image: Dr. Shikhar Mehrotra's team analyzed more than 60,000 blood samples as part of their large-scale COVID-19 antibody study. view more
Credit: MUSC Hollings Cancer Center
MUSC Hollings Cancer Center researchers added to the understanding of the protective immune response against the SARS-CoV-2 virus in a study published in April in iScience. The team found that approximately 3% of the population is asymptomatic, which means that their bodies can get rid of the virus without developing signs of illness.
The researchers screened more than 60,000 blood samples from symptomless individuals in the Southeastern U.S., including Georgia, South Carolina and North Carolina, for the IgG antibody to the viral spike protein.
What began as a highly collaborative statewide effort to detect SARS-CoV-2 accurately, when tests were lacking, has led to discoveries. Last year, Shikhar Mehrotra, Ph.D., professor, and scientific director of the FACT-accredited Clean Cell Therapy Unit at MUSC, led the task of developing a method to detect COVID-19 infections rapidly in patients.
The research team developed an orthogonal ELISA-based serological assay, which allows for large-scale antibody testing. While commercial antibody tests are now more readily available, the work has excellent strength in findings because of the exceptionally large sample size, said Mehrotra. Studies such as this shed light on the current unknowns, such as the longevity of the antibodies, their ability to protect from repeat infections and the protective concentration (titer) of neutralizing antibodies.
"As cancer researchers who focus on understanding the role of the immune system in cancer, we are well-positioned to tackle the difficult immunity questions raised by COVID-19. This work was a concerted effort with the highly skilled scientists in the Clean Cell Facility who processed this large sample population," said Mehrotra.
Disease-specific antibody research is necessary to understand protective immunity and understand more fully the prevalence of infection and immune responses to both the virus and vaccines. The team found that high levels of anti-S IgG, the antibody that detects the spike protein, and anti-RBD IgG, the antibody that detects the receptor-binding domain of the spike protein, strongly correlated with neutralizing activity, meaning they defend the person from the virus. Antibodies from 94 hospitalized COVID-19 patients were also assessed: the data showed that compared to asymptomatic individuals with high anti-S IgG, sick patients had decreased antibody responses and reduced neutralizing activity.
The data showed that younger (30 years old and younger) versus older individuals had the highest antibody responses. Also, the findings matched other reports indicating that COVID-19 is disproportionately high in African Americans in Southeastern states.
In the future, this tool can be used to monitor antibody levels upon vaccination or as a screening tool for therapeutic convalescent plasma. Since analyzing neutralizing antibodies in all patients and asymptomatic individuals is challenging, the results indicate that IgG anti-S or RBD can act as a surrogate in determining neutralizing activity in individuals tested for SARS-CoV-2 infection or vaccine response.
More studies are needed to understand the differences between neutralizing antibodies in asymptomatic and hospitalized individuals. Follow-up studies can be done with this extensive data set; for example, the biomarkers between asymptomatic and symptomatic individuals can be compared.
The increase in cross-disciplinary research reveals how novel strategies can accelerate research across medical subdisciplines. The development of mRNA-based COVID vaccines is anticipated to boost cancer research developments. For two decades, scientists have been trying to use RNA as a therapeutic but with little success, since RNA naturally degrades quickly. Now, with the COVID vaccines, it is apparent that stabilizing techniques are feasible and can be translated to other applications, such as cancer vaccines targeting markers on cancer cells or epitopes.
Identifying disease prevalence as a whole helps public health leaders to target interventions and prioritize resources. "Research across the biomedical research spectrum over the last year has demonstrated how public health can be accelerated by collaboration from all sectors, including academic, pharmaceutical and regulatory agencies," said Mehrotra.
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Funding support from the MUSC President's Office for COVID-19 research, South Carolina Clinical & Translational Research Award and in part by NIH R01CA138930 and R01CA250458.
About MUSC
Founded in 1824 in Charleston, MUSC is the oldest medical school in the South as well as the state's only integrated academic health sciences center with a unique charge to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and nearly 800 residents in six colleges: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. The state's leader in obtaining biomedical research funds, in fiscal year 2019, MUSC set a new high, bringing in more than $284 million. For information on academic programs, visit musc.edu.
As the clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest quality patient care available while training generations of competent, compassionate health care providers to serve the people of South Carolina and beyond. Comprising some 1,600 beds, more than 100 outreach sites, the MUSC College of Medicine, the physicians' practice plan and nearly 275 telehealth locations, MUSC Health owns and operates eight hospitals situated in Charleston, Chester, Florence, Lancaster and Marion counties. In 2020, for the sixth consecutive year, U.S. News & World Report named MUSC Health the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.
MUSC and its affiliates have collective annual budgets of $3.2 billion. The more than 17,000 MUSC team members include world-class faculty, physicians, specialty providers and scientists who deliver groundbreaking education, research, technology and patient care
About MUSC Hollings Cancer Center
MUSC Hollings Cancer Center is a National Cancer Institute-designated cancer center and the largest academic-based cancer research program in South Carolina. The cancer center comprises more than 100 faculty cancer scientists and 20 academic departments. It has an annual research funding portfolio of more than $44 million and a dedication to reducing the cancer burden in South Carolina. Hollings offers state-of-the-art diagnostic capabilities, therapies and surgical techniques within multidisciplinary clinics that include surgeons, medical oncologists, radiation therapists, radiologists, pathologists, psychologists and other specialists equipped for the full range of cancer care, including more than 200 clinical trials. For more information, visit hollingscancercenter.musc.edu.
Journal
iScience