The novel coronavirus SARS-CoV-2 or COVID-19 has infected over a million people with approximately 63K deaths in the United States alone (date: April 30, 2020). While little is known about this coronavirus, COVID-19 is known to initiate pathologic inflammation characterized by elevated ferritin and d-dimer, and pro- inflammatory cytokines such as interleukin (IL) -2R, 6, 10 and Tumor Necrosis Factor-alpha (TNF-?), suggesting that mortality might be due to organ failure driven by hyperinflammation. Cancer patients with COVID-19 infection are at about 3.5 times increased risk of developing severe cases and requiring hospitalization, as has been observed at our Houston Methodist Hospital (HMH) and a published report on patients in Wuhan, China. This administrative supplement is designed to gain in-depth insights onto the immune response of cancer vs. non-cancer COVID-19 patients undergoing pilot therapeutic interventions at HMH that has received very positive clinical outcomes: 1- the use of tocilizumab, an anti-IL-6 receptor antibody (Actemra, Genentech, South San Francisco, CA); and 2- a pilot study of applying Single Donor Banked Bone Marrow Mesenchymal Stromal Cells (MSC) for the Treatment of SARS-CoV-2 Induced Acute Respiratory Failure. We propose to determine the inflammation-related markers and cytokine profiles in COVID-19 infected patients following either anti-IL6 receptor tocilizumab antibody or MSC treatments and to establish correlative immune profiles to predict patient eligibility and clinical outcome. Our group is uniquely poised to conduct this study as we have access to more than a thousand samples of blood specimens (plasma and buffy coat cells) from COVID-19 cancer and non-cancer (control) patients. We believe this will help understand the ongoing processes related to both the immunological response in cancer patients affected with the viral infection and how the management of the disease affect that response and ultimately help develop immunotherapies in COVID-19 infected cancer patients.

Public Health Relevance

This administrative supplement application aims to understand the ongoing processes related to both the immunological response in cancer patients affected with the COVID-19 viral infection and how the management of the disease affect that response. Cancer patients represent a high-risk population in this pandemic due to their comorbidities, i.e. age and immunocompromised backgrounds, and are prone to developing severe infection requiring hospitalizations. Given the current lack of our knowledge of this virus and any effective treatment regimens, this proposal seeks to determine cytokines and immune profile after experimental treatment of COVID-19 patients with either Tocilizumab (an interleukin-6 inhibitor) or mesenchymal stem cells (MSCs), both thought to limit the cytokine storm observed in COVID-19 patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54CA210181-05S1
Application #
10161460
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Zahir, Nastaran Z
Project Start
2016-08-29
Project End
2021-07-31
Budget Start
2020-08-17
Budget End
2021-07-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Methodist Hospital Research Institute
Department
Type
DUNS #
185641052
City
Houston
State
TX
Country
United States
Zip Code
77030
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