Baricitinib in COVID-19: a coming-of-age from artificial intelligence to reducing mortality.
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ABSTRACT:
SUBMITTER: Mehta P
PROVIDER: S-EPMC9333997 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
Baricitinib in COVID-19: a coming-of-age from artificial intelligence to reducing mortality.
Mehta Puja P Titanji Boghuma K BK
Lancet (London, England) 20220701 10349
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Project description:Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI) algorithms, to be useful for COVID-19 infection via proposed anti-cytokine effects and as an inhibitor of host cell viral propagation. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID-19 infection. We validated the AI-predicted biochemical inhibitory effects of baricitinib on human numb-associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids. These effects occurred at exposure levels seen clinically. In a case series of patients with bilateral COVID-19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS-CoV-2 viral load, inflammatory markers, and IL-6 levels. Collectively, these data support further evaluation of the anti-cytokine and anti-viral activity of baricitinib and support its assessment in randomized trials in hospitalized COVID-19 patients.
| S-EPMC7300657 | biostudies-literature
Project description:BackgroundThe global demographic situation has been significantly impacted by the COVID-19 pandemic. The objective of this study was to develop a model that predicts the risk of COVID-associated mortality using clinical and laboratory data collected within 72 h of hospital admission.Materials and methodsA total of 3024 subjects with PCR-confirmed COVID-19 were admitted to Almazov National Research Medical Center between May 2020 and August 2021. Among them, 6.25% (n = 189) of patients had a fatal outcome. Five machine learning models and the Boruta-SHAP feature selection method were utilized to assess the risk of mortality during COVID-19 hospitalization.ResultsAll methods demonstrated high efficacy, with ROC AUC (Receiver Operating Characteristic Area Under the Curve) values exceeding 80%. The selected Boruta-SHAP features, when incorporated into the random forest model, achieved an ROC AUC of 93.1% in the validation.ConclusionThroughout the study, close collaboration with healthcare professionals ensured that the developed tool met their practical needs. The success of our model validates the potential of machine learning techniques as decision support systems in clinical practice.
| S-EPMC11456173 | biostudies-literature
Project description:BackgroundCOVID-19 has had a substantial influence on healthcare systems, requiring early prognosis for innovative therapies and optimal results, especially in individuals with comorbidities. AI systems have been used by healthcare practitioners for investigating, anticipating, and predicting diseases, through means including medication development, clinical trial analysis, and pandemic forecasting. This study proposes the use of AI to predict disease severity in terms of hospital mortality among COVID-19 patients.MethodsA cross-sectional study was conducted at King Abdulaziz University, Saudi Arabia. Data were cleaned by encoding categorical variables and replacing missing quantitative values with their mean. The outcome variable, hospital mortality, was labeled as death = 0 or survival = 1, with all baseline investigations, clinical symptoms, and laboratory findings used as predictors. Decision trees, SVM, and random forest algorithms were employed. The training process included splitting the data set into training and testing sets, performing 5-fold cross-validation to tune hyperparameters, and evaluating performance on the test set using accuracy.ResultsThe study assessed the predictive accuracy of outcomes and mortality for COVID-19 patients based on factors such as CRP, LDH, Ferritin, ALP, Bilirubin, D-Dimers, and hospital stay (p-value ≤ 0.05). The analysis revealed that hospital stay, D-Dimers, ALP, Bilirubin, LDH, CRP, and Ferritin significantly influenced hospital mortality (p ≤ 0.0001). The results demonstrated high predictive accuracy, with decision trees achieving 76%, random forest 80%, and support vector machines (SVMs) 82%.ConclusionsArtificial intelligence is a tool crucial for identifying early coronavirus infections and monitoring patient conditions. It improves treatment consistency and decision-making via the development of algorithms.
| S-EPMC11395195 | biostudies-literature
Project description:Drug repurposing or repositioning is a technique whereby existing drugs are used to treat emerging and challenging diseases, including COVID-19. Drug repurposing has become a promising approach because of the opportunity for reduced development timelines and overall costs. In the big data era, artificial intelligence (AI) and network medicine offer cutting-edge application of information science to defining disease, medicine, therapeutics, and identifying targets with the least error. In this Review, we introduce guidelines on how to use AI for accelerating drug repurposing or repositioning, for which AI approaches are not just formidable but are also necessary. We discuss how to use AI models in precision medicine, and as an example, how AI models can accelerate COVID-19 drug repurposing. Rapidly developing, powerful, and innovative AI and network medicine technologies can expedite therapeutic development. This Review provides a strong rationale for using AI-based assistive tools for drug repurposing medications for human disease, including during the COVID-19 pandemic.
| S-EPMC7500917 | biostudies-literature
Project description:Background: Recently, Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has affected more than 200 countries and lead to enormous losses. This study systematically reviews the application of Artificial Intelligence (AI) techniques in COVID-19, especially for diagnosis, estimation of epidemic trends, prognosis, and exploration of effective and safe drugs and vaccines; and discusses the potential limitations. Methods: We report this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase and the Cochrane Library from inception to 19 September 2020 for published studies of AI applications in COVID-19. We used PROBAST (prediction model risk of bias assessment tool) to assess the quality of literature related to the diagnosis and prognosis of COVID-19. We registered the protocol (PROSPERO CRD42020211555). Results: We included 78 studies: 46 articles discussed AI-assisted diagnosis for COVID-19 with total accuracy of 70.00 to 99.92%, sensitivity of 73.00 to 100.00%, specificity of 25 to 100.00%, and area under the curve of 0.732 to 1.000. Fourteen articles evaluated prognosis based on clinical characteristics at hospital admission, such as clinical, laboratory and radiological characteristics, reaching accuracy of 74.4 to 95.20%, sensitivity of 72.8 to 98.00%, specificity of 55 to 96.87% and AUC of 0.66 to 0.997 in predicting critical COVID-19. Nine articles used AI models to predict the epidemic of the COVID-19, such as epidemic peak, infection rate, number of infected cases, transmission laws, and development trend. Eight articles used AI to explore potential effective drugs, primarily through drug repurposing and drug development. Finally, 1 article predicted vaccine targets that have the potential to develop COVID-19 vaccines. Conclusions: In this review, we have shown that AI achieved high performance in diagnosis, prognosis evaluation, epidemic prediction and drug discovery for COVID-19. AI has the potential to enhance significantly existing medical and healthcare system efficiency during the COVID-19 pandemic.
| S-EPMC8514781 | biostudies-literature
Project description:The global pandemic of coronavirus disease (COVID-19) has caused millions of deaths and affected the livelihood of many more people. Early and rapid detection of COVID-19 is a challenging task for the medical community, but it is also crucial in stopping the spread of the SARS-CoV-2 virus. Prior substantiation of artificial intelligence (AI) in various fields of science has encouraged researchers to further address this problem. Various medical imaging modalities including X-ray, computed tomography (CT) and ultrasound (US) using AI techniques have greatly helped to curb the COVID-19 outbreak by assisting with early diagnosis. We carried out a systematic review on state-of-the-art AI techniques applied with X-ray, CT, and US images to detect COVID-19. In this paper, we discuss approaches used by various authors and the significance of these research efforts, the potential challenges, and future trends related to the implementation of an AI system for disease detection during the COVID-19 pandemic.
| S-EPMC8659534 | biostudies-literature
Project description:The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that led to the COVID-19 (Coronavirus Disease 2019) pandemic, has resulted in substantial overburdening of healthcare systems as well as an economic crisis on a global scale. This has in turn resulted in widespread efforts to identify suitable therapies to address this aggressive pathogen. Therapeutic antibody and vaccine development are being actively explored, and a phase I clinical trial of mRNA-1273 which is developed in collaboration between the National Institute of Allergy and Infectious Diseases and Moderna, Inc. is currently underway. Timelines for the broad deployment of a vaccine and antibody therapies have been estimated to be 12-18 months or longer. These are promising approaches that may lead to sustained efficacy in treating COVID-19. However, its emergence has also led to a large number of clinical trials evaluating drug combinations composed of repurposed therapies. As study results of these combinations continue to be evaluated, there is a need to move beyond traditional drug screening and repurposing by harnessing artificial intelligence (AI) to optimize combination therapy design. This may lead to the rapid identification of regimens that mediate unexpected and markedly enhanced treatment outcomes.
| S-EPMC7235485 | biostudies-literature
Project description:This paper provides an early evaluation of Artificial Intelligence (AI) against COVID-19. The main areas where AI can contribute to the fight against COVID-19 are discussed. It is concluded that AI has not yet been impactful against COVID-19. Its use is hampered by a lack of data, and by too much data. Overcoming these constraints will require a careful balance between data privacy and public health, and rigorous human-AI interaction. It is unlikely that these will be addressed in time to be of much help during the present pandemic. In the meantime, extensive gathering of diagnostic data on who is infectious will be essential to save lives, train AI, and limit economic damages.
| S-EPMC7186767 | biostudies-literature
Project description:BackgroundThe ongoing COVID-19 pandemic has caused more than 193,825 deaths during the past few months. A quick-to-be-identified cure for the disease will be a therapeutic medicine that has prior use experiences in patients in order to resolve the current pandemic situation before it could become worsening. Artificial intelligence (AI) technology is hereby applied to identify the marketed drugs with potential for treating COVID-19.MethodsAn AI platform was established to identify potential old drugs with anti-coronavirus activities by using two different learning databases; one consisted of the compounds reported or proven active against SARS-CoV, SARS-CoV-2, human immunodeficiency virus, influenza virus, and the other one containing the known 3C-like protease inhibitors. All AI predicted drugs were then tested for activities against a feline coronavirus in in vitro cell-based assay. These assay results were feedbacks to the AI system for relearning and thus to generate a modified AI model to search for old drugs again.ResultsAfter a few runs of AI learning and prediction processes, the AI system identified 80 marketed drugs with potential. Among them, 8 drugs (bedaquiline, brequinar, celecoxib, clofazimine, conivaptan, gemcitabine, tolcapone, and vismodegib) showed in vitro activities against the proliferation of a feline infectious peritonitis (FIP) virus in Fcwf-4 cells. In addition, 5 other drugs (boceprevir, chloroquine, homoharringtonine, tilorone, and salinomycin) were also found active during the exercises of AI approaches.ConclusionHaving taken advantages of AI, we identified old drugs with activities against FIP coronavirus. Further studies are underway to demonstrate their activities against SARS-CoV-2 in vitro and in vivo at clinically achievable concentrations and doses. With prior use experiences in patients, these old drugs if proven active against SARS-CoV-2 can readily be applied for fighting COVID-19 pandemic.
| S-EPMC7227517 | biostudies-literature
Project description:The genome of the novel coronavirus (COVID-19) disease was first sequenced in January 2020, approximately a month after its emergence in Wuhan, capital of Hubei province, China. COVID-19 genome sequencing is critical to understanding the virus behavior, its origin, how fast it mutates, and for the development of drugs/vaccines and effective preventive strategies. This paper investigates the use of artificial intelligence techniques to learn interesting information from COVID-19 genome sequences. Sequential pattern mining (SPM) is first applied on a computer-understandable corpus of COVID-19 genome sequences to see if interesting hidden patterns can be found, which reveal frequent patterns of nucleotide bases and their relationships with each other. Second, sequence prediction models are applied to the corpus to evaluate if nucleotide base(s) can be predicted from previous ones. Third, for mutation analysis in genome sequences, an algorithm is designed to find the locations in the genome sequences where the nucleotide bases are changed and to calculate the mutation rate. Obtained results suggest that SPM and mutation analysis techniques can reveal interesting information and patterns in COVID-19 genome sequences to examine the evolution and variations in COVID-19 strains respectively.
| S-EPMC7888282 | biostudies-literature