COVID-19 after BNT162b2 two-dose primary series does not improve the efficacy of a booster dose in nursing home residents.
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ABSTRACT:
SUBMITTER: Blain H
PROVIDER: S-EPMC10033849 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
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COVID-19 after BNT162b2 two-dose primary series does not improve the efficacy of a booster dose in nursing home residents.
Blain Hubert H Tuaillon Edouard E Gamon Lucie L Pisoni Amandine A Aouinti Safa S Picot Marie-Christine MC Bousquet Jean J
Clinical and translational allergy 20230301 3
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Project description:BackgroundInfection control during COVID-19 outbreaks in nursing facilities is a critical public health issue. Antibody responses before and after the third (booster) dose of SARS-CoV-2 vaccination in nursing home residents have not been fully characterized.MethodsThis study included 117 individuals: 54 nursing home residents (mean age, 83.8 years; 39 SARS-CoV-2-naive and 15 previously infected) and 63 healthcare workers (mean age, 45.8 years; 32 SARS-CoV-2-naive and 31 previously infected). Anti-spike (receptor-binding domain [RBD]) and anti-nucleocapsid antibody responses to BNT162b2 mRNA vaccination and their related factors were evaluated using pre- (shortly and 6 months after the second dose) and post-booster vaccination samples.ResultsThe median anti-spike (RBD) IgG level in SARS-CoV-2-naive residents 6 months after the second dose was the lowest among the four groups, with a decreasing rate of over 90%. The median rate of increase before and after the third dose in SARS-CoV-2-naive residents was significantly higher than that in SARS-CoV-2-naive healthcare workers (64.1- vs. 37.0-fold, P = 0.003), with the highest level among the groups. The IgG ratio of SARS-CoV-2-naive residents to healthcare workers after the second and third doses changed from one-fifth (20%) to one-half (50%). The rate of increase after the third dose in previously infected individuals was three- to fourfold, regardless of residents or healthcare workers.ConclusionsAdvanced aged nursing home residents, poor responders in the initial SARS-CoV-2 vaccine series, could obtain sufficient antibody responses with the additional booster dose, despite more than 6 months after the second.
| S-EPMC9530588 | biostudies-literature
Project description:Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8 months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.
| S-EPMC11493945 | biostudies-literature
Project description:BackgroundAs older age and having certain comorbidities can influence humoral responses to vaccination, we studied antibody responses after the COVID-19 booster campaigns in nursing home (NH) residents.MethodsIn a two year longitudinal study with Dutch NH residents (n = 107), aged 50 years and over, we monitored antibody responses in serum prior to and after vaccination with a third, fourth BNT162b2 (wild-type; WT), and a BNT162b2 bivalent (WT/OMI BA.1) fifth vaccine. Data on vaccinations, infections, comorbidities, and, for some participants, clinical symptoms after infection were obtained with questionnaires. Data were compared to antibody responses of BNT162b2-vaccinated, healthier community-dwelling older adults (n = 32) from the general population.ResultsThe booster vaccinations substantially increased anti-WT and anti-Omicron SARS-CoV-2 Spike S1 (S1) and Spike protein receptor binding domain (RBD)-antibody concentrations of NH residents. This resulted in comparable antibody levels between NH residents and healthier community-dwelling older adults and between infection-naïve and infected NH residents, and in a decline in treatment duration and clinical symptom severity in SARS-CoV-2-infected NH residents. Between one and twelve months after the bivalent fifth dose, anti-Omicron BA.1 antibody levels of the NH residents waned faster than those against the WT strain.ConclusionsThe booster vaccinations upheld humoral responses of NH residents to WT and Omicron SARS-CoV-2. This, in addition to the less virulent circulating strains, decreased symptom severity and treatment durations for SARS-CoV-2-infected NH residents. Boosting this vulnerable group should, therefore, be continued to prevent waning of humoral immunity and achieve sufficient protection especially against newly emerging variants of concern.
| S-EPMC11694371 | biostudies-literature
Project description:BackgroundNursing home (NH) residents have borne a disproportionate share of SARS-CoV-2 morbidity and mortality. Vaccines have limited hospitalisation and death from earlier variants in this vulnerable population. With the rise of Omicron and future variants, it is vital to sustain and broaden vaccine-induced protection. We examined the effect of boosting with BNT162b2 mRNA vaccine on humoral immunity and Omicron-specific neutralising activity among NH residents and healthcare workers (HCWs).MethodsWe longitudinally enrolled 85 NH residents (median age 77) and 48 HCWs (median age 51), and sampled them after the initial vaccination series; and just before and 2 weeks after booster vaccination. Anti-spike, anti-receptor binding domain (RBD) and neutralisation titres to the original Wuhan strain and neutralisation to the Omicron strain were obtained.FindingsBooster vaccination significantly increased vaccine-specific anti-spike, anti-RBD, and neutralisation levels above the pre-booster levels in NH residents and HCWs, both in those with and without prior SARS-CoV-2 infection. Omicron-specific neutralisation activity was low after the initial 2 dose series with only 28% of NH residents' and 28% HCWs' titres above the assay's lower limit of detection. Omicron neutralising activity following the booster lifted 86% of NH residents and 93% of HCWs to the detectable range.InterpretationWith boosting, the vast majority of HCWs and NH residents developed detectable Omicron-specific neutralising activity. These data provide immunologic evidence that strongly supports booster vaccination to broaden neutralising activity and counter waning immunity in the hope it will better protect this vulnerable, high-risk population against the Omicron variant.FundingNIH AI129709-03S1, U01 CA260539-01, CDC 200-2016-91773, and VA BX005507-01.
| S-EPMC9122310 | biostudies-literature
Project description:BackgroundWe sought to compare rates of adverse events among nursing home residents who received an mRNA COVID-19 vaccine booster dose with those who had not yet received their booster.MethodsWe assessed a prospective cohort of 11,200 nursing home residents who received a primary COVID-19 mRNA vaccine series at least 6 months prior to September 22, 2021 and received a third "booster dose" between September 22, 2021 and February 2, 2022. Residents lived in 239 nursing homes operated by Genesis HealthCare, spanning 21 U.S. states. We screened electronic health records for 20 serious vaccine-related adverse events that are monitored following receipt of COVID-19 vaccination by the CDC's Vaccine Safety Datalink. We matched boosted and yet-to-be boosted residents during the same time period, comparing rates of events occurring 14 days after booster administration with those occurring 14 days prior to booster administration. To supplement previously reported background rates of adverse events, we report background rates of medical conditions among nursing home residents during 2020, before COVID-19 vaccines were administered in nursing homes. Events occurring in 2021-2022 were confirmed by physician chart review. We report unadjusted rates of adverse events and used a false discovery rate procedure to adjust for multiplicity of events tested.ResultsNo adverse events were reported during the 14 days post-booster. A few adverse events occurred prior to booster (ischemic stroke: 49.4 per 100,000 residents, 95% CI: 21.2, 115.7; venous thromboembolism: 9.9 per 100,000 residents, 95% CI: 1.7, 56.0), though differences in event rates pre- versus post-booster were not statistically significant (p < 0.05) after adjusting for multiple comparisons. No significant differences were detected between post-booster vaccination rates and prior year 14-day background rates of medical conditions.ConclusionsNo safety signals were detected following a COVID-19 mRNA vaccine booster dose in this large multi-state sample of nursing home residents.
| S-EPMC9115078 | biostudies-literature
Project description:BackgroundThe protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised.MethodsIn a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 residents who had received a two-dose regimen of mRNA vaccine and a booster dose of Pfizer BNT162b2 vaccine. We excluded individuals that did not receive three vaccine doses or did not have available sera samples. We measured anti-S IgG antibodies and neutralisation capacity in sera taken 56 (28-68) and 55 (48-64) days (median (range)) after the 2nd and 3rd vaccine doses, respectively. Antibodies targeting the SARS-CoV-2 Spike protein were measured with the S-Flow assay as binding antibody units per milliliter (BAU/mL). Neutralising activities in sera were measured as effective dilution 50% (ED50) with the S-Fuse assay using authentic isolates of delta and omicron BA.1.FindingsAmong the 38 elderly individuals recruited to the cohort study between November 23rd, 2020 and April 29th, 2021, with median age of 88 (range 72-101) years, 30 (78.95%) had been previously infected with SARS-CoV-2. After three vaccine doses, serum neutralising activity was lower against omicron BA.1 (median ED50 of 774.5, range 15.0-34660.0) than the delta variant (median ED50 of 4972.0, range 213.7-66340.0), and higher among previously infected (ie, convalescent; median ED50 against omicron: 1088.0, range 32.6-34660.0) compared with infection-naive residents (median ED50 against omicron: 188.4, range 15.0-8918.0). During the French omicron wave in December 2021-January 2022, 75% (6/8) of naive residents were infected, compared to 25% (7/30) of convalescent residents (P=0.0114). Anti-Spike antibody levels and neutralising activity against omicron BA.1 after a third BNT162b2 booster dose were lower in those with breakthrough BA.1 infection (n=13) compared with those without (n=25), with a median of 1429.9 (range 670.9-3818.3) BAU/mL vs 2528.3 (range 695.4-8832.0) BAU/mL (P=0.029) and a median ED50 of 281.1 (range 15.0-2136.0) vs 1376.0 (range 32.6-34660.0) (P=0.0013), respectively.InterpretationThis study shows that elderly individuals who received three vaccine doses elicit neutralising antibodies against the omicron BA.1 variant of SARS-CoV-2. Elderly individuals who had also been previously infected showed higher neutralising activity compared with naive individuals. Yet, breakthrough infections with omicron occurred. Individuals with breakthrough infections had significantly lower neutralising titers compared to individuals without breakthrough infection. Thus, a fourth dose of vaccine may be useful in the elderly population to increase the level of neutralising antibodies and compensate for waning immunity.FundingInstitut Pasteur, Fondation pour la Recherche Médicale (FRM), European Health Emergency Preparedness and Response Authority (HERA), Agence nationale de recherches sur le sida et les hépatites virales - Maladies Infectieuses Emergentes (ANRS-MIE), Agence nationale de la recherche (ANR), Assistance Publique des Hôpitaux de Paris (AP-HP) and Fondation de France.
| S-EPMC9307278 | biostudies-literature
Project description:Interventions to improve the fracture prevention in nursing homes are needed.Cluster-randomized, single-blind, controlled trial of a multi-modal quality improvement intervention. Nursing homes (n=67) with > or =10 residents with a diagnosis of osteoporosis or recent hip fracture (n=606) were randomized to receive an early or delayed intervention consisting of audit and feedback, educational modules, teleconferences, and academic detailing. Medical record abstraction and the Minimum Data Set were used to measure the prescription of osteoporosis therapies before and after the intervention period. Analysis was at the facility-level and Generalized Estimating Equation modeling was used to account for clustering.No significant improvements were observed in any of the quality indicators. The use of osteoporosis pharmacotherapy or hip protectors improved by 8.0% in the intervention group and 0.6% in the control group, but the difference was not statistically significant (P=.72). Participation in the intervention activities was low, but completion of the educational module (odds ratio [OR] 4.8, 95% confidence interval [CI], 1.9-12.0) and direct physician contact by an academic detailer (OR 4.5, 95% CI, 1.1-18.2) were significantly associated with prescription of osteoporosis pharmacotherapy or hip protectors in multivariable models.Audit-feedback and education interventions were ineffective in improving fracture prevention in the nursing home setting, although results may have been tempered by low participation in the intervention activities.
| S-EPMC2288656 | biostudies-literature
Project description:BackgroundBefore the omicron era, health care workers were usually vaccinated with either the primary 2-dose ChAdOx1 nCoV-19 (Oxford-AstraZeneca) series plus a booster dose of BNT162b2 (Pfizer-BioNTech) (CCB group) or the primary 2-dose BNT162b2 series plus a booster dose of BNT162b2 (BBB group) in Korea.MethodsThe two groups were compared using quantification of the surrogate virus neutralization test for wild type severe acute respiratory syndrome coronavirus 2 (SVNT-WT), the omicron variant (SVNT-O), spike-specific IgG, and interferon-gamma (IFN-γ), as well as the omicron breakthrough infection cases.ResultsThere were 113 participants enrolled in the CCB group and 51 enrolled in the BBB group. Before and after booster vaccination, the median SVNT-WT and SVNT-O values were lower in the CCB (SVNT-WT [before-after]: 72.02-97.61%, SVNT-O: 15.18-42.29%) group than in the BBB group (SVNT-WT: 89.19-98.11%, SVNT-O: 23.58-68.56%; all P < 0.001). Although the median IgG concentrations were different between the CCB and BBB groups after the primary series (2.677 vs. 4.700 AU/mL, respectively, P < 0.001), they were not different between the two groups after the booster vaccination (7.246 vs. 7.979 AU/mL, respectively, P = 0.108). In addition, the median IFN-γ concentration was higher in the BBB group than in the CCB group (550.5 and 387.5 mIU/mL, respectively, P = 0.014). There was also a difference in the cumulative incidence curves over time (CCB group 50.0% vs. BBB group 41.8%; P = 0.045), indicating that breakthrough infection occurred faster in the CCB group.ConclusionThe cellular and humoral immune responses were low in the CCB group so that the breakthrough infection occurred faster in the CCB group than in the BBB group.
| S-EPMC10202617 | biostudies-literature
Project description:BackgroundData suggest that antibody responses following COVID-19 vaccines are a correlate of protection. Some studies, including the clinical trials of COVID-19 mRNA vaccines, did not stratify and evaluate whether antibody responses to COVID-19 vaccines differed between the sexes or with aging. This gap in research is particularly relevant for older populations such as nursing home residents (NHR). We hypothesized that sex differences in vaccine-induced antibody responses may intersect with age and be diminished among older adults residing in nursing homes.MethodsWe analyzed serum samples from 638 NHRs collected serially after the primary two-dose series and three subsequent booster doses of mRNA SARS-CoV-2 vaccinations. We analyzed anti-Spike IgG and neutralizing antibody titers to the Wuhan and Omicron BA.4/5 variant strains. Mixed-effects models predicting log-transformed titers were estimated to compare responses across vaccine doses, focusing on sex-differential responses. For detected post-dose sex differences, additional sample times were analyzed to assess the duration of the difference.ResultsFollowing the primary series, female NHRs with a prior history of SARS-CoV-2 infection had significantly higher Wuhan anti-Spike antibodies and neutralizing antibody titers than male NHRs with differences persisting up to nine months post-vaccination. Subsequent monovalent booster doses and a bivalent booster dose eliminated this disparity. We did not detect any differential response to the Omicron BA.4/5 variant.ConclusionsThe blunting of sex differences in antibody response observed following the primary series by the 1st booster dose underscores the importance of booster vaccination in this population.
| S-EPMC11889018 | biostudies-literature
Project description:Primary series vaccination with BNT162b2 followed by a booster 5 months later has been recommended for healthy adolescents. We aimed to describe the immunogenicity in a fractional dose of BNT162b2. Adolescents aged 12-18 years were randomized into six arms for primary series administration: 3wPZ30/30 (reference group), 3wPZ30/20, 3wPZ20/20, 6wPZ30/30, 6wPZ30/20, and 6wPZ20/20 μg. A booster was given at 5 months after the second dose using either 10 or 15 μg of BNT162b2. Immunogenicity following vaccination was determined by IgG against receptor-binding domain (anti-S-RBD IgG; BAU/mL), surrogate virus neutralization test (sVNT; %inhibition) and pseudovirus neutralization (pVNT;ID50) against Omicron. Non-inferiority criteria were defined as a lower boundary of the geometric mean ratio (GMR) being greater than 0.67. From September to October 2021, 118 adolescents with a median age (IQR) of 14.9 years (13.9-16.7) were enrolled. Fourteen days after the primary series, the geometric means (GMs) of anti-S-RBD IgG (BAU/mL) were 3090 (95% CI 2761-3460) in 3wPZ30/30. The GMRs of anti-S-RBD were: 0.80 (95% CI 0.67-0.97) in 3wPZ30/20; 1.00 (95% CI 0.83-1.20) in 3wPZ20/20; 1.37 (95% CI 1.13-1.65) in 6wPZ30/30; 1.24 (95% CI 1.02-1.50) in 6wPZ30/20; and 1.36 (1.13-1.64) in 6wPZ20/20. After a booster dose with 15 μg (n = 24) of BNT162b2, sVNT and pVNT against Omicron variant were 91.6 (95% CI 88.4-94.9) and 331 (95% CI 221-495), respectively. In the group that received 10 μg of BNT162b2 (n = 25), sVNT was 85.6 (95% CI 80.0-91.6) and pVNT was 397 (95% CI 267-590). Healthy adolescents had good immune responses to the fractional dose regimen of BNT162b2 and this may be considered as an alternative option.
| S-EPMC9609361 | biostudies-literature