ABSTRACT
The development of SARS-CoV-2 vaccines during the COVID-19 pandemic has prompted the emergence of COVID-19 vaccine data. Timely access to COVID-19 vaccine information is crucial to researchers and public. To support more comprehensive annotation, integration, and analysis of COVID-19 vaccine infor-mation, we have developed Cov19VaxKB, a knowledge-focused COVID-19 vaccine database (http://www. violinet.org/cov19vaxkb/). Cov19VaxKB features comprehensive lists of COVID-19 vaccines, vaccine for-mulations, clinical trials, publications, news articles, and vaccine adverse event case reports. A web-based query interface enables comparison of product information and host responses among various vaccines. The knowledge base also includes a vaccine design tool for predicting vaccine targets and a statistical analysis tool that identifies enriched adverse events for FDA-authorized COVID-19 vaccines based on VAERS case report data. To support data exchange, Cov19VaxKB is synchronized with Vaccine Ontology and the Vaccine Investigation and Online Information Network (VIOLIN) database. The data integration and analytical features of Cov19VaxKB can facilitate vaccine research and development while also serving as a useful reference for the public. (c) 2022 University of Michigan. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
ABSTRACT
Introduction Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is particularly serious in patients with multiple myeloma (MM), with estimated mortality of over 30% in several studies. In the general population, SARS-CoV-2 vaccination has been demonstrated to be an effective approach to preventing infection. However, patients with MM were not included in vaccination trials. Recent studies suggest that patients with compromised immune systems exhibit reduced antibody response to SARS-CoV-2 vaccination, and MM patients are often immunocompromised both due to MM itself and due to MM treatment. Thus, the objective of this retrospective cohort study in the national Veterans Affairs (VA) healthcare system was to evaluate the real-world effectiveness of SARS-CoV-2 vaccination to prevent COVID-19 infection in MM patients during the 140-day period following initial vaccine availability. Methods This is a multicenter study of SARS-CoV-2 infection among vaccinated and unvaccinated patients at VA hospitals nationwide during the period from 12/15/2020 to 5/4/2021. We identified a cohort of MM patients who were alive and without prior SARS-CoV-2 infection on their date of vaccination or inclusion as a control. For added comparison with a less immunocompromised population, we also identified a cohort of cancer survivors, defined as patients with any solid or hematologic malignancy who had been treated with systemic cancerdirected therapy subsequent to 8/15/2010, but had not been treated with such therapy in the 6 months prior to vaccination or inclusion as a control, and were alive and without prior SARS-CoV-2 infection on that date. Vaccinated patients were exactly matched 1:1 to unvaccinated controls on race, VA facility, rurality of home address, cancer type, and treatment timing and modality with minimum distance matching on age. The primary exposure was receipt of a SARS-CoV-2 vaccine. The primary outcome was laboratory-confirmed SARS-CoV-2 infection. Vaccination effectiveness was defined as 1 minus the risk ratio of SARS-CoV-2 infection for vaccinated individuals compared to unvaccinated controls. Results 6,891 MM patients met eligibility criteria and 4,367 were vaccinated during the study period. Of those, 1,606 vaccinated MM patients were matched 1:1 to 1,606 unvaccinated or not yet vaccinated controls. In addition, for comparison, 2,476 vaccinated cancer survivors were matched 1:1 to 2,476 unvaccinated or not yet vaccinated controls. Median follow-up was 44 days among MM patients and 46 days among cancer survivors. Vaccine effectiveness in the matched cohort of MM patients was 22.2% (95% CI, -133 to 82.7%) starting 14 days after the second dose. In contrast, effectiveness was 82.3% (95% CI 16.4 to 100%) starting 14 days after the second dose in the matched cohort of cancer survivors. Among vaccinated MM patients in the matched cohort, 14 (8.7 per 1000 patients) were infected with SARS-CoV-2 subsequent to vaccination. Among vaccinated cancer survivors in the matched cohort, 10 (4.0 per 1000 patients) were infected subsequent to vaccination. Conclusion Vaccination is an effective strategy for preventing SARS-CoV-2. However, effectiveness may be reduced in patients with MM, likely due to a co-existing immunosuppression both due to the disease process as well as associated therapy. Future studies are needed to evaluate the relationship between MM disease states, types of therapy used and treatment timing that may impact vaccine effectiveness, and to also determine if MM patients would benefit from post-vaccination serologies or a booster vaccination.
ABSTRACT
Ontologies have emerged to become critical to support data and knowledge representation, standardization, integration, and analysis. The SARS-CoV-2 pandemic led to the rapid proliferation of COVID-19 data, as well as the development of many COVID-19 ontologies. In the interest of supporting data interoperability, we initiated a community-based effort to harmonize COVID-19 ontologies. Our effort involves the collaborative discussion among developers of seven COVID-19 related ontologies, and the merging of four ontologies. This effort demonstrates the feasibility of harmonizing these ontologies in an interoperable framework to support integrative representation and analysis of COVID-19 related data and knowledge. © 2021 Copyright for this paper by its authors.
ABSTRACT
Purpose Guidance for managing orthotopic heart transplant (OHT) recipients with COVID-19 infection is limited. There have been 80 published cases of OHT recipients with COVID-19 infection to date, and they show a higher incidence of infection and greater mortality (26-41%) than that observed in the general population. Remdesivir, an inhibitor of viral RNA-dependent RNA polymerase, decreases median recovery time from infection in the general population, but was not used in any OHT patients. We sought to determine the effectiveness of remdesivir to treat COVID-19 in OHT recipients. Methods Out of 400 OHT patients followed at UCSD, 1.8% (n=7) have tested positive for COVID-19. Four of these patients were treated with remdesivir. Three patients with milder symptoms did not require treatment. Results OHT recipients with COVID-19 infection were a median 55 years of age (range 28-62 years), 71% (5/7) were male, and they were a median of 3 years post-transplant (range 2-5 years). All patients were taking tacrolimus, 85% (6/7) were also taking mycophenolate mofetil (MMF) or 14% (1/7) were taking mammalian target of rapamycin (mTOR) inhibitors. All patients had positive nasopharyngeal COVID-19 PCR and were admitted for observation. MMF and mTOR inhibitors were held on admission while tacrolimus was continued. Four patients (57%) developed hypoxia requiring supplemental oxygen or had pulmonary infiltrates on chest x ray and were treated with remdesivir. Patients received an intravenous (IV) infusion of 200 mg loading dose followed by 100 mg IV daily over 4 days (total 5 doses). Two patients were also treated with IV antibiotics for bacterial pneumonia (n=1) or urinary tract infection (n=1). Three of the four patients treated with remdesivir had complete resolution of fevers, hypoxia and symptoms after a 5-day course. The fourth patient had continued hypoxia requiring supplemental O2 therapy and received an additional 5 days of remdesivir 100 mg IV daily (10-day total course) with subsequent resolution of symptoms. No patients were intubated or admitted to intensive care and all 7 patients survived to hospital discharge and had negative COVID-19 PCR at outpatient follow up. No other COVID-19 directed therapies were used. Conclusion Compared to 80 patients in prior published cases, our experience suggests that prompt administration of remdesivir improves outcomes in OHT patients with COVID-19 infection.
ABSTRACT
Driven by the use cases of PubChemRDF and SCAIView, we have developed a first community-based clinical trial ontology (CTO) by following the OBO Foundry principles. CTO uses the Basic Formal Ontology (BFO) as the top level ontology and reuses many terms from existing ontologies. CTO has also defined many clinical trial-specific terms. The general CTO design pattern is based on the PICO framework together with two applications. First, the PubChemRDF use case demonstrates how a drug Gleevec is linked to multiple clinical trials investigating Gleevec’s related chemical compounds. Second, the SCAIView text mining engine shows how the use of CTO terms in its search algorithm can identify publications referring to COVID-19-related clinical trials. Future opportunities and challenges are discussed. Copyright © 2020 for this paper by its authors.
ABSTRACT
Current COVID-19 pandemic and previous SARS/MERS outbreaks have caused a series of major crises to global public health. We must integrate the large and exponentially growing amount of heterogeneous coronavirus data to better understand coronaviruses and associated disease mechanisms, in the interest of developing effective and safe vaccines and drugs. Ontologies have emerged to play an important role in standard knowledge and data representation, integration, sharing, and analysis. We have initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO). As an Open Biomedical Ontology (OBO) library ontology, CIDO is an open source and interoperable with other existing OBO ontologies. In this article, the general architecture and the design patterns of the CIDO are introduced, CIDO representation of coronaviruses, phenotypes, anti-coronavirus drugs and medical devices (e.g. ventilators) are illustrated, and an application of CIDO implemented to identify repurposable drug candidates for effective and safe COVID-19 treatment is presented. Copyright © 2020 for this paper by its authors.