Previous SARS-CoV-2 Infection, Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents

Dyer, Adam H.; Noonan, Claire; McElheron, Matt; Batten, Isabella; Reddy, Conor; Connolly, Emma; Pierpoint, R; Murray, Caroline; Leonard, Alan G.; C, Higgins; Reilly, Phyllis; Boran, Gerard; Phelan, Thomas; McCormack, William; O’Neill, Desmond; Fallon, Aoife; Brady, Gareth; O’Farrelly, Cliona; Bourke, Nollaig M.; Kennelly, Seán

doi:10.1016/j.jamda.2021.12.001

Cited by 28 publications

(22 citation statements)

References 26 publications

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“…A pool of serum from 27 PCRpositive healthcare workers from IMM was used for assay calibration. In a study of vaccine-induced immune responses, 86 residents of nursing homes in Dublin, Ireland, were followed before and after receiving two doses of the Pfizer BNT162b2 vaccine [21]. Samples were collected at baseline and 5 weeks and 6 months after the second dose.…”

Section: Samplesmentioning

confidence: 99%

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

García

Woudenberg

Rosado

et al. 2022

Viruses

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Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics.

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Section: Samplesmentioning

confidence: 99%

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

García

Woudenberg

Rosado

et al. 2022

Viruses

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“…Therefore, we concluded that the only variable that showed an association with having more severe adverse reactions was the existence of a previous positive serology. Having had a previous COVID-19 infection was the strongest predictor of anti-spike antibody titers at 3 and 6 months [ 21 ] and this would justify the higher frequency of severe reactions observed in our sample, compared with the results obtained in other studies [ 22 ].…”

Section: Discussionmentioning

confidence: 65%

“…It has to be mentioned that our nursing home under study was in the upper range of SARS-CoV-2 infection during the first pandemic wave [ 23 , 24 ]. In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months [ 21 ]. The persistence of IgG after vaccination in nursing home residents is high (95.2%) and was similar to the rate found in our study [ 16 ], regardless of the degree of frailty [ 25 ].…”

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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“…Reliable measures of frailty including the CFS and have been described in a limited number of COVID-19 vaccine studies in the nursing home setting. 25 , 26 , 57 A single-site nursing home study in France had little variability in frailty status, which limited their ability to detect the association of frailty with antibody and cellular responses. 25 Interestingly, a study from Poland with mixed frailty status of participants described little effect of frailty on antibody responses to the Pfizer mRNA vaccine, though their measurements did not include assessment past 2-weeks post second vaccine dose.…”

Section: Discussionmentioning

confidence: 99%

“… 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).…”

Section: Introductionmentioning

confidence: 99%

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

Semelka

DeWitt

Blevins

et al. 2022

Preprint

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BACKGROUND: Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses.METHODS: We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used antibody titers in linear mixed-effects linear regression with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used clinical predictors and cellular phenotype variables in linear regression models.RESULTS: Participants (n=15) had median age of 90 years and mild, moderate, or severe frailty scores (n=3, 7, or 5 respectively). After 2 vaccine doses, anti-spike antibody titers were higher in 5-fold higher in individuals with mild frailty compared to severe frailty and 9-fold higher in individuals with prior COVID-19 infection compared to uninfected (p=0.02 and p<0.001). Following the booster, titers improved regardless of COVID-19 infection or frailty. Antibody avidity significantly declined following 2 vaccine doses regardless of frailty status, but reached maximal avidity after the booster. Spike-specific CD4+ T cell responses were modulated by frailty and terminally differentiated effector memory TEMRA cells, and spike-specific TFH cell responses were inversely correlated with age. Additionally, an immune-senescent memory T cell phenotype was correlated with frailty and functional decline.CONCLUSIONS: We described the separate influences of frailty and age on adaptive immune responses to the Moderna COVID-19 mRNA vaccine. Though overall antibody responses were robust, higher frailty diminished initial antibody quantity, and all older adults had impaired antibody avidity. Following the booster, antibody responses improved, overcoming the effects of age and frailty. CD4+ T cell responses were independently impacted by age, frailty, and burden of immune-senescence. Frailty was correlated with increased burden of immune-senescence, suggesting an immune-mediated mechanism for physiological decline.

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Previous SARS-CoV-2 Infection, Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents

Cited by 28 publications

References 26 publications

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

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

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

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