Research Initiatives on COVID-19 in the Division of the National Toxicology Program

National Institute Of Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

Study 1. We have begun to assess the innate and adaptive immune responses and investigate specific cellular functions that have been demonstrated to be relevant to respiratory viral infection, including (influenza and SARS-CoV-2), susceptibility and pathogenesis by evaluating inflammatory and immune responses. We are using an in vitro human whole blood assay system that can examine the impact of environmental factors on lymphocyte cytotoxicity as well as selected immune functions from the same cell cultures and using multiple donors. To provide direct relevance to respiratory viral infections, we have incorporated evaluation of immune responses to viral antigens. Study 2. To investigate interindividual susceptibility factors, human donors with a prior history of respiratory viral disease will be screened using the in vitro assays for immune response and challenge with viral antigens to provide information on the potential interactions with age, gender, and ethnicity. NICEATM and NC3Rs co-hosted a Spring Workshop (virtual) for the MPSCoRe working group. Meeting attendees were individuals and organizations that represent MPS stakeholders as well as COVID researchers. The agenda featured talks from two sessions, MPS Models for Testing Therapeutics and MPS Models for Understanding Disease Mechanisms, followed by a Roundtable discussion. The MPSCoRe working group identified the need for high-quality study data to evaluate MPS technologies for COVID-19 studies. The University of Pittsburgh has developed a MPS Database (MPSDb), which aggregates MPS data with linked preclinical and clinical databases for analysis in the context of human exposure. NICEATM provided support for the development of a COVID-19 portal within the MPSDb, which provides links to COVID-19 disease information from Government and literature sources. This includes links to disease statistics, strategic responses, funding information, COVID-19 literature hubs and other scientific literature sites pre-queried for COVID-19. NICEATM also provided input and guidance on the overall design and coordination for a validation study of a MPS to evaluate the potential efficacy of prospective COVID-19 therapeutics prior to their study in a clinical setting. NICEATM and NC3Rs co-hosted a Summer Webinar Series (virtual, once per month from June through September 2021) for the MPSCoRe working group members. Each agenda featured talks from two working group members and/or other invited MPS stakeholders or COVID researchers. Study 3. We have been working with NC-DHHS to obtain the appropriate datasets. A data delivery was done, however, it did not contain the needed temporal data, so an amendment was added. This amendment has delayed the reception of the final working dataset.