The COVID-19 virus and its associated pandemic have highlighted the urgent need for a national infrastructure to rapidly identify and respond to emerging pathogens. The importance of understanding viral population dynamics through genetic sequencing has become apparent over time, particularly as the vaccine responses, clinical implications, and therapeutic effectiveness of treatments have varied substantially with COVID-19 variants.1,2
As the largest integrated health care system in the US, the US Department of Veterans Affairs (VA) is uniquely situated to help with pandemic detection and response. This article highlights 2 VA programs dedicated to COVID-19 sequencing at the forefront of pandemic response and research: VA Sequencing for Research Clinical and Epidemiology (SeqFORCE) and VA Sequencing Collaborations United for Research and Epidemiology (SeqCURE) (Table).
VA SeqFORCE
VA SeqFORCE was established March 2021 to facilitate clinical surveillance of COVID-19 variants in the US veteran population and in VA employees. VA SeqFORCE consists of 9 Clinical Laboratory Improvement Amendment (CLIA)–certified laboratories in VA medical centers, including the VA Public Health Reference Laboratory in Palo Alto, California, and 8 Veterans Health Administration (VHA) clinical laboratories (Los Angeles, California; Boise, Idaho; Iowa City, Iowa; Bronx, New York; West Haven, Connecticut; Indianapolis, Indiana; Denver, Colorado; and Orlando, Florida).3 Specimen standards (eg, real-time polymerase chain reaction [RT-PCR] cycle threshold [Ct] ≤ 30, minimum volume, etc) and clinical criteria (eg, COVID-19–related deaths, COVID-19 vaccine escape, etc) for submitting samples to VA SeqFORCE laboratories were established, and logistics for sample sequencing was centralized, including providing centralized instructions for sample preparation and to which VA SeqFORCE laboratory samples should be sent.
These laboratories sequenced samples from patients and employees with COVID-19 to understand patterns of variant evolution, vaccine, antiviral and monoclonal antibody response, health care–associated outbreaks, and COVID-19 transmission. As clinically relevant findings, such as monoclonal antibody treatment failure, emerged with novel viral variants, VA SeqFORCE was well positioned to rapidly detect the emergent variants and inform better clinical care of patients with COVID-19. Other clinical indications identified for sequencing within VA SeqFORCE included outbreak investigation, re-infection with COVID-19 > 90 days but < 6 months after a prior infection, extended hospitalization of > 21 days, death due to COVID-19, infection with a history of recent nondomestic travel, rebound of symptoms after improvement on oral antiviral therapy, and epidemiologic surveillance.
VA SeqFORCE laboratories use a variety of sequencing platforms, although a federated system was developed that electronically linked all laboratories using a software system (PraediGene, Bitscopic) for sample management, COVID-19 variant analytics, and automated result reporting of clade and lineage into the Veterans Health Information Systems and Technology Architecture (VistA) Computerized Patient Record System. In addition, generated nucleic acid sequence alignment through FASTA consensus sequence files have been archived for secondary research analyses. By archiving the consensus sequences, retrospective studies within the VA have the added benefit of being able to clinically annotate investigations into COVID-19 variant patterns. As of August 2023, 43,003 samples containing COVID-19 have been sequenced, and FASTA file and metadata upload are ongoing to the Global Initiative on Sharing Avian Influenza Data, which houses > 15 million COVID-19 files from global submissions.
VA SeqFORCE’s clinical sequencing efforts have created opportunities for multicenter collaboration in variant surveillance. In work from December 2021, investigators from the James J. Peters VA Medical Center in Bronx, New York, collaborated with the VHA Pathology and Laboratory Medicine Services and Public Health national program offices in Washington, DC, to develop an RT-PCR assay to rapidly differentiate Omicron from Delta variants.4 Samples from VA hospitals across the nation were used in this study.
Lessons from VA SeqFORCE have also been cited as inspiration to address COVID-19 clinical problems, including outbreak investigations in hospital settings and beyond. Researchers at the Iowa City VA Health Care System, for example, proposed a novel probabilistic quantitative method for determining genetic-relatedness among COVID-19 viral strains in an outbreak setting.5 They extended the scope of work to develop COVID-19 outbreak screening tools combining publicly available algorithms with targeted sequencing data to identify outbreaks as they arise.6 We expect VA SeqFORCE, in conjunction with its complement VA SeqCURE, will continue to further pandemic surveillance and response.