Kaiser Permanente collaboration with public health surveillance can improve response to the next pandemic
Kaiser Permanente researchers — working with colleagues in public health and other research institutions — identified 78 new locations on the genome of SARS-CoV-2 that could relate to how the virus infects a person and impacts their health. The study was published in the journal PLOS One.
Previous genetic analysis of the virus that causes COVID-19 has focused on its spike gene, which codes for the protein that allows the virus to enter human cells. But other parts of the virus could also be relevant to how the virus affects human health, said study senior author Jacek Skarbinski, MD, a research scientist with the Kaiser Permanente Division of Research and infectious diseases physician with The Permanente Medical Group.
“The SARS-CoV-2 virus has been incredibly successful in not only infecting people initially — 8 billion or so times — it also infected a second and third and fourth wave,” Skarbinski said. “It must have remarkable ability for immune evasion. That’s why it’s important to look beyond the spike protein to other parts of the virus genome for clues about its behavior.”
This study was unique in combining genetic analysis with information about infected patients to determine their immunity status — whether they had been vaccinated against COVID-19 or had been infected before. The researchers thought they might find a connection between the newly identified mutations of the virus genome — known as SNPs — and patients’ immunity status. They did not find any such connections.
Skarbinski said that is not surprising in this type of study, which is meant to provide a detailed understanding of the complete virus genome. Discovering a new way the virus evades the human immune response, other than through mutations in the spike protein, would have been extraordinary, he said.
But the analysis provides both detailed information for continued study of SARS-CoV-2 and offers a blueprint for how a health system can contribute vital information about an infectious agent’s behavior in a future pandemic involving some other pathogen.
Searching unexplored regions
The study looked at data collected on 15,566 SARS-CoV-2 infections at Kaiser Permanente Northern California (KPNC) in 2022, during the period when the Omicron variant was dominant.
KPNC collaborates with the California Department of Public Health, contributing SARS-CoV-2 positive samples to the COVIDNet network for genomic sequencing. A number of universities, laboratories, and other research organizations also belong to COVIDNet, which was established to track genomics of the virus in real time to contribute current information for the development of vaccines.
KPNC was a contributor to the COVIDNet sequencing project, providing a large number of samples from a diverse group of patients, efficiently collected through its central laboratory, Skarbinski said. “We’ve been a small part of a unique public health partnership,” he said.
While the sequencing data has long been available, this analysis is unique in combining an individual patient’s virus DNA with their immunity status — whether they have been vaccinated or have had COVID-19 in the past. “Our work looks much deeper at all the molecular machinery that the virus uses,” Skarbinski said.
It is unusual to have this much information about a given pathogen’s genomics, he said. COVID-19 has been studied in greater detail than other infectious diseases because it had such widespread impact on human health and society. COVID-19 is also unusual in how quickly it evolves, compared with other pathogens, Skarbinski said.
Of the 15,566 individuals infected with Omicron included in the study, 12% were unvaccinated with no previous recorded infection, 2% were unvaccinated with a previous infection, 86% had completed a primary vaccination series, and 58% had at least one booster vaccination.
Each sample was sequenced and analyzed for significant mutations — changes in the genome over time beyond those identifying it as belonging to a subvariant, such as Omicron BA.1 or BA.2. “The mutations we identified were diverse, some only appearing in a single subvariant or time period, and others appearing everywhere,” explained lead author Joshua Nugent, PhD, a biostatistician with the Division of Research.
The analysis looked for any connection between the unique SNPs and patients’ varying immune status, but did not find a significant association, or signal.
“It would have been more exciting if we had found an association,” Nugent said. “But it is still valuable to carry out a study that combines the detailed genomic data about the virus and the patients’ immunity status. That study design can be used more in the future to learn more about how this and other viruses behave in the real world.”
“For every one big scientific discovery, we have 999 where we do the work and don’t find anything,” Skarbinski said. “But the process of carrying out the studies is very important. We were looking at unexplored regions of the SARS-CoV-2 virus, and didn’t know what we might find.”
The study was funded by the Rockefeller Foundation, the National Cancer Institute of the National Institutes of Health, the Physician Researcher Program of The Permanente Medical Group Delivery Science and Applied Research Program, the Packard Foundation, and the Sergey Brin Family Foundation. CDPH/COVIDNet genomic surveillance work was funded by Centers for Disease Control and Prevention, Epidemiology and Laboratory Capacity for Infectious Diseases.
Additional co-authors were Mariah S. Wood, MPH, Liyan Liu, Laura B. Amsden, MSW, MPH, and Crystal A. Hsiao, MPH, of the Division of Research; Teal Bullick, BS, Phacharee Arunleung, BS, Gautham Gautham, MPH, Shiffen Getabecha, MPH, Christina Morales, PhD, and Debra A. Wadford, PhD, of the California Department of Public Health Viral and Rickettsial Disease Laboratory; Jeffrey M. Schapiro, MD, of the Innovative Genomics Institute at the University of California Berkeley; and Stacia K. Wyman, PhD, of Kaiser Permanente Oakland Medical Center.
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About the Kaiser Permanente Division of Research
The Kaiser Permanente Division of Research conducts, publishes, and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. KPDOR seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 720-plus staff, including 73 research and staff scientists, are working on nearly 630 epidemiological and health services research projects. For more information, visit divisionofresearch.kp.org or follow us @KPDOR.
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