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1.
Background

Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood.

Objectives

COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination.

Methods

Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs.

Results

A total of 5.6% (n?=?320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n?=?168) compared with 100% of healthy controls (n?=?205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p?=?0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p?=?0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine.

Conclusion

SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

  相似文献   
2.
Galvain  Thibaut  Hill  Ruaraidh  Donegan  Sarah  Lisboa  Paulo  Lip  Gregory Y. H.  Czanner  Gabriela 《Drug safety》2022,45(11):1349-1362
Drug Safety - Atrial fibrillation (AF) is a major cause of stroke. Anticoagulants substantially reduce risk of stroke but are also associated with an increased risk of bleeding. Because of that,...  相似文献   
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Portilla-Fernández  Eliana  Hwang  Shih-Jen  Wilson  Rory  Maddock  Jane  Hill  W. David  Teumer  Alexander  Mishra  Pashupati P.  Brody  Jennifer A.  Joehanes  Roby  Ligthart  Symen  Ghanbari  Mohsen  Kavousi  Maryam  Roks  Anton J. M.  Danser  A. H. Jan  Levy  Daniel  Peters  Annette  Ghasemi  Sahar  Schminke  Ulf  Dörr  Marcus  Grabe  Hans J.  Lehtimäki  Terho  Kähönen  Mika  Hurme  Mikko A.  Bartz  Traci M.  Sotoodehnia  Nona  Bis  Joshua C.  Thiery  Joachim  Koenig  Wolfgang  Ong  Ken K.  Bell  Jordana T.  Meisinger  Christine  Wardlaw  Joanna M.  Starr  John M.  Seissler  Jochen  Then  Cornelia  Rathmann  Wolfgang  Ikram  M. Arfan  Psaty  Bruce M.  Raitakari  Olli T.  Völzke  Henry  Deary  Ian J.  Wong  Andrew  Waldenberger  Melanie  O’Donnell  Christopher J.  Dehghan  Abbas 《European journal of epidemiology》2021,36(11):1143-1155

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

  相似文献   
7.
Journal of Thrombosis and Thrombolysis - Alteplase treatment can cause a systemic coagulopathy although the incidence and contributory factors are unknown in pulmonary embolism (PE). Fixed-dosing...  相似文献   
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Purpose

The purpose of this study was to determine the prevalence of respiratory and/or physical fitness health problems in adolescent (ages 18–21) water pipe (WP) smokers (with or without cigarette smoking), cigarette-only smokers, and nonsmokers.

Methods

A comparative four-group study design was used to recruit a non–probability sample of 153 WP smokers only, 103 cigarette smokers only, and 102 cigarette+WP smokers along with 296 nonsmokers. Our hypothesis was that youth who smoked WPs and/or cigarettes would report more respiratory problems and/or poorer physical fitness than those who did not smoke.

Results

The results showed that coughs were significantly associated with smoking in all three of the smoking groups (p < .05). Cigarette-only smokers reported the most adverse outcomes with more wheezing, difficulty breathing, and less ability to exercise without shortness of breath. A dose-response analysis showed similar patterns of adverse health effects for both WP and cigarette smokers. The combined use of both products was not appreciably worse than smoking one product alone. This could be due to cigarette+WP smokers' reporting using less of the respective products when only one product was smoked.

Conclusions

Even during the adolescent years, WP and/or cigarette smoking youth experienced reportable negative health effects.  相似文献   
10.
Many techniques have been proposed to address the problem of increased lateral adiposity in patients undergoing mastectomy, however, there is no standard approach. This cosmetic deformity at the lateral end of the mastectomy scar, also known as a dog ear, is especially common in obese patients. This defect can be unsightly and uncomfortable. We describe a technique for creating a winged incision to eliminate the dog ear deformity. The Angel Wings Incision results in tissue flaps that create a smooth body contour upon closure in patients with increased lateral adiposity. The technique is reproducible, aesthetically pleasing, and improves patient satisfaction.  相似文献   
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