RFA-DK-20-021 Mechanistic Studies of SARS-CoV-2/COVID-19 in NIDDK - - PowerPoint PPT Presentation

RFA-DK-20-021 Mechanistic Studies of SARS-CoV-2/COVID-19 in NIDDK Diseases and Organ Systems

Maren R. Laughlin maren.laughlin@nih.gov 301-594-8802 Program Director, Division of Diabetes, Endocrinology and Metabolic Diseases David Saslowsky david.Saslowsky@nih.gov 301-594-8876 Bonnie Burgess-Beusse bonnie.burgess-beusse@nih.gov 301-594-4726 Program Director, Division of Digestive Diseases and Nutrition Ivonne H. Schulman Ivonne.Shulman@nih.gov 301-435-3350 Afshin Parsa Afshin.parsa@nih.gov 301-827-1375 Program Director, Division of Kidney, Urologic, and Hematologic Diseases Xiaodu Guo guox@niddk.nih.gov 301-594-4719 Scientific Review Officer Todd Le LeT@extra.niddk.nih.gov 301-594-7794 Grants Management Specialist Michael Mensah michael.mensah@nih.gov 301-594-3308 Scientific Program Analyst

Background

• Obesity, older age and male sex are all associated with poor

COVID-19 outcomes.

• Diseases, including diabetes (odds ratio 1.48, 16 studies) and

chronic kidney disease (odds ratio 3.25, 9 studies) are associated with a significantly greater risk of mortality from COVID-19. (metanalysis by Paddy Ssentongo et al, PLoS One, August 2020)

• Among other organs, COVID-19 infection is resulting in acute and

possibly chronic damage and dysfunction in heart, kidney and

• liver. (review by Dominik Wolff et al, Infection, August 2020)
• Minority and disadvantaged populations are particularly adversely

affected by COVID-19, with elevated incidence, severity and mortality.

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Purpose

To generate pilot data and establish a strong premise for future studies that will lead to treatment and prevention of severe outcomes in COVID-19 patients with NIDDK diseases, or in tissues of interest to NIDDK.

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RFA-DK-20-021

• Support new basic and clinical mechanistic

research on SARS-CoV-2 and COVID-19 within NIDDK’s interests, including:

Diabetes and other metabolic diseases, obesity, and endocrine, digestive, liver, pancreas, kidney, urological, and hematologic tissues and diseases

• Identify biological mechanisms surrounding:
• Role of pre-existing diseases
• Adverse acute or chronic outcomes in NIDDK tissues /

diseases, including new onset of disease

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RFA-DK-20-021

• Does not support interventional clinical trials
• Applications focused on pathways of viral

infection, invasion, and shedding, without consideration of pathogenic consequences to NIDDK-relevant host organs/tissues/cells will be determined non-responsive to the RFA

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RFA-DK-20-021

Mechanistic Studies of the Interaction between SARS-CoV-2/COVID-19 and Diseases and Organ Systems of Interest to NIDDK (R01 Clinical Trial Optional)

Trans-NIDDK RFA Budget: $250,000 DC/year Issued: July 10, 2020 Duration: 3 years Due: December 16, 2020 $5M/year (11-13 awards) Council: May 2021 Reduced emphasis on preliminary data Will support studies in human subjects or model organisms, using isolated tissues, cells, or in vivo approaches.

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RFA-DK-20-021 Diabetes, Metabolic and Endocrine Diseases

• Mechanisms for any increased susceptibility or altered

course of COVID-19 due to type 1 or type 2 diabetes or diabetic complications;

• Roles of dysregulated glycemia, insulin resistance,

insulin secretion, etc. in severity of response to COVID-19 infection;

• Mechanisms whereby COVID-19 infection results in acute
• r chronic metabolic dysfunction, or the onset of

diabetes or other endocrine diseases;

• Mechanisms involved in alterations in the course of

existing type 1 or type 2 diabetes or the complications

• f diabetes following COVID-19 infection.

RFA-DK-20-021 Obesity and Nutrition

• Tissues, biological systems and pathways involved in

increased susceptibility, greater severity, or diminished response to treatment for COVID-19 in obesity;

• Aspects of adipose tissue biology involved in the

severity of COVID-19 infection, disease course, response to treatment, and outcomes in obesity;

• Mechanisms for impact of nutritional status on variability

in COVID-19 susceptibility, course, and response to treatment;

• Do diet-host-microbiome interactions impact the

course of COVID-19 infection?

RFA-DK-20-021 Digestive Diseases and Liver Diseases

• Mechanisms by which SARS-CoV-2/COVID-19 induces

disease flares, exacerbates disease activity, or contributes to adverse disease outcomes in patients with underlying digestive diseases (including gastrointestinal and liver diseases);

• Determining how SARS-CoV-2 may induce diarrhea,

nausea, and vomiting;

• Does SARS-CoV-2 induce pathology in GI and liver cell

types/organs that express SARS-CoV-2 viral receptors?

• How does SARS-CoV-2 interact with the enteric nervous

system to worsen GI diseases within the mission of the Division of Digestive Diseases and Nutrition or spread to

• ther organs or the central nervous system?

RFA-DK-20-021 Kidney and Urologic Diseases

• Factors and mechanisms by which renal disease portends

worse COVID-19 related morbidity and mortality;

• Factors and mechanisms by which COVID-19 might uniquely

increase the incidence or severity of acute kidney injury;

• Does SARS-CoV2 cause direct kidney injury and if so, to

which cells and by which mechanisms?

• Mechanisms by which COVID-19 may negatively impact

renal function and related outcomes in individuals with renal transplants or glomerulonephritis;

• Effects of COVID-19 on the structure and function of

urologic organs.

RFA-DK-20-021 Hematologic Diseases

• Mechanisms by which COVID-19 and cytokine dysregulation

alter hematopoietic stem and progenitor cell proliferation

• r function (e.g. myeloid blood cell production or tissue

macrophage function);

• Biologic pathways and mechanisms that contribute to a

significantly altered course of COVID-19 sequelae in cohorts

• f inherited cytopenias.

RFA-DK-20-021 Pertaining to HIV/AIDS

• In patients that are co-infected with SARS-CoV-2 and

HIV/AIDS, it is a priority to understand the mechanisms by which organs and tissues that manifest diseases relevant to the NIDDK mission are negatively impacted by SARS-CoV- 2/COVID-19

Frequently Asked Questions

• Can I propose to validate a clinical biomarker for

predicting disease severity?

• No, that would not fall into the realm of mechanistic studies.
• Do I need to include preliminary data?
• No, this RFA doesn’t require preliminary data. However, you

should be able to demonstrate that the project is feasible and will have a significant outcome.

• May I propose a project for 5 years and >$250,000

direct costs/year?

• No, but such a project can be submitted to the normal R01

competition, as long as it has sufficient preliminary data.

RFA-DK-20-021 Mechanistic Studies of SARS-CoV-2/COVID-19 in NIDDK Diseases and Organ Systems

Maren R. Laughlin maren.laughlin@nih.gov 301-594-8802 Program Director, Division of Diabetes, Endocrinology and Metabolic Diseases David Saslowsky david.Saslowsky@nih.gov 301-594-8876 Bonnie Burgess-Beusse bonnie.burgess-beusse@nih.gov 301-594-4726 Program Director, Division of Digestive Diseases and Nutrition Ivonne H. Schulman Ivonne.Shulman@nih.gov 301-435-3350 Afshin Parsa Afshin.parsa@nih.gov 301-827-1375 Program Director, Division of Kidney, Urologic, and Hematologic Diseases Xiaodu Guo guox@niddk.nih.gov 301-594-4719 Scientific Review Officer Todd Le LeT@extra.niddk.nih.gov 301-594-7794 Grants Management Specialist Michael Mensah michael.mensah@nih.gov 301-594-3308 Scientific Program Analyst