Refractory hypereosinophilia associated with newly diagnosed rheumatoid arthritis following inactivated BBV152 COVID-19 vaccine.
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ABSTRACT:
SUBMITTER: Singh R
PROVIDER: S-EPMC9088458 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Somatic mutations contribute to tumorigenesis. Although these mutations occur in all proliferating cells, their accumulation under non-malignant conditions, such as in autoimmune disorders, has not been investigated. Here, we show that patients with newly diagnosed rheumatoid arthritis have expanded CD8+ T-cell clones; in 20% (5/25) of patients CD8+ T cells, but not CD4+ T cells, harbour somatic mutations. In healthy controls (n=20), only one mutation is identified in the CD8+ T-cell pool. Mutations exist exclusively in the expanded CD8+ effector-memory subset, persist during follow-up, and are predicted to change protein functions. Some of the mutated genes (SLAMF6, IRF1) have previously been associated with autoimmunity. RNA sequencing of mutation-harbouring cells shows signatures corresponding to cell proliferation. Our data provide evidence of accumulation of somatic mutations in expanded CD8+ T cells, which may have pathogenic significance for RA and other autoimmune diseases.
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Project description:Our objective was to estimate the percentage of patients with incident rheumatoid arthritis (RA) who were seen by a rheumatologist within 3, 6 and 12 months of suspected diagnosis by a family physician, and assess what factors may influence the time frame with which patients are seen.Ontario, Canada.Over 2000-2009, we studied patients with incident RA who were initially diagnosed by a family physician.We assessed secular trends in rheumatology encounters and differences between patients who received versus did not receive rheumatology care. We performed hierarchical logistic regression analyses to determine whether receipt of rheumatology care was associated with patient, primary care physician and geographical factors.Among 19 760 patients with incident RA, 59%, 75% and 84% of patients were seen by a rheumatologist within 3, 6 and 12 months, respectively. The prevalence of initial consultations within 3 months did not increase over time; however, access within 6 and 12 months increased over time. Factors positively associated with timely consultations included higher regional rheumatology supply (adjusted OR (aOR) 1.35 (95% CI 1.13 to 1.60)) and higher patient socioeconomic status (aOR 1.18 (95% CI 1.07 to 1.30)). Conversely, factors inversely associated with timely consultations included remote patient residence (aOR 0.51 (95% CI 0.41 to 0.64)) and male family physicians (aOR 0.88 (95% CI 0.81 to 0.95)).Increasing access to rheumatologists within 6 and 12 months occurred over time; however, consultations within 3 months did not change over time. Measures of poor access (such as proximity to and density of rheumatologists) were negatively associated with timely consultations. Additional factors that contributed to disparities in access included patient socioeconomic status and physician sex.
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| S-EPMC7825810 | biostudies-literature
Project description:BackgroundBBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.MethodsWe conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%.FindingsBetween April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61).InterpretationThis study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.FundingNone.TranslationFor the Hindi translation of the abstract see Supplementary Materials section.
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