Frailty and COVID-19 mRNA Vaccine Antibody Response in the COVID-19 Community Research Partnership

Abstract

BACKGROUND COVID-19 has disproportionately affected older adults. Frailty has been associated with impaired vaccine response in other vaccine types, but the impact of frailty on mRNA vaccine response is undefined. METHODS Observational study of adults aged 55 and above from one US health care system between January 22, 2021 and September 16, 2021 with self-reported Moderna or Pfizer COVID-19 mRNA vaccine and an electronic frailty index score (eFI) from their medical record (n =1677). Participants’ frailty status was compared with positive antibody detection (seroconversion) following full vaccination and subsequent loss of positive antibody detection (seroreversion) using logistic regression models. RESULTS Of 1677 older adults with median (IQR) age, 67 (62, 72) years, and frailty status (non-frail: 879 (52%), pre-frail: 678 (40%), and frail: 120 (7.2%)), seroconversion was not detected in 23 (1.4%) over 60 days following full vaccination. Frail individuals were less likely to seroconvert than non-frail individuals, adjusted OR 3.75, 95%CI (1.04, 13.5). Seroreversion was detected in 50/1631 individuals (3.1%) over 6 months of median follow up antibody testing. Frail individuals were more likely to serorevert than non-frail individuals, adjusted OR 3.02, 95%CI (1.17, 7.33). CONCLUSIONS Overall antibody response to COVID-19 mRNA vaccination was high across age and frailty categories. While antibody detection is an incomplete descriptor of vaccine response, the high sensitivity of this antibody combined with health system data reinforce our conclusions that frailty is an independent predictor of impaired antibody response to the COVID-19 mRNA vaccines. Frailty should be considered in vaccine studies and prevention strategies.

Kinetics of COVID-19 mRNA primary and booster vaccine-associated neutralizing activity against SARS-CoV-2 variants of concern in long-term care facility residents: A prospective longitudinal study

“…Older adults with frailty have impaired vaccine effectiveness, including in uenza, varicella-zoster, and pneumococcal pneumonia vaccine (32)(33)(34). Furthermore, frailty is an independent predictor of impaired antibody responses to COVID-19 mRNA vaccines (35,36). Physical inactivity has also been shown to be a risk factor for severe COVID-19 (35,37).…”

COVID-19 mRNA Vaccine Effectiveness against Elderly Frail People

“…Recent evidence indicates that frailty can independently predict the reduced antibody response after COVID-19 mRNA vaccines in elderly people [ 1 ]. More specifically, post-vaccination reaction is weaker and even uncommon in this age group when compared with young people; and serious adverse events are more common [ 2 ].…”

Frailty and Age Impact Immune Responses to Moderna COVID-19 mRNA Vaccine

“… 18 , 21 , 52 , 53 Higher quantity antibody titers detected with ELISA are associated with protection from adverse health-related outcomes from COVID-19 and influenza, 54 – 56 but frailty and older age have been associated with waning of COVID-19 vaccine-elicited antibody. 7 , 13 , 19 , 25 , 57 However, quantitative antibody assays are incomplete descriptors of immunity to SARS-CoV-2. 58 A surrogate of protection from infection is antibody neutralization, which commonly targets the SARS-CoV-2 spike protein receptor binding domain (RBD).…”

“… 25 , 73 Furthermore, the underlying mechanisms which impact vaccine responses in frail individuals remains poorly understood. 13 , 14 Here we tested the hypothesis that frailty in older adults in a retirement community will correlate with decreased vaccine responsiveness. We assessed responses to the Moderna mRNA COVID-19 vaccine by measuring the quantity and quality of vaccine-elicited antibody, as well as vaccine-specific T cell responses.…”

“…[10][11][12] There is emerging evidence for impaired COVID-19 vaccine responses in community-dwelling frail older adults, but evaluation of immune function was limited. 13,14 While COVID-19 vaccine immune responses have been studied in the nursing home setting, [15][16][17][18] the impact of frailty on vaccine responsiveness has not been adequately assessed due to imprecise/lack of measurement of frailty, [18][19][20][21][22][23][24] homogeneous frailty status of populations, 25 or limited immunological assessments. 26 Frailty is a geriatric syndrome leading to worsened health outcomes due to impaired regulation of homeostasis, and it serves as a marker of biological aging.…”