Leveraging the Million Veteran Program Infrastructure and Data for a Rapid Research Response to COVID-19

COVID-19 Research Partnerships

In 2016, the VA and DOE formed an interagency partnership known as Computational Health Analytics for Medical Precision to Improve Outcomes Now (CHAMPION) to demonstrate the power of combining the VA EHR system, MVP genetic data, and clinical research expertise with DOE high-performance computing infrastructure and artificial intelligence expertise. The VA EHR captures longitudinal care information on veterans with records that go back decades. Furthermore, the VA covers the costs of medications and provides a variety of services through the Veterans Benefits Administration. As a result, VA data include medications used by patients before, during, and after COVID-19. Similarly, the VA has comprehensive vital records, whereas other large health systems do not capture events such as death after patients leave the hospital.

The DOE Oak Ridge National Laboratory (ORNL) in Tennessee securely maintains this rich database for the VA. The ORNL Summit supercomputer can complete trillions of calculations per second to provide critical and timely analyses, applying the most advanced and powerful artificial intelligence methods, which would not be possible in more conventional research settings. CHAMPION taught the VA and DOE how to bring their disparate research cultures together for innovative collaborative investigation. Moreover, this collaboration produced a cadre of VA and DOE scientists familiar with VA patient data and experienced in conducting joint research successfully and integrating omics data with clinical data for a better mechanistic understanding. Because of this preexisting collaboration between the VA and DOE, interagency teams were prepared at the start of the COVID-19 pandemic.^10-15

During the pandemic, the FDA and VA conducted research together. One joint study found that the bradykinin storm is likely to play a role in many COVID-19 symptoms. Using VA data, researchers compared COVID-19 testing patterns, positive test results, and 30-day mortality rates by race and ethnicity among VA patients.^10,11 These findings demonstrated the higher burden COVID-19 placed on Black and Hispanic communities, not fully explained by underlying health conditions, access to medical care, or geographic locale.¹¹

Other recently completed studies have developed and validated short-term mortality indices in individuals with COVID-19 based on their preexisting conditions, assessed the generalizability of VA COVID-19 experiences to the US population, and evaluated the effectiveness of hydroxychloroquine with and without azithromycin in VA patients with COVID-19.^12,15 A recent study demonstrated the benefit of prophylactic anticoagulation at initial hospitalization.¹⁴

The VA also provided the FDA with daily reports on aggregate VA COVID-19 cases and their distribution across the VA system, demographics of VA patients with COVID-19, and analyses of predictive models for positive test results and death. The VA regularly sent the FDA aggregated data showing patterns of medication use and retrospective analyses of the effectiveness of certain medications (including remdesivir and some antithrombotic agents). The FDA used these data along with other data to understand the scope of the pandemic and to predict drug shortages or needs for additional medical equipment, including ventilators. This information was critical at the start of the pandemic.

Limitations

For the most part, MVP infrastructure and partnerships were efficiently leveraged to significantly advance our understanding of the biological basis of COVID-19 and to develop treatments and vaccines. However, there were a few limitations that may have slowed timely and optimal outcomes. An issue not limited to the MVP or VA was the continual evolution of the pandemic and its response. This included evolving definitions of disease, symptomatology, testing, vaccines, and public health recommendations. Keeping pace with the emerging knowledge from these domains was a struggle for the entire scientific community. A more discrete limitation was the number of participants in the MVP with positive COVID-19 test results and positive symptoms; however, this was mitigated by partnering with other groups like the COVID-19 Host Genetics Initiative to increase study participant numbers. Finally, there were logistical and regulatory challenges associated with coordination of national clinical trial recruitment across a VA system with > 100 discrete hospitals.

Conclusions

Having a centralized infrastructure for recruitment and enrollment, including a national research volunteer registry, information center, research staff, and coordinating centers, can allow for expedited enrollment in vaccine and treatment trials in the face of future public health emergencies. VA assets, including its rich EHR and MVP, the world’s largest genomic cohort, have contributed to improving our understanding and management of COVID-19. MVP’s ready-to-respond research infrastructure embedded within the country’s largest national health care system allows for both the facilitation of the research work and applications of the research findings into practice. Findings from the MVP COVID-19 working groups have yielded compelling results, particularly around genetic variants among various racial and ethnic groups. Looking ahead, the VA and DOE are launching a new joint project on long COVID that will include developing a gold-standard definition for long COVID. The ORD has established a Partnered Research Program to facilitate collaborations with industry to speed up clinical trials, and the MVP will continue to contribute toward expanding scientific knowledge to improve the management of COVID-19.