2 research outputs found
156. The immunological response to COVID-19 vaccination in patients with ANCA-associated vasculitis treated with rituximab
No full textBackground: Landmark clinical trials have demonstrated efficacy of SARS-CoV-2 vaccination in preventing severe COVID-19, however most participants in these trials were healthy volunteers. In particular, vaccine performance in immunosuppressed individuals, such as those with ANCA-associated vasculitis (AAV) is unknown. Rituximab (RTX) has become an important treatment for AAV, however this B cell depleting agent has previously evidenced impaired humoral response following influenza vaccines and now there are similar concerns regarding reduced immunogenicity to SARS-CoV-2 vaccines. In this study, we aimed to characterise the immune response of the ChAdOx1 (Astra Zeneca) vaccine in RTX treated AAV patients. (1)
Methods: The OCTAVE trial was a UK based, multi-centre, multi-disease prospective cohort study designed to assess the immune response to SARS-CoV-2 vaccination in immunosuppressed individuals, including patients with AAV treated with RTX within the prior 12 months. Peripheral blood samples were taken for quantitative IgG response to SARS-CoV-2 spike antigen (anti-S) and IFN T cell responses to SARS-CoV-2 antigens at baseline (where possible), immediately prior to second SARS-CoV-2 vaccine dose and 28 days post-second dose. Results were compared to a group of healthy controls from the UK PITCH (Protective Immunity from T cells in Healthcare workers) study.
Results: Of 455 cases recruited for full immune response analysis, 29 had AAV and 93 were healthy controls. Baseline demographics were described (Table 1). At 4 weeks post-second SARS-CoV-2 vaccine dose 27.6% (8/29) AAV patients demonstrated anti-S seroconversion, compared to 100% (93/93) healthy controls. Further, 89.7% of AAV patients had an anti-S antibody response that was less that the lowest titre achieved in the healthy control group. When compared to other OCTAVE disease cohorts, AAV patients had the lowest serological conversion rate and lowest median anti-S titre. The median SARS-CoV-2 specific T cell response in the AAV group was 98 (IQR: 40-178) IFN secreting T cells / 106 peripheral blood
mononuclear cells (PBMC), while the equivalent result in the healthy control group was 60 (IQR: 20-136) (Table 1).
Conclusions: Early analysis indicates that individuals with AAV have a substantially blunted antibody response to SARS-CoV-2 compared to a healthy population, but a comparable T-cell response. This may suggest that AAV patients have some degree of protection from SARS-CoV-2 vaccination, but clinical evaluation of this population is awaited. Analyses of additional immunological parameters, such as neutralising antibody responses and broader immunoglobulin analysis, are ongoing.
Disclosures: None relevant to this study.
Table 1: Demographics and anti-Spike seroconversion at 4 weeks in healthy controls and AAV patients
Healthy controls
AAV
N (whole cohort)
231
30
Age; N (%)
18 – 40
186 (81%)
10 (33%)
50 – 64
37 (16%)
12 (40%)
65 +
7 (3%)
8 (27%)
Missing data
1 (0%)
0 (0%)
Sex; N (%)
Female (%)
156 (68%)
16 (53%)
N (full immune response at 4 weeks)
93
29
Anti-S seroconversion; N (%)
93 (100%)
8 (27.6%)
Anti-S titre; U/ml [Median(IQR)]
11,514
(3,324-23,302)
0.4
(0.4-24.5)
IFN secreting T cells; per 106 PBMC [Median(IQR)]
60
(20-136).
98
(40-178
Some Contributions to the Theory of Sampling.
No full textThe work Presented here had originated from a pioneering paper by Basu1 and is essentially an extension of his ideas to different problem in sample surveys. The whole word mainly consists in deriving estimators uniformly better than those usually adopted in with replacement schemes.in with replacement sampling schemes, the \u27order-statistic\u27 (distinct sample unite arranged in an ascending order of their unit-indices) forms a sufficient statistic. Therefore, if any estimator (e.g., say of the population man) does not depend on the \u27order-statistic\u27, it can be uniformly improved by the use of the Rao-blalckwell theorem. The author has not hesitated to use this powerful theorem to derive improved estimators- It T is a sufficient statistic, for any convex (downwards_ lose function, an estimator uniformly better than g(S) (where g(S) is some estimator based on the sample S) is given by E[g(S)1T]=S\u3eΣT g(S) p(S)/ S\u3eΣ T p(S)The whole theais ie divided into eight chapter and two ppendioen. Che pter II hau been davoted to the problen of finting moente of dietinet uni te that appear in a aple, thie chapber haa teen very helprul in getting now roulte in subeequent ehaptere whieh vould haw been, othervia, dieioult te obtain. It may te podntod out shat it we thie ohnpter vhiah ultiantely led the uthar te write don the theute. It hae been the authorte endeavour to prent selfcontadned trea tamt of the problens dinouneod haredn. N ia for thia and for the purpoee of completens that soe problene already oonaidered y other authom, ae alno given in a stapli fied fam. TheProblems with which have been dnly oonermel, are the entdmetion of the poulatton ana ? (or total), ste aqure nd the population varianoe. The problan of finting unbiaaed entinstor of the saqure of the population mean arone whi le finding undad varianoe entiantore of the eatiatore af . The following teahnique for finding waldaad varianoe eetimtore hae been uaed- if ia an unhdased catian tor of , an unbiaaed estigtor of v(4) ie givenly
