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1.
Respir Res ; 23, 2022.
Article in English | PMC | ID: covidwho-2009401

ABSTRACT

Background: Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy. Methods: We conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4–6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021. Results: All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207–811] AU/ml vs. 820.75 [IQR, 459–1313] AU/ml;P < 0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P < 0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [IQR, 4.25–165] AU/ml vs. 970.1 [IQR, 505–1926] AU/ml;P < 0.001). Conclusion: IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, and maintain a 100% seropositivity rate 4–6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD treated with anti-inflammatory therapy, 48% were seronegative 4–6 months after the second vaccine dose. Moreover, treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments. Supplementary Information: The online version contains supplementary material available at 10.1186/s12931-022-02155-x.

3.
Journal of Crohn's and Colitis ; 16:i337-i338, 2022.
Article in English | EMBASE | ID: covidwho-1722324

ABSTRACT

Background: While vaccines against COVID-19 are effective in healthy individuals, we reported significantly lower serologic responses to BNT162b2 in patients with inflammatory bowel diseases (IBD) treated with anti-tumor necrosis factor (TNF) α agents. As this was apparent already, 4 weeks post vaccination, vaccine longevity is concerning. Aim: to assess long-term serologic responses to BNT162b2 in patients with IBD stratified according to medical treatment. Methods: A prospective, observational multi-center Israeli study. Patients with IBD (anti-TNFα treated versus non-anti-TNFα treated) and healthy controls (HC) were followed from before the, 1st BNT162b2 dose until, 6 months after vaccination. COVID-19 spike (S) and nucleocapsid (N) antibodies (Abs) concentrations were analyzed by ELISA, followed by neutralization studies. Specific anti-receptor binding domain (RBD) memory B-cells response, serologic responses against variants of concern (VOCs), Beta, Gamma and Delta, immunoglobulin levels and lymphocyte cell subsets were evaluated as well. Safety was assessed using questionnaires, clinical and laboratory data. Results: Of, 193 subjects, 130 had IBD (45 and, 85 in the anti-TNFα and non-anti-TNFα groups, respectively), 63 HC. Serologic response assessed, 176 (median) days (IQR, 166-186) and compared to, 4 weeks after, 1st dose significantly declined in all three groups, but was lowest in the anti- TNFα group:, 6 months anti-S Abs titer geometric means:, 193 (95%CI:, 128-292), 703 (520-951), and, 1253 (1023-1534) in anti-TNFα, nonanti- TNFα and HC groups, respectively, p<0.001, Figure, 1. This was further supported by neutralization and inhibition studies. Importantly, significantly decreased memory B-cell response towards RBD was detected only in the anti-TNFα group, with the most significant reduction in response to Beta VOC (p<0.0008 and p<0.0001, vs. non-anti-TNFα and HC, respectively). Older age was an additional predictor of lower serologic response. Immunoglobulin levels and lymphocyte cell subsets were comparable between the study groups. Infection rate reflected by anti-N Abs was ∼1% in all groups. Safety was comparable in all groups. Conclusion: The, 6-months serologic response to BNT162b2 vaccine, evaluated prospectively, decreased in all subjects, most prominently in patients with IBD treated with anti-TNFα. Importantly, the latter also had the sharpest decline in serologies, the lowest functional activity and lowest RBD specific memory B-cells. Older age is an additional predictor of decreased serologic response. Altogether, waning of COVID- 19 serologic and functional response over, 6 months, specifically in patients with IBD treated with anti-TNFα, supports the need for an early third vaccine dose. (Figure Presented).

4.
Blood ; 138:4876, 2021.
Article in English | EMBASE | ID: covidwho-1582302

ABSTRACT

Objectives: Compared with the general population, patients after allogeneic hematopoietic cell transplantation (HCT) are at higher risk to develop severe disease or die from COVID-19. Immunosuppressive therapy and graft-vs-host disease (GVHD) may abrogate the ability of transplanted patients to mount an adequate immune response to vaccines. We assessed the immune response of patients after allogeneic HCT to the BNT162b2 vaccine (Pfizer-BioNTech) and identified patient and treatment-related factors that predict humoral response in this population. Methods: We conducted an observational prospective cohort study at Rabin Medical Center, Israel. Adult patients after allogeneic HCT were eligible if they had no history of SARS-CoV-2 infection and received the 2-dose BNT162b2 vaccine. The SARS-CoV-2 IgG II Quant (Abbott©,) assay was performed 4-6 weeks after the second vaccine for quantitative measurement of IgG antibodies to spike protein (S-IgG) of SARS-CoV-2. The assay result was considered positive if S-IgG level was ≥50 AU/ml. We used the likelihood ratio of the ROC curves to define the optimal cut-off for continuous variables, χ2 to compare variables on categorical scale and Mann-Whitney to compare medians. To predict seronegativity, we applied logistic regression with the exp(β) as an estimator of hazard-ratio (HR) and the 95% confidence interval (CI) around it. To predict S-IgG levels, we used linear regression. Results: Our cohort included 106 patients. Median age was 65 (range: 23-80) years and 59% were males. Median time from transplant to vaccination was 42 (range: 4-439) months. At time of vaccination, 49% of patients were receiving immunosuppression, while 51% were not. Overall, 14% (15/106) tested negative for S-IgG after vaccination, 27% (14/52) of patients on immunosuppression compared with only 1.8% (1/54) of patients off immunosuppression (p=0.0002). Based on ROC analysis we divided the cohort into patients who were transplanted within (57%) vs. beyond (43%) 4.5y (AUC 0.77, CI: 0.66-0.88). With this cut-off, the sensitivity was 0.93. In univariate analysis, patients vaccinated within 4.5y of HCT (HR: 13.7, 95% CI 1.8-108.5, p=0.013), or still receiving immunosuppression (HR: 9.8, 95% CI 2.1-44.7, p=0.004) and patients with moderate to severe chronic GVHD (HR: 5.9, 95% CI 1.2-29, p=0.03) were more likely to remain seronegative. Age, gender, type of disease and absolute-lymphocyte-count did not predict seronegativity. In MVA, only time, i.e. <4.5y from HCT remained predictive (HR: 10.8, 95% CI 1.2-93.2, p=0.03) (Table 2). Since 93% (14/15) of seronegative patients were transplanted <4.5y, we performed a subgroup analysis of the 57% (60/106) of patients that were transplanted within this time frame. Among these, patients receiving immunosuppression (65%, 39/60) were more likely to remain seronegative (HR: 10, 95% CI: 1.1-93, p=0.03);36% (14/39) of patients on immunosuppression remained seronegative compared with none of the patients off immunosuppression (p=0.002). Among the 43% (46/106) of patients who were vaccinated >4.5y after HCT, 33% (15/46) were still receiving immunosuppression. Yet only 6.6% (1/15) in this subgroup tested negative. Titer levels in seropositive patients ranged between 60 and 80,000 AU/ml (median: 5319). Only a small fraction of this variance is explained by variables tested in this study. Older age (r 2=0.04, p=0.04), shorter time from transplantation (r 2=0.03, p=0.09), the use of corticosteroids (r 2=0.03, p=0.07) or calcineurin inhibitors (r 2=0.06, p=0.013) predicted lower S-IgG levels. The vaccine was well tolerated by most patients. No new cases of GVHD have been reported following vaccination. However, seven patients with chronic GVHD (mild=2;moderate=1;severe=4) reported that GVHD -related symptoms worsened within days following the first, second or both vaccines. Notably, one patient with chronic GVHD developed grade 4 steroid-refractory immune thrombocytopenia 2 weeks after the first vaccine. Conclusion: Overall, 14% of allogeneic HCT recipients had an inadequate ntibody response to the BNT162b2 vaccine. It was only 6.5% among patients off immunosuppression and patients vaccinated >4.5y after HCT. However, inadequate antibody response rate was 36% among recipients vaccinated <4.5y from HCT who were still receiving immunosuppression. These patients should be recognised and instructed to take appropriate precautions. [Formula presented] Disclosures: Yeshurun: Astellas: Consultancy;Jannsen: Consultancy. Wolach: Janssen: Consultancy;Abbvie: Consultancy, Honoraria, Research Funding;Astellas: Consultancy;Amgen: Research Funding;Novartis: Consultancy;Neopharm: Consultancy.

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