Considering Frailty in SARS-CoV-2 Vaccine Development: How Geriatricians Can Assist

Abstract

The COVID-19 pandemic has disproportionately impacted frail older adults, especially residents of long-term care (LTC) facilities. This has appropriately led to prioritization of frail older adults and LTC residents, and those who care for them, in the vaccination effort against COVID-19. Older adults have distinct immunological, clinical, and practical complexity, which can be understood through a lens of frailty. Even so, frailty has not been considered in studies of COVID-19 vaccines to date, leading to concerns that the vaccines have not been optimally tailored for and evaluated in this population even as vaccination programs are being implemented. This is an example of how vaccines are often not tested in Phase 1/2/3 clinical trials in the people most in need of protection. We argue that geriatricians, as frailty specialists, have much to contribute to the development, testing and implementation of COVID-19 vaccines in older adults. We discuss roles for geriatricians in ten stages of the vaccine development process, covering vaccine design, trial design, trial recruitment, establishment and interpretation of illness definitions, safety monitoring, consideration of relevant health measures such as frailty and function, analysis methods to account for frailty and differential vulnerability, contributions in regulatory and advisory roles, post-marketing surveillance, and program implementation and public health messaging. In presenting key recommendations pertinent to each stage, we hope to contribute to a dialogue on how to push the field of vaccinology to embrace the complexity of frailty. Making vaccines that can benefit frail older adults will benefit everyone in the fight against COVID-19.

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Keywords:

• SARS-CoV-2
• COVID-19
• vaccine
• frailty
• frail elderly
• geriatrics

Acknowledgments

KES received support from NIA P30AG028716. MKA, JEM and KR are part of the Canadian Consortium on Neurodegeneration in Aging (CCNA) Team 14, which investigates how multi-morbidity and frailty modify risk of dementia and patterns of disease expression. The CCNA receives funding from the Canadian Institutes of Health Research (CNA-137794) and partner organizations (www.ccna-ccnv.ca).

Disclosure

MKA reports grants from Sanofi, GSK, Pfizer, Canadian Frailty Network and the Public Health Agency of Canada for research on frailty in relation to vaccine preventable illness and outcomes, and honoraria from Sanofi, Pfizer and Seqirus unrelated to the present work. KES is a member of the Centers for Disease Control Advisory Committee on Immunization Practices COVID-19 vaccines work group. KR reports that he founded (as DGI Clinical) and is the Chief Science Officer of Ardea Outcomes, which has several contracts with pharma and medical device manufacturers. BC reports no conflicts. JEM reports personal fees from GSK Merck, Medicago, RestorBio, and Sanofi and travel support for scientific presentations from Sanofi and GSK, outside the submitted work; and payments to her institution from GlaxoSmithKline, Merck, Sanofi, Pfizer, Medicago, and RestorBio outside of the submitted work. The authors reported no other potential conflicts of interest for this work.