Responding to Emergent Societal Issues: COVID Serology Research

DCCPS has much to offer in responding to emerging public health issues, including those issues that extend beyond our key mission of reducing the burden of cancer. The COVID-19 pandemic has provided a powerful example of how the division is able to rapidly scale up research by leveraging funding opportunities, partnerships, data infrastructure and linkages, and analytical expertise. While cancer control research is the division’s priority and focus, DCCPS is contributing critical expertise in serological sciences, data gathering, and analysis to help address key research questions related to the global pandemic.

Studying SARS-CoV-2 Antibodies and Virus Reinfection

In 2020, DCCPS launched a study to better understand whether, and to what degree, detectable antibodies against SARS-CoV-2 protect people from reinfection with the virus. Working with HealthVerity and Aetion, a research team led by DCCPS staff aggregated and analyzed patient information collected from multiple sources, including five commercial labs, EHRs, and private insurers.

The study, published on February 24, 2021, in JAMA Internal Medicine, found that people who have had evidence of a prior infection with SARS-CoV-2 appear to be well protected against reinfection, at least for a few months. This finding has important public health implications, including decisions about returning to physical workplaces, school attendance, the prioritization of vaccine distribution, and other activities.

To continue to comprehensively address this important research question, NCI is supporting clinical “seroprotection” studies that monitor infection rates in large populations of people whose antibody status is known. NCI is also sponsoring ongoing studies using real-world data to assess the longer-term association between antibody positivity and subsequent infection rates.

NCI Serological Sciences Network (SeroNet)

DCCPS has played a key role as part of the NCI-led Serological Sciences Network (SeroNet), a coordinated effort to study the immune response to COVID-19. The network aims to combat the pandemic by improving the ability to test for infection, especially among diverse populations, and speed the development of treatments and vaccines.

Serologic testing for SARS-CoV-2 antibodies can identify persons who have been exposed and infected with SARS-CoV-2 at any time and might be a correlate of protective immunity. Serological studies at the population level will improve our understanding of the severity of the pandemic, the strength and duration of immunity, how infection varies across demographic groups, and the robustness of the immune response after infection or vaccination.

Serologic testing for the presence of SARS-CoV-2 antibodies is also a critical tool for understanding the epidemiology of COVID-19 and designing control strategies for the pandemic. NCI-supported studies in DCCPS’s grant portfolio related to these issues include the following:

• A series of linked studies embedded in a large, integrated health system (Kaiser Permanente Northern California) with a significant number of COVID-19 patients, high SARS-CoV-2 testing capacity, and linked rich demographic, behavioral, and clinical data will assess SARS-CoV-2 seroprevalence, sero-incidence, risk of seroconversion, and longevity of antibody response.
• Investigators at The Ohio State University will use serological and molecular tests to study first responders and their household contacts to understand transmission in both asymptomatic and symptomatic individuals; immune, host, and viral determinants of disease outcomes; factors associated with immune protection; and best practices for communication of test results and COVID-19 information.
• The Harvard SeroSciences Center will develop new methods for serological data analysis, design studies to test and refine these methods, and create novel modeling tools to monitor population immunity to COVID-19 and other infections.

Racial/ethnic minorities bear a disproportionate burden of the incidence, morbidity, and mortality from SARS-CoV-2 infection. In addition to multiple factors that lead to disproportionate rates of infection—such as structural racism and discrimination, higher rates of preexisting health conditions, and delayed or limited access to healthcare — differences in immune response to SARS-CoV-2 may also play a part in this disparity. NCI-supported studies in DCCPS’s grant portfolio related to COVID-19 health disparities include the following:

• Investigators at the University of Arkansas for Medical Sciences established a population-based, observational prospective cohort study with a racially, ethnically, and geographically diverse, representative sample of all noninstitutionalized adults residing in Arkansas tested by real-time, reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19 between November 2020 and April 2021. The cohort will be followed up to 48 months post-testing to determine serological responses to SARS-CoV-2 infection, the durability of response, and multiple factors associated with immune response by race and ethnicity.
• A study led by Michigan State University will develop and compare effects of a general-versus-culturally targeted video about antibody testing on African American and White Flint residents’ antibody testing attitudes and uptake. Additionally, the investigators will measure and identify multi-analyte inflammatory biomarker profiles among Flint Registry enrollees who complete salivary antibody testing and compare inflammatory biomarker profiles by race and antibody status.

Lessons learned from SeroNet research have had immediate public health implications and may prove valuable to public health beyond the current pandemic.