Foa_Content_of_RFA-IP-24-046 Final.pdf

Centers for Disease Control and Prevention

NATIONAL CENTER FOR IMMUNIZATION AND RESPIRATORY DISEASES

Nationwide Cohort to Estimate Burden of Respiratory Viruses and Immunologic Response (Blood Donor Cohort)

RFA-IP-24-046

02/16/2024

Table of Contents Section I. Funding Opportunity Description

Section II. Award Information

Section III. Eligibility Information

Section IV. Application and Submission Information

Section V. Application Review Information

Section VI. Award Administration Information

Section VII. Agency Contacts

Section VIII. Other Information

Overview Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations Components of Participating Organizations:

National Center for Immunization and Respiratory Diseases Notice of Funding Opportunity (NOFO) Title Nationwide Cohort to Estimate Burden of Respiratory Viruses and Immunologic Response (Blood Donor Cohort) Activity Code U01 – Research Project - Cooperative Agreements

Notice of Funding Opportunity Type New Agency Notice of Funding Opportunity Number

RFA-IP-24-046

Assistance Listings Number(s) 93.083 Category of Funding Activity HL - Health NOFO Purpose This Notice of Funding Opportunity (NOFO) intends to establish and sustain a national, longitudinal cohort of persons completing quarterly surveys and blood collection, with the purpose of monitoring changes in antibody titers against common or novel respiratory virus infections; assessing risk factors for infection, vaccination status, respiratory symptoms and severe illness; and establishing a repository for further analysis as new assays to measure the immune response to respiratory virus infections are developed.

Seroprevalence studies are useful for understanding the proportion of the population with antibodies against a particular pathogen. Because SARS-CoV-2 was a completely novel virus, during the first 1-2 years of the COVID-19 pandemic, CDC was able to use changes in seroprevalence to estimate the cumulative incidence of SARS-CoV-2. A few platforms were large enough to not only estimate changes in seroprevalence nationally, but also stratified by geography, demographic characteristics, and eventually by vaccination status. As the pandemic progressed, high seroprevalence within the overall population limited the utility of ongoing cross-sectional serosurveillance and the program shifted to assessing changes in quantitative antibody titers over time among blood donors with serial longitudinal measures. This revised approach allowed for ongoing assessment of quarterly incident infections and supported studies exploring how individual and population-level immunity related to risk of SARS-CoV-2 infection and/or severe COVID-19 illness.

One of the key advantages of serosurveillance relative to other forms of surveillance is the ability to capture infections that are not diagnosed, including asymptomatic or very mild infections for which the infected person may not have sought testing. This is especially useful when trying to understand the overall burden of respiratory viruses, as often those infected are not tested and most infections with respiratory viruses go unreported. While current surveillance systems for most respiratory viruses are designed to capture the more severe end of the spectrum of illness (e.g., hospital or lab-based surveillance), or to monitor for acute changes in circulation (e.g., wastewater surveillance), they are less useful for understanding the overall burden of disease and how that burden is changing over time.

Serosurveillance also provides an opportunity to characterize population-level immunity against various pathogens and investigate how well antibody titer is predictive of protection from illness, both at the individual and population-level.

As such, this NOFO intends to establish and/or sustain a large-scale national, longitudinal cohort of persons providing quarterly blood samples and linked survey results from each of the nine HHS regions. It would support ongoing monitoring of SARS-CoV-2 and potential monitoring of respiratory syncytial virus (RSV) and influenza incidence and risk. Should the technology (laboratory assays) be available, it could also be expanded to include other respiratory viruses of clinical significance, such as human coronaviruses (HCoVs), human parainfluenza viruses (HPIVs), human metapneumovirus (HMPV), rhinoviruses (RVs)/enteroviruses (EVs), and others. This research NOFO would complement existing surveillance, enhance our understanding of respiratory virus epidemiology, and position us to be able to quickly investigate burden, infection risk, and immunologic response to infection should the country again be faced with the widespread outbreak of a novel pathogen.

Key Dates Publication Date:

To receive notification of any changes to RFA-IP-24-046, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link.

An email address is needed for this service.

Letter of Intent Due Date:

01/16/2024 01/16/2024 https://www.grants.gov/

Application Due Date:

02/16/2024 02/16/2024

On-time submission requires that electronic applications be error-free and made available to CDC for processing from the NIH eRA system on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov no later than 11:59 PM U.S. Eastern Time.

Applicants will use a system or platform to submit their applications through Grants.gov and eRA Commons to CDC. ASSIST, an institutional system to system (S2S) solution, or Grants.gov Workspace are options. ASSIST is a commonly used platform because it provides a validation of all requirements prior to submission and prevents errors.

For more information on accessing or using ASSIST, you can refer to the ASSIST Online Help Site at: https://era.nih.gov/erahelp/assist. Additional support is available from the NIH eRA Service desk via http://grants.nih.gov/support/index.html.

• E-mail: commons@od.nih.gov

• Phone: 301-402-7469 or (toll-free) 1-866-504-9552

• Hours: Monday - Friday, 7 a.m. to 8 p.m. Eastern Time, excluding Federal holidays

Note: HHS/CDC grant submission procedures do not provide a grace period beyond the application due date time to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review:

04/11/2024 Secondary Review:

05/22/2024 Estimated Start Date:

08/01/2024 Expiration Date:

02/17/2024 Required Application Instructions It is critical that applicants follow the instructions in the How to Apply - Application Guide except where instructed to do otherwise in this NOFO. Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Note:The Research Strategy component of the Research Plan is limited to 12 pages.

Page Limitations: Pages that exceed the page limits described in this NOFO will be removed and not forwarded for peer review, potentially affecting an application's score.

http://grants.nih.gov/support/index.html mailto:commons@od.nih.gov https://grants.nih.gov/grants/how-to-apply-application-guide.html

Applications that do not comply with these instructions may be delayed or may not be accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary

• Purpose: This NOFO intends to establish and sustain a national, longitudinal cohort of persons providing quarterly blood samples and link survey results from each of the nine HHS regions to monitor burden of incident infections, population-level immunity against, and individual-level risk factors for, infection with SARS-CoV-2, RSV, influenza, and other respiratory viruses [e.g., human coronaviruses (HCoVs), human parainfluenza viruses (HPIVs), human metapneumovirus (HPMV), rhinoviruses (RVs) and enteroviruses (EVs)].

• Mechanism of Support: U01 Research Project Cooperative Agreement.

• Funds Available and Anticipated Number of Awards: The estimated total funding available, including direct and indirect costs, for the entire five (5)-year project period is $26,500,000. The number of awards will be one (1). Awards issued under this NOFO are contingent upon availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed research will vary from application to application, it is also anticipated that the size and duration of each award may also vary. The total amount awarded and the number of awards will depend upon the number, quality, duration, and cost of the applications received.

• Budget and Project Period: The estimated total funding (direct and indirect) for the first year (12-month budget period) will be $4,500,000 for the first year. The estimated total funding (direct and indirect) for the entire project period will be $26,500,000. The project period is anticipated to run from 08/01/2024 to 07/31/2029.

• Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. “Application and Submission Information” of this announcement.

• Eligible Institutions/Organizations. Institutions/organizations listed in Section III of this announcement are eligible to apply.

• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply. NOTE: CDC does not make awards to individuals directly.

• Number of PDs/PIs. There will only be one PD/PI for each application.

• Number of Applications. Only one application per institution [normally identified by having a unique entity identifier (UEI) number] is allowed.

• Application Type. New

• Application Materials. See Section IV.1 for application materials. Please note that

SF424 (R&R) Form H is to be used when completing the application package. Please see https://grants.nih.gov/grants/how-to-apply-application-guide.html

Section I. Funding Opportunity Description

Statutory Authority Public Health Service Act, Section 317; 42 U.S.C. 247b(k)(1) and 42 U.S.C. 247b(k)(2)

Coronavirus Preparedness and Response Supplemental Appropriations Act, 2020 (P.L. 116-123)

Coronavirus Aid, Relief, and Economic Security Act, 2020 (the “CARES Act”) (P.L. 116-136)

Paycheck Protection Program and Health Care Enhancement Act (P.L. 116-139)

Consolidated Appropriations Act and the Coronavirus Response and Relief Supplement Appropriations Act, 2021 (P.L. 116-260) and/or the American Rescue Plan of 2021 [P.L. 117-2]

1. Background and Purpose Respiratory virus infections are responsible for an extraordinary amount of illness, including both acute morbidity and mortality and long-term morbidity. They have long been recognized as an important cause of hospitalization and death among young children and the elderly.

Secondary analyses of data from the 2019 Global Burden of Disease study estimated that there were over 17 billion cases of upper respiratory infection (representing over 40% of all illness episodes captured in that study) and an additional 489 million cases and 2.5 million deaths due to lower respiratory tract infection that year.

These numbers represent the burden of disease prior to the recent COVID-19 pandemic. Since emerging as a novel respiratory virus, SARS-CoV-2 alone was reported to have caused over 750 million cases and nearly 7 million deaths globally. It was ranked as the third leading cause of death among adults in the US in 2020, 2021, and the fourth leading cause in 2022. However, as with all respiratory virus illnesses, what CDC can capture through surveillance of reported cases, hospitalizations and deaths, likely greatly underestimates the burden. Most infections are not diagnosed or reported. Because testing often does not change management for many respiratory viruses, physicians in the United States are generally discouraged from viral respiratory testing, contributing to the lack of available data to estimate burden. In addition, increases in hospitalization and deaths due to respiratory viruses may occur due to a combination of an increase in the overall number of infections or increased severity per infection; the relative contribution of each of these can be difficult to disentangle without additional data on overall burden of disease.

Early in the COVID-19 pandemic, the CDC began partnering with blood donor organizations and commercial laboratories to perform serosurveillance or testing for antibodies against SARS- CoV-2 to try to better understand the underlying burden of disease. From 2020-2021, CDC worked with partners to use these seroprevalence studies to estimate the total number of people that had been cumulatively infected and/or vaccinated in each state, region, and nationally.

Monthly estimates were posted to CDC Data Tracker for use by public health officials and the public. This data also resulted in high-impact publications that demonstrated how trends in infection and vaccination varied substantially by demographic strata (age, race/ethnicity, region), and how much routine surveillance under-estimated the total burden of infections. By the end of 2021, these seroprevalence studies showed that nearly 30% of the country had been infected with SARS-CoV-2 and over 90% had antibodies that demonstrated a history of either infection or vaccination.

Due to high seroprevalence and an increasing frequency of reinfection with SARS-CoV-2, a change in methodology was needed to estimate incidence of infections and changes in population immunity. In 2022, the CDC updated their blood donor seroprevalence approach to focus on assessment of antibody changes over time in a large cohort of individuals (about 140,000) that provided multiple blood donations per year. Assessing longitudinal quantitative antibody levels among this repeat blood donor cohort achieved multiple aims, including: 1) providing greater insight into antibody waning and how this is affected by repeat infections and vaccinations; 2) enabling the assessment of incidence of reinfections through measurement of boosting in antibody titers over time; 3) enabling assessment of quantitative antibodies as a correlate of protection against infection (including reinfection) and potentially severe disease; and 4) supporting analysis of vaccine effectiveness against serologic evidence of infection and reinfection.

Understanding the underlying burden and changes in population immunity to SARS-CoV-2 and other respiratory viruses infections will continue to be important as these viruses continue to evolve and as new products to reduce the risk of infection and severe disease are released. This information is critical for calculating absolute risks of respiratory virus disease and deaths following infection (e.g., assessing if increases in hospitalizations are from increases in infections vs. an increases risk of severe disease if infected), monitoring population-level immunity, and further assessing the impact of mitigation measures such as vaccination. If feasible, expanding the approach that has been used for SARS-CoV-2 to other respiratory viruses (e.g., RSV, influenza, HCoVs, HPIVs, HPMV, and RV/EVs) will provide greater insight into the burden and risk factors for respiratory viral infections overall, add context to existing surveillance systems, and provide a platform of more in-depth assessments of the human immunologic response to these ubiquitous infections.

Health Equity:

CDC supports efforts to improve the health of populations disproportionately affected by infectious diseases by maximizing the health impact of public health services, reducing disease incidence, and advancing health equity.

A health disparity occurs when a health outcome is seen to a greater or lesser extent between populations. Health disparities in infectious diseases are inextricably linked to a complex blend of social determinants that influence which populations are most disproportionately affected by these infections and diseases.

Social determinants are conditions in the places where people live, learn, work, and play that affect a wide range of health and quality-of life-risks and outcomes (https://www.cdc.gov/socialdeterminants/index.htm). These include conditions for early childhood development; education, employment, and work; food security, health services, housing, income, and social exclusion. Health equity is a desirable goal that entails special efforts to improve the health of those who have experienced social or economic challenges. It requires:

• Continuous efforts focused on elimination of health disparities, including disparities in health and in the living and working conditions that influence health, and

• Continuous efforts to maintain a desired state of equity after health disparities are eliminated.

Applicants should use data, including social determinants data, to identify communities within their jurisdictions that are disproportionately affected by infectious diseases and related diseases https://www.cdc.gov/socialdeterminants/index.htm and conditions, and plan activities to help eliminate health disparities. In collaboration with partners and appropriate sectors of the community, applicants should consider social determinants of health in the development, implementation, and evaluation of specific efforts and use culturally appropriate interventions and strategies that are tailored for the communities for which they are intended.

Healthy People 2030 and other National Strategic Priorities This NOFO will focus on improving U.S. preparedness to respond to public health emergencies including the ongoing potential for the introduction or evolution of novel respiratory viruses of pandemic potential, through establishing a longitudinal cohort of persons providing quarterly blood samples, through whom CDC can monitor the burden of disease and immunologic response to respiratory viral infections nationally and within each of the nine HHS regions. As such, this NOFO supports the following Health and Human Service (HHS) Strategic Plan topic areas:

Strategic Goal 2: Safeguard and Improve National and Global Health Conditions and Outcomes

Strategic Objective 2.1: Improve capabilities to predict, prevent, prepare for, respond to, and recover from disasters, public health and medical emergencies, and threats across the nation and globe.

Strategic Goal 4: Restore Trust and Accelerate Advancements in Science and Research for All

Strategic Objective 4.2: Invest in the research enterprise and the scientific workforce to maintain leadership in the development of innovations that broaden our understanding of disease, healthcare, public health, and human services resulting in more effective interventions, treatments, and programs.

Strategic Objective 4.3: Strengthen surveillance, epidemiology, and laboratory capacity to understand and equitably address diseases and conditions.

Strategic Objective 4.4: Improve data collection, use, and evaluation, to increase evidence-based knowledge that leads to better health outcomes, reduced health disparities, and improved social well-being, equity, and economic resilience.

Public Health Impact Use of serosurveillance to measure burden has the strategic advantage of not requiring the infected person to have sought clinical care or received a diagnosis. Serosurveillance also provides an opportunity to characterize population-level immunity against various pathogens and investigate how well antibody titers predict protection from illness, both at the individual and population-level.

While emerging from the COVID-19 pandemic, understanding the burden and evolution of population immunity to SARS-CoV-2 infections will continue to be important. Expanding this approach to further characterize RSV, influenza, and other respiratory viruses will enhance CDC understanding of the burden and risk factors for respiratory viral infections overall, adding context to existing surveillance systems.

These activities support multiple strategic priorities within CDC, including:

https://www.hhs.gov/about/strategic-plan/2022-2026/goal-2/objective-2-1/index.html https://www.hhs.gov/about/strategic-plan/2022-2026/goal-4/objective-4-2/index.html https://www.hhs.gov/about/strategic-plan/2022-2026/goal-4/objective-4-3/index.html https://www.hhs.gov/about/strategic-plan/2022-2026/goal-4/objective-4-4/index.html

Coronavirus and other Respiratory Viruses Division (CORVD) Strategic Priority (Coronavirus and Other Respiratory Viruses Division (CORVD) | NCIRD | CDC)

• Track and study respiratory viruses through surveillance, lab tests, and epidemiologic studies on infection, outcomes, and the efficacy of treatment and prevention

National Center for Immunization and Respiratory Disease (NCIRD) Strategic Priority (Office of the Director (OD) | NCIRD | CDC):

• Improve prevention, detection, and control of respiratory disease threats, including

COVID-19

CDC 2022-2027 Strategic Plan: Advancing Science and Health Equity (Core Capabilities (cdc.gov))

• Develop and deploy world-class data and analytics

• Build on the current foundation for strong global health capacity and domestic preparedness.

Relevant Work As noted above, CDC developed contracts to implement routine national-level serosurveillance of SARS-CoV-2 infection and vaccination during the COVID-19 pandemic. Data description of and results of these studies have been posted on CDC COVID-19 websites and data tracker (CDC COVID Data Tracker: Antibody Seroprevalence).

In addition, these studies resulted in multiple high-impact publications that further explored risk factors for infection, trends in infections and population-level immunity over time, and multiple other related topics. A sample of some of the key publications from this previous work include:

1. Estimates of SARS-CoV-2 Seroprevalence and Incidence of Primary SARS-CoV-2 Infections Among Blood Donors, by COVID-19 Vaccination Status — United States, April 2021–September 2022 | MMWR (cdc.gov)

2. Estimated SARS-CoV-2 antibody seroprevalence trends and relationship to reported case prevalence from a repeated, cross-sectional study in the 50 states and the District of Columbia, United States—October 25, 2020–February 26, 2022 - PMC (nih.gov)

3. Seroprevalence of Infection-Induced SARS-CoV-2 Antibodies — United States, September 2021–February 2022 | MMWR (cdc.gov)

4. Estimated SARS-CoV-2 antibody seroprevalence trends and relationship to reported case prevalence from a repeated, cross-sectional study in the 50 states and the District of Columbia, United States—October 25, 2020–February 26, 2022 - PMC (nih.gov)

5. How do we…form and coordinate a national serosurvey of SARS-CoV-2 within the blood collection industry? - PubMed (nih.gov)

6. Updated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Estimates Based on Blood Donations, July 2020-December 2021 | Vaccination | JAMA | JAMA Network

7. Coronavirus Disease 2019 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection in the United States Before the Delta- and Omicron- Associated Surges: A Retrospective Cohort Study of Repeat Blood Donors | The Journal of Infectious Diseases | Oxford Academic (oup.com) https://www.cdc.gov/ncird/careers/corvd.html https://www.cdc.gov/ncird/careers/corvd.html https://www.cdc.gov/ncird/careers/office-director.html https://www.cdc.gov/ncird/careers/office-director.html https://www.cdc.gov/about/strategic-plan/capacity-priority.html https://www.cdc.gov/about/strategic-plan/capacity-priority.html https://www.cdc.gov/surveillance/projects/dmi-initiative/index.html https://covid.cdc.gov/covid-data-tracker/?CDC_AA_refVal=https%25%203A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fcases-in-us.html#antibody-seroprevalence https://www.cdc.gov/mmwr/volumes/72/wr/mm7222a3.htm?s_cid=mm7222a3_w https://www.cdc.gov/mmwr/volumes/72/wr/mm7222a3.htm?s_cid=mm7222a3_w https://www.cdc.gov/mmwr/volumes/72/wr/mm7222a3.htm?s_cid=mm7222a3_w https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716971/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716971/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716971/ https://www.cdc.gov/mmwr/volumes/71/wr/mm7117e3.htm https://www.cdc.gov/mmwr/volumes/71/wr/mm7117e3.htm https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716971/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716971/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716971/ https://pubmed.ncbi.nlm.nih.gov/35607854/ https://pubmed.ncbi.nlm.nih.gov/35607854/ https://jamanetwork.com/journals/jama/fullarticle/2793517 https://jamanetwork.com/journals/jama/fullarticle/2793517 https://jamanetwork.com/journals/jama/fullarticle/2793517 https://academic.oup.com/jid/article/226/9/1556/6654836?login=true https://academic.oup.com/jid/article/226/9/1556/6654836?login=true https://academic.oup.com/jid/article/226/9/1556/6654836?login=true https://academic.oup.com/jid/article/226/9/1556/6654836?login=true

8. Analysis of serological surveys of antibodies to SARS-CoV-2 in the United States to estimate parameters needed for transmission modeling and to evaluate and improve the accuracy of predictions - ScienceDirect

9. Association of Trends in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) Seroprevalence and State-Issued Nonpharmaceutical Interventions: United States, 1 August 2020 to 30 March 2021 | Clinical Infectious Diseases | Oxford Academic (oup.com)

10. Population-Weighted Seroprevalence From Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, Vaccination, and Hybrid Immunity Among US Blood Donations From January to December 2021 | Clinical Infectious Diseases | Oxford Academic (oup.com)

11. Use of US Blood Donors for National Serosurveillance of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program | Clinical Infectious Diseases | Oxford Academic (oup.com)

12. Seasonal coronavirus protective immunity is short-lasting | Nature Medicine

Additional Background Articles of Relevance:

1. Global burden of upper respiratory infections in 204 countries and territories, from 1990 to 2019 (thelancet.com)

2. Trends in the global burden of lower respiratory infections: the knowns and the unknowns (thelancet.com)

3. WHO Coronavirus (COVID-19) Dashboard | WHO Coronavirus (COVID-19) Dashboard With Vaccination Data

4. COVID-19 Data Review: Update on COVID-19–Related Mortality | CDC

5. Provisional Mortality Data — United States, 2022 | MMWR (cdc.gov)

2. Approach Whenever possible, applications should include objectives written in SMART format (e.g., Specific, Measurable, Achievable, Realistic, and Time-bound)

This NOFO intends to establish and sustain a national, longitudinal cohort of over 20,000 persons providing quarterly blood samples linked with survey responses, with over 2,000 participants from each of the nine (9) HHS regions. Routinely donated blood specimen from this cohort would be used to assess and describe how the prevalence and magnitude of antibodies against common respiratory viruses change over time, among US adults. It is expected that application should include plans to enroll demographically and geographically diverse participants.

Applications should demonstrate their ability to accomplish the following activities:

• Establishment of a national, longitudinal cohort of persons providing quarterly blood samples and linked survey results.

• Antibody testing and specimen storage.

• Development and implementation of participant surveys.

• Data management, analysis, and sharing of the data with CDC.

• Timely dissemination of findings to inform public health policy and implementation.

https://www.sciencedirect.com/science/article/pii/S0022519322002879?via%3Dihub https://www.sciencedirect.com/science/article/pii/S0022519322002879?via%3Dihub https://www.sciencedirect.com/science/article/pii/S0022519322002879?via%3Dihub https://academic.oup.com/cid/article/75/Supplement_2/S264/6605073?login=true https://academic.oup.com/cid/article/75/Supplement_2/S264/6605073?login=true https://academic.oup.com/cid/article/75/Supplement_2/S264/6605073?login=true https://academic.oup.com/cid/article/75/Supplement_2/S264/6605073?login=true https://academic.oup.com/cid/article/75/Supplement_2/S254/6605072?login=true https://academic.oup.com/cid/article/75/Supplement_2/S254/6605072?login=true https://academic.oup.com/cid/article/75/Supplement_2/S254/6605072?login=true https://academic.oup.com/cid/article/75/Supplement_2/S254/6605072?login=true https://academic.oup.com/cid/article/74/5/871/6296028?login=true https://academic.oup.com/cid/article/74/5/871/6296028?login=true https://academic.oup.com/cid/article/74/5/871/6296028?login=true https://www.nature.com/articles/s41591-020-1083-1 https://www.thelancet.com/action/showPdf?pii=S2589-5370%2821%2900266-2 https://www.thelancet.com/action/showPdf?pii=S2589-5370%2821%2900266-2 https://www.thelancet.com/action/showPdf?pii=S1473-3099%2822%2900445-5 https://www.thelancet.com/action/showPdf?pii=S1473-3099%2822%2900445-5 https://covid19.who.int/ https://covid19.who.int/ https://www.cdc.gov/coronavirus/2019-ncov/science/data-review/index.html https://www.cdc.gov/mmwr/volumes/72/wr/mm7218a3.htm

1. Establishing national, longitudinal cohort of persons providing quarterly blood samples and linked survey results:

Applications should demonstrate the ability to establish a large-scale longitudinal cohort of individuals with serologic specimens available from multiple time points throughout the implementation year. Previous iterations of this approach have included cohorts of over 140,000 individuals, which allowed us to calculate granular state-based prevalence and incidence measures. While the population included in this cohort may be smaller, the applications should demonstrate that at a minimum the sample will be sufficient for national and regional burden estimates across a range of respiratory viruses, and demographic groups (e.g., age, race, ethnicity) at least quarterly. Applicants should plan to enroll a cohort of participants that are diverse, both geographically and demographically. A history of running/maintaining a similar large-scale cohort with routine blood samples and laboratory testing linked with timely survey data is required.

2. Antibody testing and specimen storage.

Quantitative antibody testing for multiple respiratory viruses will be a key feature of this scientific platform in order to support the objectives of measuring incident infections, tracking changes in population-level immunity, and assessing correlates of protection. Qualitative testing would only be considered for targeted studies and for viruses, for which quantitative testing is not available.

For SARS-CoV-2, testing is expected to include quantitative assays that measure antibody titers against both nucleocapsid (infection only) and spike (vaccination or infection) antigens.

Specimen should be available with adequate frequency to calculate incident infections based on changes in antibody titers and measure trends in median antibody titers quarterly. This approach has been used for SARS-CoV-2 in multiple settings but translating this approach to other respiratory viruses (e.g., RSV, influenza, HCoVs, HPIVs, HPMV, and RV/EVs) will likely require initial exploration and analysis in order to determine what assays could be used and thresholds of changes (i.e., boosting) that would likely indicate a new infection or exposure. The application should include a proposal for the type of testing that will be used in the submission.

Recipients will ultimately work with CDC to finalize the choice of assays.

Applicants should either possess the laboratory capacity or propose a laboratory that they would subcontract in order to perform most of the high-volume testing needed to accomplish the main objectives of this project. Real-time testing will be important to allow rapid dissemination of results. Adequate storage to set up a large multi-year specimen bank would also be important.

Applicants should indicate if they are prepared to send samples to CDC in the event that 1) a specific assay is more readily available at CDC or 2) there would be a benefit from collaborating directly with the CDC laboratory or running additional analyses on collected/stored specimen.

3. Development and implementation of participant surveys

Cohort participants should be routinely surveyed on variables of interest including:

• Demographic data (sex, age, race, ethnicity, zip code, date of donation) to support risk factor analyses, but also to support weighting of the data.

• History of recent upper or lower respiratory infections and associated symptoms

• Testing and healthcare seeking behaviors, including level of care sought or required.

• Recent history of laboratory-confirmed diagnoses of respiratory virus infections, including both rapid/antigen and NAAT testing performed at a healthcare setting, home, or other setting.

• Clinical and non-clinical outcomes of infection including hospitalization, loss of work, school absences, functional limitations, and/or ongoing symptoms following infection.

• Uptake/use of both preventive (e.g., vaccination or monoclonal antibody), and treatment (e.g., antiviral) measures, including non-pharmaceutical interventions when appropriate.

Some questions may occur quarterly and others annually. The content of the questionnaire will be created in collaboration with CDC and will undergo all required approval processes.

4. Data management, analysis, and sharing.

Applicants should demonstrate that they have adequate personnel and systems to manage the large amount of data that will be accrued over the course of this project. Applicants should describe their data management and storage systems and processes. These should include processes to safeguard data and maintain confidentiality. As well, they should describe the planned approach for data cleaning, routine sharing of full de-identified datasets with CDC, and the creation of analytic data sets.

Data analysis tasks may be shared between CDC and the award recipient, though the application should provide an overview of their analytic approach and the personnel that would support this, which could include subcontracts if appropriate. Analyses of antibody test results of the blood donation specimens in combination with the questionnaires to confirm vaccination and/or infection history should allow the applicant to: 1) track rates of new infections (primary infections and reinfections) among cohort participants, including those with a history or prior infection and/or vaccination; 2) inform stability/waning of antibody titers over time following infection and vaccination, including among persons with multiple exposures (e.g. booster vaccines and reinfections); 3) allow ongoing assessment of serological correlates of protection, including from vaccine breakthrough infections and reinfections; and 4) inform real-world studies assessing the effectiveness of pharmacologic (e.g. vaccine) and non-pharmacologic preventive measures. Weighting or other analytic techniques should be used to make results as generalizable to overall U.S. population as possible.

5. Dissemination of findings:

Applicants are expected to be responsible for ensuring all activities receive either non-research determination or IRB review and approval by their associated review boards. Study investigators will be responsible for ensuring protection against risks, including protection of confidentiality, monitoring participant safety, and complying with all reporting requirements. The applicant study team will provide oversight of all study procedures and quality assurance checks and will actively monitor the integrity of the data collection, adherence to the study protocol, and ongoing safety of participants.

CDC clearance will be required prior to initiating study procedures or publishing or disseminating results. Results will also be communicated at scientific meetings and in publications, following appropriate procedures to obtain clearance from CDC and all relevant IRBs.

This NOFO may fund health information systems infrastructure, including workforce and public health laboratories, to support the specific strategies, activities, and outcomes described in this

NOFO.

Objectives/Outcomes The following objectives will be accomplished for SARS-CoV-2 using established methodologies. Similar objectives will be pursued for RSV, influenza, and other respiratory viruses (e.g., HCoVs, HPIVs, HPMV, and RV/EVs) as the technology and science allows:

• Estimate incidence of infection among adults nationally using seroconversion or changes in antibody titers among a weighted sample of cohort participants.

• Estimate infection incidence by geographic area (HHS region) and within demographic subgroups (e.g., by race/ethnicity, sex, age group).

• Assess demographic and other risk factors for infection in the setting of evolving underlying immunity and the emergence of new viruses/variants.

• Determine antibody thresholds for protection against symptomatic infection (including from newly circulating variants).

• Assess state- or region-specific population-level immunity to/risk for infection through tracking median antibody titers within various populations.

• Monitor waning immunity and measure ability to neutralize variants with novel mutations following administration of the most up-to-date vaccines.

• Use surveys or other instruments to determine if blood donors have been vaccinated, experienced symptoms or severe illness, or to determine respiratory virus prevention behaviors or estimate level of exposure to viruses.

• Use surveys or other instruments to assess vaccine uptake and attitudes towards new respiratory virus vaccines, prophylactic medications, and/or therapeutics.

• Monitor ongoing and new symptoms following respiratory virus infection to estimate prevalence of post-acute syndromes based on self-report of symptoms; potentially stratified by reported vaccination status and timing of infection.

• Establish repository of nationally representative samples at CDC for the purpose of investigating the prevalence, risk factors for, or presentation of novel respiratory viruses.

Target Population The award recipient of this NOFO will be expected to establish and maintain a longitudinal cohort of at least 20,000 persons who are routinely providing blood samples nationally, in order to support quarterly assessment of antibody prevalence, median antibody titer, and incidence of infection nationally.

While state-specific incident and burden measures are preferred, the applicant should plan to enroll at least 2,000 persons in each HHS region, to ensure the ability to obtain quarterly estimates in each region for a range of respiratory viruses. This sample size should be sufficient to measure quarterly incidence of respiratory virus infection within +/- 1.5% if the incidence falls between 2-15%.

In addition, the applicant should ensure that the sample size is sufficient to assess each of the primary objectives stratified by multiple demographic factors (e.g., age group, sex, race, and ethnicity). It will be important to ensure adequate enrollment of potentially under-represented demographic groups, e.g., by race/ethnicity (non-Hispanic Black, Hispanic, Asian) and across adult age groups (18-24, 25-49, 50-64, and 65+).

Applicants should provide a sample size justification of their own that demonstrates that their sampling plan has adequate power (over 80%) to measure each of these objectives with reasonable precision (for 95% confidence intervals) in each HHS region and by demographic subgroup.

Collaboration/Partnerships Applicants should work closely with any subcontractors proposed to develop their application.

Evaluation/Performance Measurement The application should include measurable goals and aims based on a five (5) year research project period. The application should describe specific, measurable, achievable, realistic, and time-phased (SMART) project objectives for each activity described in the application project plan and describe the development and implementation of project performance measures based on specific programmatic objectives.

The application should include an evaluation/performance measurement plan. Progress should be identified by achievement of relevant milestones which may include, but are not limited to:

• The type of evaluations (i.e., process, outcome, or both) to be conducted.

• Key evaluation questions.

• Other information (e.g., performance measures to be developed by the applicant).

Recipients will be expected to meet regularly with CDC, at a minimum monthly, but potentially more often if needed, to review progress on project design, implementation, and completion of key objectives.

Translation Plan The applicant should submit a plan describing how the findings and outcomes will be translated for: 1) sharing with the public, 2) informing policy, and 3) informing the medical and scientific communities.

This information should be understandable to a variety of audiences, including policymakers, practitioners, public health programs, healthcare institutions, professional organizations, community groups, researchers, and other potential end users.

3. Funding Strategy Coronavirus Disease 2019 (COVID-19) Funds: A recipient of a grant or cooperative agreement awarded by the Department of Health and Human Services (HHS) with funds made available under the Coronavirus Preparedness and Response Supplemental Appropriations Act, 2020 (P.L. 116-123); the Coronavirus Aid, Relief, and Economic Security Act, 2020 (the “CARES Act”) (P.L. 116-136); the Paycheck Protection Program and Health Care Enhancement Act (P.L. 116-139); the Consolidated Appropriations Act and the Coronavirus Response and Relief Supplement Appropriations Act, 2021 (P.L. 116-260) and/or the American Rescue Plan of 2021 [P.L. 117-2] agrees, as applicable to the award, to: 1) comply with existing and/or future directives and guidance from the Secretary regarding control of the spread of COVID-19; 2) in consultation and coordination with HHS, provide, commensurate with the condition of the individual, COVID-19 patient care regardless of the individual home jurisdiction and/or appropriate public health measures (e.g., social distancing, home isolation); and 3) assist the United States Government in the implementation and enforcement of federal orders related to quarantine and isolation.

In addition, to the extent applicable, Recipient will comply with Section 18115 of the CARES Act, with respect to the reporting to the HHS Secretary of results of tests intended to detect SARS–CoV–2 or to diagnose a possible case of COVID–19. Such reporting shall be in accordance with guidance and direction from HHS and/or CDC. HHS laboratory reporting guidance is posted at: https://www.hhs.gov/sites/default/files/covid-19-laboratory-data-reporting-guidance.pdf.

Further, consistent with the full scope of applicable grant regulations (45 C.F.R. 75.322), the purpose of this award, and the underlying funding, the recipient is expected to provide to CDC copies of and/or access to COVID-19 data collected with these funds, including, but not limited to data related to COVID-19 testing. CDC will specify in further guidance and directives what is encompassed by this requirement.

This award is contingent upon agreement by the recipient to comply with existing and future guidance from the HHS Secretary regarding control of the spread of COVID-19. In addition, recipient is expected to flow down these terms to any subaward, to the extent applicable to activities set out in such subaward.

Section II. Award Information Funding Instrument Type:

CA (Cooperative Agreement) A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed:

New - An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round.

Estimated Total Funding:

$26,500,000 The estimated total funding (direct and indirect costs) for the first budget period is $4,500,000.

The estimated total funding (direct and indirect costs) for the entire project period is $26,500,000.

Year 1: $4,500,000

Year 2: $5,500,000

Year 3: $5,500,000

Year 4: $5,500,000

Year 5: $5,500,000 https://www.hhs.gov/sites/default/files/covid-19-laboratory-data-reporting-guidance.pdf https://www.hhs.gov/sites/default/files/covid-19-laboratory-data-reporting-guidance.pdf

Anticipated Number of Awards:

Awards issued under this NOFO are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Award Ceiling:

$4,500,000 Per Budget Period

Award Floor:

$3,000,000 Per Budget Period

Total Period of Performance Length:

5 year(s)

Throughout the Period of Performance, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this NOFO.

If you are successful and receive a Notice of Award, in accepting the award, you agree that the award and any activities thereunder are subject to all provisions of 45 CFR Part 75, currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category:

00 (State governments)

01 (County governments)

02 (City or township governments)

04 (Special district governments)

05 (Independent school districts)

06 (Public and State controlled institutions of higher education)

07 (Native American tribal governments (Federally recognized))

08 (Public housing authorities/Indian housing authorities) https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf

11 (Native American tribal organizations (other than Federally recognized tribal governments))

12 (Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education)

13 (Nonprofits without 501(c)(3) status with the IRS, other than institutions of higher education)

20 (Private institutions of higher education)

22 (For profit organizations other than small businesses)

Additional Eligibility Category:

The following types of Higher Education Institutions are always encouraged to apply for CDC support as Public or Private Institutions of Higher Education:

Hispanic-serving Institutions

Historically Black Colleges and Universities (HBCUs)

Tribally Controlled Colleges and Universities (TCCUs)

Alaska Native and Native Hawaiian Serving Institutions

Nonprofits (Other than Institutions of Higher Education):

Nonprofits (Other than Institutions of Higher Education)

Other:

Faith-based or Community-based Organizations

Regional Organizations

2. Foreign Organizations Foreign Organizations are not eligible to apply.

Foreign components of U.S. Organizations are not eligible to apply.

For this announcement, applicants may not include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Additional Information on Eligibility

4. Justification for Less than Maximum Competition N/A

5. Responsiveness N/A

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Unique Entity Identifier (UEI) number in order to begin each of the following registrations.

PLEASE NOTE: Effective April 4, 2022, applicants must have a Unique Entity Identifier (UEI) at the time of application submission. The UEI replaced the Data Universal Numbering System (DUNS) and is generated as part of SAM.gov registration. Current SAM.gov registrants have already been assigned their UEI and can view it in SAM.gov and Grants.gov. Additional information is available on the GSA website, SAM.gov, and Grants.gov-Finding the UEI.

• (Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: NCAGE Tool / Products / NCS Help Center (nato.int).

• System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, SAM.gov.

• Grants.gov

• eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes. The one-time registration process will take three to five days to complete.

However, it is best to start the registration process at least two weeks prior to application submission.

All Senior/Key Personnel (including Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing Principal Investigator (PD/PI) eRA…