identified six potential biomarkers and several important regulatory factors, e.g. transcription factors and microRNAs, while notable drug candidates included captopril, rilonacept and canakinumab. Moreover, prognostic analysis suggests concomitant COVID-19 may result in poor outcome of LC patients. This study provides the molecular basis and routes of the COVID-19 progression due to comorbidities. We believe these findings might be useful to further understand the intricate association of these diseases as well as for the therapeutic development.

Short-Term Prediction of COVID-19 Cases Using Machine Learning Models

The first case in Bangladesh of the novel coronavirus disease (COVID-19) was reported on 8 March 2020, with the number of confirmed cases rapidly rising to over 175,000 by July 2020. In the absence of effective treatment, an essential tool of health policy is the modeling and forecasting of the progress of the pandemic. We, therefore, developed a cloud-based machine learning short-term forecasting model for Bangladesh, in which several regression-based machine learning models were applied to infected case data to estimate the number of COVID-19-infected people over the following seven days. This approach can accurately forecast the number of infected cases daily by training the prior 25 days sample data recorded on our web application. The outcomes of these efforts could aid the development and assessment of prevention strategies and identify factors that most affect the spread of COVID-19 infection in Bangladesh.

TClustVID: A novel machine learning classification model to investigate topics and sentiment in COVID-19 tweets.

COVID-19, caused by SARS-CoV2 infection, varies greatly in its severity but presents with serious respiratory symptoms with vascular and other complications, particularly in older adults. The disease can be spread by both symptomatic and asymptomatic infected individuals. Uncertainty remains over key aspects of the virus infectiousness (particularly the newly emerging variants) and the disease has had severe economic impacts globally. For these reasons, COVID-19 is the subject of intense and widespread discussion on social media platforms including Facebook and Twitter. These public forums substantially influence public opinions and in some cases can exacerbate the widespread panic and misinformation spread during the crisis. Thus, this work aimed to design an intelligent clustering-based classification and topic extracting model named TClustVID that analyzes COVID-19-related public tweets to extract significant sentiments with high accuracy. We gathered COVID-19 Twitter datasets from the IEEE Dataport repository and employed a range of data preprocessing methods to clean the raw data, then applied tokenization and produced a word-to-index dictionary. Thereafter, different classifications were employed on these datasets which enabled the exploration of the performance of traditional classification and TClustVID. Our analysis found that TClustVID showed higher performance compared to traditional methodologies that are determined by clustering criteria. Finally, we extracted significant topics from the clusters, split them into positive, neutral and negative sentiments, and identified the most frequent topics using the proposed model. This approach is able to rapidly identify commonly prevailing aspects of public opinions and attitudes related to COVID-19 and infection prevention strategies spreading among different populations.

COVID-19 patient transcriptomic and genomic profiling reveals comorbidity interactions with psychiatric disorders.

Psychiatric symptoms are seen in some COVID-19 patients, as direct or indirect sequelae, but it is unclear whether SARS-CoV-2 infection interacts with underlying neuronal or psychiatric susceptibilities. Such interactions might arise from COVID-19 immune responses, from infection of neurons themselves or may reflect social-psychological causes. To clarify this we sought the key gene expression pathways altered in COVID-19 also affected in bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia, since this may identify pathways of interaction that could be treatment targets. We performed large scale comparisons of whole transcriptome data and immune factor transcript data in peripheral blood mononuclear cells (PBMC) from COVID-19 patients and patients with psychiatric disorders. We also analysed genome-wide association study (GWAS) data for symptomatic COVID-19 patients, comparing GWAS and whole-genome sequence data from patients with bipolar disorder, PTSD and schizophrenia patients. These studies revealed altered signalling and ontology pathways shared by COVID-19 patients and the three psychiatric disorders. Finally, co-expression and network analyses identified gene clusters common to the conditions. COVID-19 patients had peripheral blood immune system profiles that overlapped with those of patients with psychiatric conditions. From the pathways identified, PTSD profiles were the most highly correlated with COVID-19, perhaps consistent with stress-immune system interactions seen in PTSD. We also revealed common inflammatory pathways that may exacerbate psychiatric disorders, which may support the usage of anti-inflammatory medications in these patients. It also highlights the potential clinical application of multi-level dataset studies in difficult-to-treat psychiatric disorders in this COVID-19 pandemic.

A machine learning model to identify early stage symptoms of SARS-Cov-2 infected patients.

The recent outbreak of the respiratory ailment COVID-19 caused by novel coronavirus SARS-Cov2 is a severe and urgent global concern. In the absence of effective treatments, the main containment strategy is to reduce the contagion by the isolation of infected individuals; however, isolation of unaffected individuals is highly undesirable. To help make rapid decisions on treatment and isolation needs, it would be useful to determine which features presented by suspected infection cases are the best predictors of a positive diagnosis. This can be done by analyzing patient characteristics, case trajectory, comorbidities, symptoms, diagnosis, and outcomes. We developed a model that employed supervised machine learning algorithms to identify the presentation features predicting COVID-19 disease diagnoses with high accuracy. Features examined included details of the individuals concerned, e.g., age, gender, observation of fever, history of travel, and clinical details such as the severity of cough and incidence of lung infection. We implemented and applied several machine learning algorithms to our collected data and found that the XGBoost algorithm performed with the highest accuracy (>85%) to predict and select features that correctly indicate COVID-19 status for all age groups. Statistical analyses revealed that the most frequent and significant predictive symptoms are fever (41.1%), cough (30.3%), lung infection (13.1%) and runny nose (8.43%). While 54.4% of people examined did not develop any symptoms that could be used for diagnosis, our work indicates that for the remainder, our predictive model could significantly improve the prediction of COVID-19 status, including at early stages of infection.