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COVID-19 Research Across the Division: DCEG Experts Address the Pandemic

, by Sharon A. Savage, M.D., and Jennifer K. Loukissas, M.P.P.

DCEG staff continue to apply their unique set of analytic skills and subject matter expertise to major epidemiological questions presented by the COVID-19 pandemic while maintaining focus on their primary mission to understand the causes of cancer. Below are summaries of recently completed investigations and ongoing projects.

Recently Completed Investigations

dACE2 is a new, shorter form of ACE2, the receptor SARS-CoV-2 uses to enter cells.

NCI researchers identified dACE2, a new, shorter form of ACE2, the receptor SARS-CoV-2 uses to enter cells. dACE2 is expressed in cells exposed to SARS-CoV-2 or interferon but isn't a receptor for the virus. (Created with BioRender.com)

Credit: National Cancer Institute

Novel Isoform of ACE2 Uncovered

An international team of researchers, led by Ludmila Prokunina-Olsson, Ph.D., chief of the Laboratory of Translational Genomics, identified a novel isoform of ACE2 (the cell receptor used by the SARS-CoV-2 virus to infect the body) which they designated deltaACE2 (dACE2). The paper was published in Nature Genetics, on October 19, 2020, and was summarized on the DCEG website.

Impact of Population Growth and Age Distribution on COVID-19 Mortality Estimates

Meredith Shiels, Ph.D., investigator in the Infections and Immunoepidemiology Branch (IIB), Amy Berrington, D.Phil., chief of the Radiation Epidemiology Branch (REB), and colleagues applied descriptive epidemiological approaches to better understand the patterns of death over part of 2020—those from COVID-19 and other causes. They concluded that accounting for recent population aging is critical, as the size of the U.S. population aged 65+ increased dramatically in the preceding five years. The article was published December 15, 2020, in Annals of Internal Medicine.  

Evaluating Risks and Benefits from Radiation for COVID-19 Management

Experts in the Radiation Epidemiology Branch (REB) have been carefully following the use of medical ionizing radiation within the context of the pandemic, for both monitoring and treatment. Choonsik Lee, Ph.D., head of the Dosimetry Unit, has written about the wide variation in the use of chest CT and radiation dose in a commentary published in November 2020 in Radiology.

Mark Little, D.Phil., senior investigator in REB, published a re-analysis of radiobiology data, which may cast a light on the risk-benefit of recent proposals to use low-dose radiotherapy to treat COVID-19-associated pneumonia, in September 2020 in the International Journal of Radiation Oncology, Biology & Physics.

Ongoing Research

Effects of the Pandemic on Physical Activity and Sedentary Behavior

The COVID-19 pandemic has brought innumerable changes. For many, the biggest shift has been staying home, with residual effects on daily physical activity and sedentary behaviors. Increased physical activity and decreased sedentary behaviors are associated with health benefits, including reduced risk of some cancers. To evaluate the effect of the pandemic on these patterns, Charles E. Matthews, Ph.D., senior investigator in the Metabolic Epidemiology Branch (MEB), and colleagues in the Division of Cancer Control and Population Sciences, will compare data collected from a nationwide survey of 2,500 adults in Fall 2019 (pre-pandemic) with those from Fall 2020, using the NCI-developed tool Activities Completed over Time in 24-hours (ACT24).

The follow-up survey was conducted among 3,800 adults in the AmeriSpeak® panel, a representative sample maintained by NORC at the University of Chicago. Specific studies will focus on the effect of the pandemic on time-use and estimated daily energy expenditure by evaluating changes to patterns at work, home, in leisure-time, sleep, and physical activity.

Volunteering on the Front Lines

Neelam Giri, M.D., M.B.B.S., staff clinician, and Michael Sargen, M.D., clinical fellow, both in CGB, continue to volunteer in the symptomatic testing of NIH staff. Dr. Giri was one of the first clinicians at the NIH to receive the first of two doses of the Moderna vaccine.

Neelam Giri receives a covid vaccine at the NIH clinical center.

Dr. Giri is vaccinated at the NIH Clinical Center.

Credit: NIH

Seroprevalence Studies Available through SeroHub

Neal D. Freedman, Ph.D., M.P.H., senior investigator in MEB, and colleagues launched the COVID-19 Seroprevalence Studies Hub (SeroHub) to compare COVID-19 seroprevalence studies across the country. This project was the result of a collaboration including epidemiologists, data scientists, data engineers, and other researchers at the NCI, the Centers for Disease Control and Prevention, and the National Institute of Allergy and Infectious Diseases (NIAID). Since its launch, the investigators have been adding studies to the resource and developing new visualization features that will better allow users to sort and visualize U.S. seroprevalence studies. 

COVNET and COVIDcode Accrual Accelerating 

The two studies of genetic contributions to severity of COVID-19 are well underway, both rapidly accruing participants. COVNET is a large genome-wide association study (GWAS) to identify common and rare germline variants associated with susceptibility to severe or fatal COVID-19 disease. At least 25 institutions are collaborating with DCEG on this effort, with a goal of including up to 40,000 de-identified samples. The COVIDcode study contributes to COVNET and is designed to elucidate the immunologic contributions to COVID-19 severity. 

COV2Base Study

Researchers in the Clinical Genetics Branch (CGB) are monitoring the effect of the pandemic on special populations. They have launched a collaboration with the National Heart, Lung, and Blood Institute to examine the effect of SARS-CoV2 infection on patients with rare diseases (e.g., Li-Fraumeni Syndrome, DICER1-syndrome, inherited bone marrow failure syndromes), quantifying frequency and severity and looking for conditions that may increase risk of severe outcomes. Additionally, they are working to identify genetic, tissue, or sociodemographic characteristics that increase the risk of severe COVID outcomes and that may inform future genetic modifier studies.

COVID-19 and Cancer Linkage Study (COVCan)

Drs. Shiels, Berrington, and Freedman, and Marie-Josèphe Horner, Ph.D., staff scientist, and Eric A. Engels, M.D., M.P.H., chief, in IIB, are collaborating with state health departments to assess the risk of COVID-19 hospitalization and death among cancer patients and survivors, as well as identify patient characteristics and cancer sites exhibiting the strongest associations with severe outcomes. To date, the COVID-19 and Cancer Linkage (COVCan) Study has collected data on 150,000 people with SARS-CoV-2 infection linked to several thousand cancer cases from registries in Connecticut and Maryland. Linkages in several other states are expected in the coming months.

Data Science: Federated Learning across Health Information Exchanges

The Office of the National Coordinator for Health Information Technology reached out to Jonas S. Almeida, Ph.D., chief data scientist, and others in the Data Science Group, for a collaboration building on their work with Health Information Exchanges on federated learning, an artificial intelligence technique where the model parameters can be learned by circulating code through independent data repositories. The non-linear regression procedure is federated instead of the data. Read more about how federated learning is informing the health care response to COVID-19

Providing Guidance and Context to Emerging Research

Ruth Pfeiffer, Ph.D., and Mitchell H. Gail, M.D., Ph.D., both senior investigators in the Biostatistics Branch (BB), are collaborating with investigators in Costa Rica on a study to determine whether patients who recovered from COVID-19 are protected from future infection, compared with individuals without prior infection. A related study, in collaboration with NIAID, will examine factors that influence the spread of infection in a household.

Barry I. Graubard, Ph.D., senior investigator in BB, is working to improve our understanding of seropositivity across the U.S. Those efforts were described in a pre-print publication in January 2021.

Thomas R. O’Brien, M.D., M.P.H., senior investigator, and Sarah Jackson, Ph.D., postdoctoral fellow, in IIB, along with Dr. Prokunina-Olsson, wrote a commentary on the potential benefits and risks of using interferon-lambda to treat COVID-19 disease, published online in April 2020, in Clinical Infectious Disease.

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