Immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in older residents of a long-term care facility: relation with age, frailty and prior infection status

Seiffert, Piotr; Konka, Adam; Kasperczyk, Janusz; Kawa, Jacek; Lejawa, Mateusz; Maślanka-Seiffert, Barbara; Zembala-John, Joanna; Bugdol, Monika; Romanik, Małgorzata; Bułdak, Rafał Jakub; Marcisz, Czesław; Derejczyk, Jarosław; Religa, Dorota

doi:10.1007/s10522-021-09944-9

Cited by 22 publications

(18 citation statements)

References 53 publications

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“…The impact of frailty on COVID-19 vaccine outcomes has only been investigated without consideration of sex. Frailty does not impact vaccine-induced antibody responses against BNT162b2 when controlling for sex and other covariates ( Ríos et al, 2021 ) or when ignoring sex ( Demaret et al, 2021 ; Seiffert et al, 2021 ). Frailty does, however, increase the risk of post-vaccination infection when controlling for sex and age ( Antonelli et al, 2021 ; Hollinghurst et al, 2021 ).…”

Section: Introductionmentioning

confidence: 96%

Roadmap for Sex-Responsive Influenza and COVID-19 Vaccine Research in Older Adults

et al. 2022

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Sex differences in the immune system are dynamic throughout the lifespan and contribute to heterogeneity in the risk of infectious diseases and the response to vaccination in older adults. The importance of the intersection between sex and age in immunity to viral respiratory diseases is clearly demonstrated by the increased prevalence and severity of influenza and COVID-19 in older males compared to older females. Despite sex and age biases in the epidemiology and clinical manifestations of disease, these host factors are often ignored in vaccine research. Here, we review sex differences in the immunogenicity, effectiveness, and safety of the influenza and COVID-19 vaccines in older adults and the impact of sex-specific effects of age-related factors, including chronological age, frailty, and the presence of comorbidities. While a female bias in immunity to influenza vaccines has been consistently reported, understanding of sex differences in the response to COVID-19 vaccines in older adults is incomplete due to small sample sizes and failure to disaggregate clinical trial data by both sex and age. For both vaccines, a major gap in the literature is apparent, whereby very few studies investigate sex-specific effects of aging, frailty, or multimorbidity. By providing a roadmap for sex-responsive vaccine research, beyond influenza and COVID-19, we can leverage the heterogeneity in immunity among older adults to provide better protection against vaccine-preventable diseases.

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Section: Introductionmentioning

confidence: 96%

Roadmap for Sex-Responsive Influenza and COVID-19 Vaccine Research in Older Adults

et al. 2022

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“…Furthermore, studies investigating frailty have not found an effect on antibody responses [34][35][36], but have reported that frailty increases the risk of post-vaccination breakthrough infection [37,38], suggesting that the immunogenicity studies may have been under-powered to observe an effect of frailty or that lack of consideration of biological sex obscured the effect.…”

Section: Discussionmentioning

confidence: 99%

Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

Shapiro

Park

Aytenfisu

et al. 2022

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Background: Male sex and old age are risk factors for severe COVID-19, but the intersection of sex and aging on antibody responses to SARS-CoV-2 vaccines has not been characterized. Methods: Plasma samples were collected from older adults (75-98 years) before and after three doses of SARS-CoV-2 mRNA vaccination, and from younger adults (18-74 years) post-dose two, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S-receptor binding domain [S-RBD], and nucleocapsid [N]) and functional activity against S were measured against the vaccine virus and variants of concern (VOC). Results: Vaccination induced greater antibody titers in older females than males, with both age and frailty associated with reduced antibody responses to vaccine antigens in males, but not females. ACE2 binding inhibition declined more than anti-S or anti-S-RBD IgG in the six months following the second dose (28-fold vs. 12- and 11-fold decreases in titer). The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOC were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOC than females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with disparities being greater in males than females. Conclusion: Older and frail males may be more vulnerable to breakthrough infections due to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

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“…With antibody quantification, various studies verified that although the antibodies are present, there is a decrease in these antibodies. Pre-vaccination COVID-19 illness was the only factor associated with a lower rate of antibody decline at 6 months, while frailty, disability, older age, cognitive impairment, or comorbidity were not associated with the extent of antibody loss [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Safety, Effectiveness, and Immunogenicity 6 Months After BNT162B2 mRNA Vaccine in Frail Nursing Home Residents

et al. 2022

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Background Elderly people who reside in long-term care facilities form a frail and vulnerable population, with multiple pathologies and high percentages of cognitive and functional disability. Objectives The aims of this study were to assess the safety of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in frail nursing home residents and to evaluate its effectiveness 6 months after full vaccination. Design This was an ambispective observational study. Setting Residents of a long-term care facility in Madrid, Spain. Participants One hundred and thirty-seven nursing home residents (81.8% female, mean age 87.77 ± 8.31 years) with high comorbidity (61.3% Charlson Index ≥ 3) and frailty (75% Clinical Frail Scale ≥ 7) who received the BNT162B2 mRNA vaccine. Measurements Safety data were collected to evaluate the type of adverse drug reactions and their duration, severity, and causality. Immunogenicity was tested 6 months after the primary vaccination and effectiveness was evaluated by the incidence of SARS-CoV-2 infection, the number of hospital admissions, and mortality due to coronavirus disease 2019 (COVID-19). Results Safety: Of the residents, 21.9% had some adverse reaction and 5.8% had a severe or more serious adverse reaction. The most frequent adverse reactions were fatigue (13.1%), pyrexia (12.4%), and headache (7.3%). No association was observed between frailty (including a need for palliative care) and clinical, functional or cognitive status of the participants and the occurrence of adverse events. Immunogenicity and Effectiveness : After 6 months of vaccination, only one case of SARS-CoV-2 infection was confirmed in the vaccinated residents. Most of the nursing home residents presented positive serology (95.2%). Loss of immunogenicity was associated with older age (95.12 ± 3.97 vs. 87.24 ± 8.25 years; p = 0.03) and no previous COVID-19 infection (16.6% vs. 70%; p < 0.001). Binary logistic regression models did not reveal this association. Conclusion The BNT162B2 vaccine is well tolerated and effective in nursing home residents, independently of their clinical, functional, cognitive, or frailty characteristics. For the most part, immunogenicity has been maintained over time, regardless of comorbidity, functional status or frailty.

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Immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in older residents of a long-term care facility: relation with age, frailty and prior infection status

Cited by 22 publications

References 53 publications

Roadmap for Sex-Responsive Influenza and COVID-19 Vaccine Research in Older Adults

Roadmap for Sex-Responsive Influenza and COVID-19 Vaccine Research in Older Adults

Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

Safety, Effectiveness, and Immunogenicity 6 Months After BNT162B2 mRNA Vaccine in Frail Nursing Home Residents

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