Creating Infrastructure to Study the Immune Response to SARS-CoV-2 in Wisconsin

At a Glance

This project sought to address problems in COVID-19 preparedness to reduce morbidity and mortality and to achieve the highest level of health for all people of Wisconsin. To do this, the research team created a biorepository to support research at the UW and beyond. They also evaluated the persistence of anti-SARS-CoV-2 antibodies.

The resulting biorepository contains extensive clinical data, serum, plasma, and immune cells collected over the course of a year from 120 subjects who recovered from COVID-19. In addition to supporting the research of multiple scientists at UW and nationally, the biorepository allowed the research team to demonstrate the presence of antibodies against the SARS-CoV-2 membrane protein in the human body for at least one year, and showed that antibodies that bind to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein are a long-lasting, sensitive, and specific marker of both past infection and vaccination. Thus, the researchers determined that a combination of these antibodies can accurately differentiate between distant COVID-19 infection, vaccination, and naïve states to advance public health, individual healthcare, and research goals.

The Challenge

When this project began, it was unknown how long antibodies against SARS-CoV-2 would last and there were no tools to study this question. In order to effectively plan strategies to protect communities during the COVID-19 pandemic and in the long term, there needed to be better understanding of protective immunity.

Project Goals

The goal of this project was to establish a biorepository to acquire and store COVID-19 convalescent blood products from individuals who had recovered from COVID-19. Additionally, the team aimed to determine if anti-SARS-CoV-2 antibodies persisted in those who recovered.

Results

This project successfully established the COVID-19 Convalescent Biorepository in collaboration with the University of Wisconsin’s Carbone Cancer Institute’s Translational Science Biocore (TSB) Biobank. The new biorepository contains extensive clinical data, serum, plasma, and peripheral blood mononuclear cells collected over the course of a year for 120 subjects who recovered from COVID-19.

The research team fostered additional successful collaborations that contributed to the important knowledge gained from this project. For example, very early in the pandemic, they partnered with Adrian McDermott, M.Sc, PhD, National Institute of Allergy and Infectious Disease, Vaccine Immunology Program, Yoshihiro Kawaoka, PhD, UW–Madison School of Medicine and Public Health, Department of Pathobiological Sciences, and their teams, to detect anti-SARS-CoV-2 antibodies in 98 percent of subjects recovering from COVID-19 five weeks after symptoms subsided. To detect this, the team used the National Institutes of Health (NIH) Vaccine Research Center’s newly developed antibody detection platforms and Dr. Kawaoka’s neutralizing antibody assays.
In collaboration with Ajay Sethi, PhD, MHS, UW–Madison School of Medicine and Public Health, Population Health Sciences, the research team found that increased anti-SARS-CoV-2 antibody levels correlated with greater disease severity, older age, male sex, higher body mass index, and higher Charlson Comorbidity Index score. They also reported that COVID-19 symptoms – most consistently fever, body aches, and low appetite – correlated with higher anti-SARS-CoV-2 antibody levels.

Researchers also collaborated with Irene Ong, PhD, UW–Madison School of Medicine and Public Health, Department of Obstetrics and Gynecology, and David O’Connor, PhD, UW–Madison School of Medicine and Public Health, Department of Pathology and Laboratory Medicine, to identify new parts of SARS-Cov-2 that are recognized by antibodies in people who recovered from COVID-19. The research team then demonstrated that antibodies that bind to the SARS-CoV-2 membrane protein had strong sensitivity (88 percent) and specificity (95 percent) for past COVID-19 infection, and persist at least one year (94 percent seropositive). They also demonstrated that antibodies that bind to the receptor binding domain (RBD) fragment of the SARS-CoV-2 spike protein are a long-lasting, sensitive, and specific marker of both past infection and vaccination. Thus, the researchers found that a combination of anti-membrane and anti-RBD antibodies can accurately differentiate between distant COVID-19 infection, vaccination, and naïve states to advance public health, individual healthcare, and research goals.

The results of the project have led to manuscripts that have been accepted for publication, patent applications, and preprints.

Looking to the Future

The COVID-19 Convalescent Biorepository is a sustainable resource for UW researchers to generate important findings related to SARS-CoV-2 infection and to apply for future funding. The researchers used samples collected in this study to generate preliminary data for grant applications currently being written.

Lasting Impact

The biorepository will serve as the foundation for multiple high impact UW studies as they compete for national funding. At least six other researchers have already used samples collected in this study, which will have innumerable short, medium, and long-term benefits for the health of Wisconsinites.