Research and resource needs for understanding host immune responses to SARS-CoV-2 and COVID-19 vaccines during aging.

On 16 and 17 March 2021, the National Institute of Allergy and Infectious Diseases and the National Institute of Aging convened a virtual workshop to discuss developments in SARS-CoV-2 research pertaining to immune responses in older adults, COVID-19 vaccines in both aged animals and older individuals, and to gain some perspective on the critical knowledge gaps that need addressing to establish scientific priorities for future research studies.

Extending human healthspan and longevity: a symposium report.

For many years, it was believed that the aging process was inevitable and that age-related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age-related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life. Experts in the field have made remarkable advancements in understanding the mechanisms underlying biological aging and identified ways to target aging pathways using both novel agents and repurposed therapies. While geroscience researchers currently face significant barriers in bringing therapies through clinical development, proof-of-concept studies, as well as early-stage clinical trials, are underway to assess the feasibility of drug evaluation and lay a regulatory foundation for future FDA approvals in the future.

Challenges with Conducting an Investigational Drug Study in Older Adults in Nursing Homes During a Pandemic

In the early months of the pandemic, SARS-CoV-2 infected nursing home residents in explosive and deadly outbreaks. Nursing home residents disproportionately accounted for over 40% of COVID-19 mortality nationally. This national emergency drove scientific and public health experts to develop and implement administrative, clinical, and research programs to limit the pandemic’s impact, especially for high-risk individuals, such as those hospitalized or living in nursing homes. Nursing home policies, prompted by the Centers for Medicare & Medicaid Services (CMS) and the Centers for Disease Control and Prevention (CDC) guidance, severely restricted access beginning in March 2020 in an effort to limit disease exposure. In July 2020 we began the process to conduct an investigational SARS-CoV-2 post exposure prophylaxis study of nursing home residents, incorporating FDA guidance developed for conducting investigational drug trials in the context of COVID-19. Our research teams adapted our nursing home engagement, resident consenting and research data collection strategies accordingly. We remotely screened residents living in any of 28 nursing homes for eligibility to participate, ultimately consenting and randomizing individuals in 11 facilities. Of the 2,683 nursing home residents 65 years or older we screened, 48 (1.8%) agreed to consent individually or through proxy, most often a legally authorized representative. We will describe our research methods, with emphasis on how we addressed challenges presented due to performing all research tasks remotely and identify strategies that can qualitatively improve the remote nursing home research experience.

Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era.

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.