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Issued by

Office of Research on Women's Health (ORWH)

Purpose

The National Institutes of Health (NIH) Office of Research on Women’s Health (ORWH), in partnership with the NIH Coordinating Committee on Research on Women’s Health (CCRWH), is publishing this request for information (RFI) to seek public comments/input on research gaps, clinical practice needs, and research opportunities to inform research priority setting at the intersection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pandemic and/or post-acute sequelae of SARS-CoV-2 infection (PASC), aka long COVID, and the health of women.

Background

In September 1990, ORWH was established by then–NIH Acting Director William F. Raub, Ph.D., and the office was established in statute by the NIH Revitalization Act of 1993 (Public Law 103–43, Section 486) to ensure that women’s health is part of the NIH scientific framework and supported throughout the biomedical enterprise. Women account for over half of the U.S. population, and a complex intersection of forces affects disease risk and presentation, treatment outcomes, and health-related quality of life for humans across the life course. To ensure that scientific progress benefits the entire population, ORWH works collaboratively with other NIH Institutes, Centers, and Offices (ICOs) to stimulate basic, clinical, and translational research on the role of sex and gender in health and disease and to promote both the application of a multidimensional research framework and the incorporation of an intersectionality lens into research priorities in women’s health, as highlighted in the 2019–2023 Trans-NIH Strategic Plan for Women’s Health Research.¹

The Rationale for the RFI

From the beginning of the SARS-CoV-2/COVID-19 pandemic, surveillance data illustrated sex differences in infection and mortality rates, with infection rates being higher in females (52.8%) but disease severity and mortality being higher in males.² These clinical outcomes of SARS-CoV-2 infection/COVID-19 highlight sex differences in the immune response.³ These differences prompted ORWH to develop, collaboratively with ICOs, a guiding principles document⁴ to complement the 2021 NIH-Wide Strategic Plan for COVID-19 Research⁵ and aid the research community in considering the range of biological and social factors relevant to COVID-19 and the health of women (e.g., the susceptibility of pregnant and menopausal individuals to severe COVID-19 outcomes).⁶ Furthermore, a study showed sex disparities in U.S. SARS-CoV-2 infections/COVID-19 to be modest and appear to vary in respect to context-sensitive variables, including health behaviors, health status, occupation, and other social identifiers.⁷ This RFI is seeking comments on research gaps and opportunities specific to health consequences of SARS-CoV-2 infection/COVID-19 and PASC (long COVID) at the intersection of women’s health concerns—including, but not limited to, sex and gender differences, reproductive health issues, circumstances of domestic violence or intimate partner violence (IPV), and diseases such as cancer, cardiovascular disease, pulmonary disease, obesity, metabolic conditions, mental health conditions, and substance use disorders. Input regarding persistent symptoms after acute infection and/or pathology in multiple organ systems leading to adverse health outcomes in women is also encouraged. A few predictors of severe infections and PASC in women include, but are not limited to, fatigue, anosmia, and dysgeusia.⁸ Additionally, input regarding women’s health consequences, research gaps, and opportunities with the introduction and acceptance of the SARS-CoV-2/COVID-19 vaccines is also being solicited as part of this effort.

References

1. The 2019–2023 Trans-NIH Strategic Plan for Women’s Health Research. https://orwh.od.nih.gov/sites/orwh/files/docs/ORWH_Strategic_Plan_2019_508C_0.pdf

2. Demographic Trends of COVID-19 cases and deaths in the US reported to CDC. https://covid.cdc.gov/covid-data-tracker/#demographics

3. Takahashi T, Ellingson MK, Wong P, et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. Dec 2020;588(7837):315–320. doi:10.1038/s41586-020-2700-3

4. Guiding Principles: Sex and gender influences in COVID-19 and the health of women. https://orwh.od.nih.gov/sites/orwh/files/docs/ORWHGuidingPrinciple.pdf

5. NIH-Wide Strategic Plan for COVID-19 Research https://covid19.nih.gov/sites/default/files/2021-05/NIH-Wide-COVID-19-StratPlan_2021_508_1.pdf

6. Ellington S, Strid P, Tong VT, et al. Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22-June 7, 2020. MMWR Morb Mortal Wkly Rep. Jun 26 2020;69(25):769–775. doi:10.15585/mmwr.mm6925a1

7. Danielsen AC, Lee KM, Boulicault M, et al. Sex disparities in COVID-19 outcomes in the United States: Quantifying and contextualizing variation. Soc Sci Med. Jan 10 2022;294:114716. doi:10.1016/j.socscimed.2022.114716

8. Knight DRT, Munipalli B, Logvinov, II, et al. Perception, Prevalence, and Prediction of Severe Infection and Post-acute Sequelae of COVID-19. Am J Med Sci. Jan 8, 2022. doi:10.1016/j.amjms.2022.01.002

Information Requested

NIH seeks information and actionable guidance on research gaps, needs, and opportunities related to the intersection of the SARS-CoV-2/COVID-19 pandemic and/or post-acute sequelae of SARS-CoV-2 infection (PASC), aka long COVID, and women’s health. Responses are welcome from the scientific community, clinicians, academic institutions, professional societies, health care organizations, patients, community organizations, patient advocacy groups, and the general public.

Public comment is sought for, but not limited to the following:

• Specific conditions, disorders, or health-related events which are more prevalent in women that are affected or altered by SARS-CoV-2/COVID-19 and/or PASC or confer risk to acute/severe complications to infection or adverse events related to therapies. In addition, consider the if these conditions differ across age groups, races/ethnicities, or associations with pre-existing conditions.
• Scientific gaps or areas with opportunity to discover mechanisms of acute or chronic PASC (long COVID) response to infection throughout women’s life course (including pregnancy and postpartum) and in women of different races/ethnicities/origins/heritage groups. In addition, consider how these mechanisms (of disease or resilience) interact with environmental factors, including behavioral, psychosocial, socioeconomic, and sociocultural determinants of health.
• Strategic approaches to enhance inclusion of women of diverse backgrounds in research studies and clinical trials for SARS-CoV-2/COVID-19 vaccines, drugs, and other therapies.
• Resources (e.g., biorepositories, data repositories, registries, patient-reported outcomes, etc.) that can be leveraged to advance mechanistic studies of SARS-CoV-2/COVID-19 and/or PASC in women, including studies of symptoms and/or signs that specifically manifest in women of different ages and from different racial/ethnic/origin/heritage groups.
• Ways the research community can address career development needs (at any career stage) to promote research investigating sex and/or gender differences in health, resilience, and pathobiology in the response to the current pandemic and future pandemics.
• Any additional comments you would like to offer to CCRWH about the study of mechanisms of sex differences and/or the health of women in relation to SARS-CoV-2 infections/COVID-19 and/or PASC.

How to Submit a Response

The RFI is open for public comments through May 6, 2022. Comments must be received by May 6, 2022, to ensure consideration. Comments received after the public comment period has closed may be considered by the Office of Research on Women’s Health.

Submissions must be emailed to Rajeev K. Agarwal, Ph.D., Marrah Lachowicz-Scroggins, Ph.D., or Nina Schor, M.D., Ph.D., at CCRWHRFI@od.nih.go

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIH staff, and individual feedback will not be provided to any responder. The Government will use the information submitted in response to this RFI at its discretion. The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information.

Dated: March 18, 2022
Janine Austin Clayton, M.D., FARVO
Associate Director for Research on Women’s Health
Director of the Office of Research on Women’s Health
National Institutes of Health

Inquiries

Please direct all inquiries to:

Name: Rajeev K. Agarwal, Ph.D.
IC Name: Office of Research on Women's Health (ORWH)

Email: CCRWHRFI@od.nih.gov

Name: Marrah Lachowicz-Scroggins, Ph.D.
IC Name: National Heart, Lung, and Blood Institute (NHLBI)

Email: CCRWHRFI@od.nih.gov

Name: Nina Schor, M.D., Ph.D.
IC Name: National Institute of Neurological Disorders and Stroke (NINDS)

Email: CCRWHRFI@od.nih.gov