CTSC resources have greatly benefitted the ability of many groups to inform policy and medical practice during the COVID pandemic. One example is the highly collaborative interdisciplinary team of Rong Xu, PhD, Director of the Center for Artificial Intelligence and Drug Discovery, David Kaelber, MD, MPH, lead of the CTSC Informatics module and Chief Medical Information Officer in the MetroHealth System, Pamela Davis, MD, PhD, of the Center for Community Health Integration and a CTSC associate PI, Nathan Berger, MD, Professor of Medicine and member of Case Comprehensive Cancer Center, and other collaborators who join the team as their special expertise is required.
Among their discoveries are:
- The observation that the incidence of COVID-19 infection in children sharply increased as the Omicron variant became more widespread (eight times higher than the rate when the Delta variant was predominant), but the severity of disease was substantially less as measured by hospitalization or ICU utilization. Incidence increased in older age groups, too, but to a lesser extent.
- Patients with dementia, cancer, substance abuse disorders, and those with liver diseases have increased risk for contracting severe COVID-19 compared to patients in a control group matched for demographics and other medical conditions reported to affect the severity of COVID.
- People who received the Moderna vaccine had fewer breakthrough infections than those who received the Pfizer vaccine in groups matched for demographics and other known COVID-19 risk factors.
- Breakthrough infection was more common in vaccinated individuals with substance abuse disorders, but this was accounted for by other medical conditions such as hypertension or cardiovascular disease (with the exception of cannabis use disorder, which conferred independent excess risk for breakthrough infection).
- Breakthrough infection was more common in vaccinated individuals with dementia than in matched individuals who were not diagnosed with dementia.
- Breakthrough infection was more common in individuals with cancer, especially those with hematologic malignancies.
- Rebound following Paxlovid treatment is not more common than it is following treatment with other antivirals.
- Children who were infected with SARS-CoV2 had a twofold excess risk of a new diagnosis of type 1 diabetes compared to children who had a well child visit or a visit for other non-COVID respiratory infections in the six months following infection.
- For at least a year following infection with SARS-CoV2, there is a twofold elevation of risk of new diagnosis of Alzheimer’s disease compared to matched individuals who were not diagnosed with SARS-CoV2 infection.
- Combining observations from several papers, there are significant racial and ethnic disparities in initial infection with SARS-CoV2 in unvaccinated individuals, but the racial inequities are no longer significant for breakthrough infections after vaccination. However, age usually remains a significant risk factor in most analyses of COVID severity, with or without vaccination, drugs, or underlying conditions.
Studies in progress include examining long-term effects of COVID-19 (long COVID) and identifying potential therapeutic treatments for long COVID. Currently the team is analyzing hepatic dysfunction in children, neurodegenerative disorders, substance abuse disorders, and mental health disorders in children and adult COVID survivors. The findings may help public health decision-makers and the general public prioritize certain patient populations for vaccines and anti-viral treatment, guide vaccine selection for people who are most vulnerable, and increase monitoring of vulnerable populations for longer term consequences. The group is also investigating the impact of drugs on long-term COVID complications, and the possible protective effects of drugs taken for other conditions on the severity of COVID and the potential for long term COVID symptoms. Applying informatics tools to a very large, updated data set has been an important contribution to decision making during the rapidly changing COVID-19 pandemic. As evidence of their impact, these COVID papers have been published in >15 high-impact journals, cited more than 1,400 times (as of September, 2022), featured in thousands of news articles around the world, and included in CDC guidelines for identifying vulnerable populations for COVID-19 susceptibility and outcomes.
An important tool for this work has been a large database of more than 100 million de-identified electronic health records, updated daily, so it provides, in near-real time, population-based data on COVID-19. Although these studies are retrospective and observational, they can be conducted quickly and help guide future prospective, interventional studies, as well as informing decisions by policy makers that must be made quickly before prospective studies can be completed.
Another important aspect of these studies for the CTSC, considering its major goal to develop the clinical research work force, is the extensive participation of students in these studies. Lindsey Wang, a high school student who enrolled in Dr. Berger’s summer research program from the Case Comprehensive Cancer Center (Case CCC Youth Enjoy Science (YES) grant R25 CA221718), has produced an extraordinary output of papers on these topics and may be attracted to continue in biomedical and informatics research. Over the last year, four medical students, Maria Gorenflo, Ellen Kendall, Veronica Olaker, and Christina Wang, have participated in various aspects of these studies. They have become highly collaborative with each other and have submitted several papers together that are now in review, in addition to the observations on type 1 diabetes published recently in JAMA Network Open. Two new students have just joined us. Besides working on topics of interest to the professors, they have initiated studies on their own and have become facile with the embedded analytics programs in the database. These students are gaining understanding of the power and the limitations of electronic health record data, and of the value of collaborative work, both clearly important in clinical research. Their enthusiasm and growing understanding is invaluable in driving future studies.
To read the study, entitled “Pfizer to Test Second Paxlovid Course in Patients With Covid Rebound”, please click here.
Additional CWRU/COVID-19 news:
- COVID-19 Vaccines
Case Western Reserve University
CTSA Program In Action Goals
Goal 2: Engage Patients and Communities in Every Phase of the Translational Process
Goal 4: Innovate Processes to Increase the Quality and Efficiency of Translational Research, Particularly of Multisite Trials