Coordinating virus research: The Virus Infectious Disease Ontology.

The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Rapid, accurate, and consistent interpretation of generated data is thereby of fundamental concern. Ontologies-structured, controlled, vocabularies-are designed to support consistency of interpretation, and thereby to prevent the development of data silos. This paper describes how ontologies are serving this purpose in the COVID-19 research domain, by following principles of the Open Biological and Biomedical Ontology (OBO) Foundry and by reusing existing ontologies such as the Infectious Disease Ontology (IDO) Core, which provides terminological content common to investigations of all infectious diseases. We report here on the development of an IDO extension, the Virus Infectious Disease Ontology (VIDO), a reference ontology covering viral infectious diseases. We motivate term and definition choices, showcase reuse of terms from existing OBO ontologies, illustrate how ontological decisions were motivated by relevant life science research, and connect VIDO to the Coronavirus Infectious Disease Ontology (CIDO). We next use terms from these ontologies to annotate selections from life science research on SARS-CoV-2, highlighting how ontologies employing a common upper-level vocabulary may be seamlessly interwoven. Finally, we outline future work, including bacteria and fungus infectious disease reference ontologies currently under development, then cite uses of VIDO and CIDO in host-pathogen data analytics, electronic health record annotation, and ontology conflict-resolution projects.

A comprehensive update on CIDO: the community-based coronavirus infectious disease ontology.

BACKGROUND: The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO) in early 2020. RESULTS: As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. CONCLUSION: CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications.

Effect of low dose acetylsalicylic acid and anticoagulant on clinical outcomes in COVID-19, analytical cross-sectional study.

Background and aims: The therapeutic strategy for the treatment of known sequelae of COVID-19 has shifted from reactive to preventative. In this study, we aim to evaluate the effects of acetylsalicylic acid (ASA), and anticoagulants on COVID-19 related morbidity and mortality. Methods: This record-based analytical cross-sectional study targeted 539 COVID-19 patients in a single United States medical center between March and December 2020. Through a random stratified sample, we recruited outpatient (n = 206) and inpatient (n = 333) cases from three management protocols, including standard care (SC) (n = 399), low-dose ASA only (ASA) (n = 112), and anticoagulation only (AC) (n = 28). Collected data included demographics, comorbidities, and clinical outcomes. The primary outcome measure was inpatient admission. Exploratory secondary outcome measures included length of stay, 30-day readmission rates, medical intensive care unit (MICU) admission, need for mechanical ventilation, the occurrence of acute respiratory distress syndrome (ARDS), bleeding events, clotting events, and mortality. The collected data were coded and analyzed using standard tests. Results: Age, mean number of comorbidities, and all individual comorbidities except for asthma, and malignancy were significantly lower in the SC compared to ASA and AC. After adjusting for age and comorbidity via binary logistic regression models, no statistical differences were found between groups for the studied outcomes. When compared to the SC group, ASA had lower 30-day readmission rates (odds ration [OR] 0.81 95% confidence interval [CI] 0.35-1.88, p = 0.63), MICU admission (OR 0.63 95% CI 0.34-1.17, p = 0.32), ARDS (OR 0.71 95% CI 0.33-1.52, p = 0.38), and death (OR 0.85 95% CI 0.36-1.99, p = 0.71). Conclusion: Low-dose ASA has a nonsignificant but potentially protective role in reducing the risk of COVID-19 related morbidity and mortality. Our data suggests a trend toward reduced 30-day readmission rates, ARDS, MICU admissions, need for mechanical ventilation, and mortality compared to the standard management protocol. Further randomized control trials are needed to establish causal effects.

A new framework for host-pathogen interaction research.

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed.

Acetylsalicylic Acid Compared with Enoxaparin for the Prevention of Thrombosis and Mechanical Ventilation in COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVE: Low-dose acetylsalicylic acid (ASA, aspirin) is a well-known and frequently studied drug for primary and secondary prevention of disease due to its anti-inflammatory and coagulopathic effects. COVID-19 complications are attributed to the role of thrombo-inflammation. Studies regarding the use of low-dose ASA in COVID-19 are limited. For this reason, we propose that the use of low-dose ASA may have protective effects in COVID-19-related thromboembolism and lung injury. This study was conducted to assess the efficacy of low-dose ASA compared with enoxaparin, an anticoagulant, for the prevention of thrombosis and mechanical ventilation. METHODS: We conducted a retrospective cohort study on COVID-19-confirmed hospitalized patients at the Mansoura University Quarantine Hospital, outpatients, and home-isolated patients from September to December 2020 in Mansoura governorate, Egypt. Binary logistic regression analysis was used to assess the effect of ASA compared with enoxaparin on thromboembolism, and mechanical ventilation needs. RESULTS: This study included 225 COVID-19 patients. Use of ASA-only (81-162 mg orally daily) was significantly associated with reduced thromboembolism (OR 0.163, p = 0.020), but both low-dose ASA and enoxaparin, and enoxaparin-only (0.5 mg/kg subcutaneously (SC) daily as prophylactic dose or 1 mg/kg SC every 12 hours as therapeutic dose) were more protective (odds ratio [OR] 0.010, OR 0.071, respectively, p < 0.001). Neither ASA-only nor enoxaparin-only were associated with a reduction in mechanical ventilation needs. Concomitant use of low-dose ASA and enoxaparin was associated with reduced mechanical ventilation (OR 0.032, 95% CI 0.004-0.226, p = 0.001). CONCLUSIONS: Low-dose ASA-only use may reduce the incidence of COVID-19-associated thromboembolism, but the reduction may be less than that of enoxaparin-only, and both ASA and enoxaparin. Concomitant use of ASA and enoxaparin demonstrates promising results with regard to the reduction of thrombotic events, and mechanical ventilation needs.

Rationales and uncertainties for aspirin use in COVID-19: a narrative review.

OBJECTIVES: To review the pathophysiology of COVID-19 disease, potential aspirin targets on this pathogenesis and the potential role of aspirin in patients with COVID-19. DESIGN: Narrative review. SETTING: The online databases PubMed, OVID Medline and Cochrane Library were searched using relevant headlines from 1 January 2016 to 1 January 2021. International guidelines from relevant societies, journals and forums were also assessed for relevance. PARTICIPANTS: Not applicable. RESULTS: A review of the selected literature revealed that clinical deterioration in COVID-19 is attributed to the interplay between endothelial dysfunction, coagulopathy and dysregulated inflammation. Aspirin has anti-inflammatory effects, antiplatelet aggregation, anticoagulant properties as well as pleiotropic effects on endothelial function. During the COVID-19 pandemic, low-dose aspirin is used effectively in secondary prevention of atherosclerotic cardiovascular disease, prevention of venous thromboembolism after total hip or knee replacement, prevention of pre-eclampsia and postdischarge treatment for multisystem inflammatory syndrome in children. Prehospital low-dose aspirin therapy may reduce the risk of intensive care unit admission and mechanical ventilation in hospitalised patients with COVID-19, whereas aspirin association with mortality is still debatable. CONCLUSION: The authors recommend a low-dose aspirin regimen for primary prevention of arterial thromboembolism in patients aged 40-70 years who are at high atherosclerotic cardiovascular disease risk, or an intermediate risk with a risk-enhancer and have a low risk of bleeding. Aspirin's protective roles in COVID-19 associated with acute lung injury, vascular thrombosis without previous cardiovascular disease and mortality need further randomised controlled trials to establish causal conclusions.

Multiple Thrombotic Events in a 67-Year-Old Man 2 Weeks After Testing Positive for SARS-CoV-2: A Case Report.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral pathogen responsible for coronavirus disease 2019 (COVID-19), a pandemic respiratory illness. While many patients experience mild to moderate symptoms, severely affected patients often progress to acute respiratory distress syndrome (ARDS). Specific to COVID-19, abnormal coagulability appears to be a principal instigator in the progression of disease severity and mortality. In this report we summarize a case of COVID-19 in which extreme thrombophilia led to patient demise. CASE REPORT A 67-year-old man in New York presented to the hospital 14 days after testing positive for SARS-CoV-2 at an outpatient site. His initial presenting symptoms included sore throat, headache, fever, and diarrhea. He was brought in by his wife after developing sudden onset confusion and dysarthria. The patient's clinical picture, which was unstable on presentation, further deteriorated to involve significant desaturations, generalized seizure activity, and cardiac arrest requiring resuscitation. Upon return to spontaneous circulation, the patient required intensive care unit admission, mechanical ventilation, and vasopressor increases. Comprehensive workup uncovered coagulopathy with multiple thrombotic events involving the brain and lungs as well as radiographic evidence of severe lung disease. In the face of an unfavorable clinical picture, the family opted for comfort care measures. CONCLUSIONS In this case report on a 67-year-old-man with COVID-19, we present an account of extreme hypercoagulability that led to multiple thrombotic events eventually resulting in the man's demise. Abnormal coagulation 14 days from positive testing raises the question of whether outpatients with COVID-19 should be screened for hypercoagulability and treated with prophylactic anticoagulation/antiplatelet agents.

A proposal for an alcohol purchase license.

Background: Recent advances in technology have allowed for innovative targeting of high-risk alcohol users.Objectives: We propose the implementation of an alcohol purchase license linked to a state agency managed database, or so-called Banned Drinker Register (BDR).Methods: Individuals who are unable to drink safely will be identified by a well-founded criterion and their ability to purchase alcohol proscribed. A state agency will be responsible for maintaining the BDR and compiling mandated reports from hospitals, courts, police and child protective agencies of alcohol-related dangerous behavior, adjudicating reports with the input of those involved in these events, and determining which individuals will not be allowed to purchase alcohol. Outlets of alcohol sales will then be required to assess customers for eligibility of alcohol purchase using an electronic card reader (as used for age verification). Individuals wanting to protect themselves from drinking may also self-request to be placed on the BDR.Results: Overall, the convenience/access for persons who injure themselves with alcohol and others with intoxicated behavior would be reduced. Opportunities for cost savings would come from a decrease in yearly incarcerations, a reduction in preventable traffic accidents and property damage requiring state municipal intervention, a decreased cost to offending individuals by preventing increased insurance rates, loss of jobs to incarceration and loss of potential future wages, and the possibility of preventing long term medical complications of chronic alcohol use and its toll on the health care system.Conclusions: Health benefits will include increased public safety and awareness about drinking consequences and reduced alcohol-related morbidity and mortality.