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Anti-SARS-CoV-2 antibody levels and kinetics of vaccine response: potential role for unresolved inflammation following recovery from SARS-CoV-2 infection.

ABSTRACT: The immune response after SARS-CoV-2 vaccine administration appears to be characterized by high inter-individual variation, even in SARS-CoV-2 positive subjects, who could have experienced different post-infection, unresolved conditions. We monitored anti-SARS-CoV-2 IgG levels and kinetics along with circulating biomarkers in a cohort of 175 healthcare workers during early immunization with COVID-19 mRNA-LNP BNT162b2 vaccine, to identify the associated factors. Subjects with a previous SARS-CoV-2 infection were characterized by higher BMI and CRP levels and lower neutrophil count with respect to naïve subjects. Baseline IgG levels resulted associated with CRP independently on BMI and inflammatory diseases. Among 137 subjects undergoing vaccination and monitored after the first and the second dose, three kinetic patterns were identified. The pattern showing a rapid growth was characterized by higher IgG levels at baseline and higher CRP and MCHC levels than negative subjects. Subjects previously exposed to SARS-CoV-2 showed higher levels of CRP, suggesting persistence of unresolved inflammation. These levels are the main determinant of IgG levels at baseline and characterized subjects belonging to the best performing, post-vaccine antibody kinetic pattern.

SUBMITTER: Gianfagna F

PROVIDER: S-EPMC8749002 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe antibody response after vaccination is impaired in common variable immunodeficiency (CVID).ObjectiveWe aimed to study the spike receptor-binding domain IgG antibody (anti-S-RBD) levels during a four-dose SARS-CoV-2 vaccination strategy and after monoclonal antibody (mAB) treatment in CVID. Moreover, we assessed the anti-S-RBD levels in immunoglobulin replacement therapy (IgRT) products.MethodsIn an observational study, we examined anti-S-RBD levels after the second, third, and fourth dose of mRNA SARS-CoV-2 vaccines. Moreover, we measured anti-S-RBD after treatment with mAB. Finally, anti-S-RBD was assessed in common IgRT products. Antibody non-responders (anti-S-RBD < 7.1) were compared by McNemar's test and anti-S-RBD levels were compared with paired and non-paired Wilcoxon signed rank tests as well as Kruskal-Wallis tests.ResultsAmong 33 individuals with CVID, anti-S-RBD levels increased after the third vaccine dose (165 BAU/ml [95% confidence interval: 85; 2280 BAU/ml], p = 0.006) and tended to increase after the fourth dose (193 BAU/ml, [-22; 569 BAU/ml], p = 0.080) compared to the previous dose. With increasing number of vaccinations, the proportion of patients who seroconverted (anti-S-RBD ≥ 7.1) increased non-significantly. mAB treatment resulted in a large increase in anti-S-RBD and a higher median level than gained after the fourth dose of vaccine (p = 0.009). IgRT products had varying concentrations of anti-S-RBD (p < 0.001), but none of the products seemed to affect the overall antibody levels (p = 0.460).ConclusionMultiple SARS-CoV-2 vaccine doses in CVID seem to provide additional protection, as antibody levels increased after the third and fourth vaccine dose. However, anti-S-RBD levels from mAB outperform the levels mounted after vaccination.Clinical implicationsBoosting with SARS-CoV-2 vaccines seems to improve the antibody response in CVID patients.Capsule summaryThe third and possibly also the fourth dose of mRNA SARS-CoV-2 vaccine in CVID improve the antibody response as well as stimulate seroconversion in most non-responders.

Project description:ImportanceThe factors associated with long-term serum levels of anti-SARS-CoV-2 antibodies after COVID-19 vaccination in healthy individuals have rarely been investigated.ObjectiveTo investigate factors associated with anti-SARS-CoV-2 antibody levels.Design, setting, and participantsThis prospective cohort study included health care workers at Kyungpook National University Chilgok Hospital (Daegu, Korea) with no history of SARS-CoV-2 infection who received 2 doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech; first dose, March 17-20, 2021; second dose, April 7-10, 2021). Serum samples were collected at 2, 4, and 6 months after the second injection.InterventionsSARS-CoV-2 BNT162b2 mRNA vaccine.Main outcomes and measuresAnti-SARS-CoV-2 specific antibodies were measured using enzyme-linked immunosorbent assay kits up to 6 months after the receipt of 2 doses of the BNT162b2 mRNA COVID-19 vaccine. The main outcome was factors associated with anti-SARS-CoV-2 antibody levels at 6 months.ResultsAll 50 participants (mean [SD] age, 34.7 [9.4] years; 10 [20.0%] male; mean [SD] body mass index, 21.8 [5.4]) acquired anti-SARS-CoV-2 antibodies and maintained positive antibody (cutoff ≥30%) up to 6 months. The mean serum antibody level decreased with time (91.9%, 89.3%, and 81.5% at 2, 4, and 6 months, respectively). Serum antibody levels at 6 months were correlated with antibody levels at 2 months (R = 0.944; P < .001). The anti-SARS-CoV-2-specific antibody level was inversely correlated with weight, body mass index, body fat amount, and body weight to height ratio in Spearman correlation analysis. A 1-SD increase in body weight, weight to height ratio, and body mass index was associated with a 4%- to 5%-decrease in anti-SARS-CoV-2 antibodies in multiple linear regression analysis for women. In multivariate analysis for categorized variables, lower serum level of antibody (ie, <81.5%) was associated with weight (weight ≥55 kg: odds ratio, 9.01; 95% CI, 1.44-56.40). The probabilities of less than 70% and less than 80% antibody at 6 months were 0% and 11% in participants weighing less than 55 kg, respectively, but 16% and 42% in participants weighing 55 kg or greater.Conclusions and relevanceIn this study, the inverse correlation of anti-SARS-CoV-2-specific antibody levels with weight was sustained up to 6 months after vaccination. A booster shot of BNT162b2 mRNA vaccination may be given later than 6 months after the second dose in young and middle-aged healthy persons with low body weight.

Project description:ObjectivesThe recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown.MethodsThis was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination.ResultsOf the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti-SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1-69) to 243 (IQR, 2-4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25-184.5) to 1824 (IQR, 161-9686)), followed by the rheumatology (from 22 (IQR, 1-106) to 1291 (IQR, 6-6231)) and haemato-oncology (from 1 (IQR, 0.1-7) to 7.5 (IQR, 0.1-407.5)) cohorts. The χ2 test was 8.30 for difference in fold change (p = 0.016). Of the 193 patients who were seronegative at baseline, 76 became seropositive after vaccination, corresponding to a 39.4% (95% CI, 32.8%-46.4%) seroconversion rate. Transplant patients had the highest seroconversion rate (58.3% (95% CI, 44.3%-71.2%)), followed by rheumatology (44.1% (95% CI, 28.9%-60.5%)) and haemato-oncology (29.7% (95% CI, 22%-38.8%); χ2 = 11.87; p = 0.003) patients.DiscussionA third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.

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Anti-SARS-CoV-2 antibody levels and kinetics of vaccine response: potential role for unresolved inflammation following recovery from SARS-CoV-2 infection.

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