COVID-19 Vaccination: Public Health Lessons from a Large Indoor Gathering

COVID-19 transmission rates among vaccinated persons attending large gatherings have not been reported widely. This research was intended to track the potential incidence of COVID-19 among physicians and their families who attended a large in-person gathering in Atlanta in August 2021. After the successful conclusion of a large-scale indoor gathering, we encouraged all attendees to self-report the incidence of COVID-19 illness. In addition, an online questionnaire was disseminated to collect basic information about age, gender, place of residence, vaccination status including the number of doses, type, and date of each dose as well as behavioral and convention factors that would have contributed to the infection rates. Information about current COVID-19 infection status, symptoms, and severity were also collected. We also contacted the attendees through telephone to gather pending information about their COVID-19 status, after attending the meeting. Most attendees were physicians, employees in the healthcare industry or family members of healthcare professionals. Among the 520 participants of the meeting, no COVID-19 illness was reported up to six weeks after attending the convention. As a sub-group analysis, we obtained demographic data from 143 attendees, through an online survey. Among the survey respondents, 43% were over the age of 60 years, 10% over the age of 70 years, 29% and 14% each between 31-45 years and 12-30 years. 53% were women. Almost 99% had received both doses of COVID-19 mRNA vaccine in January and February of 2021. Public health measures including the use of indoor masks, social distancing, and personal hygiene were followed by 76%. None of the convention attendees who responded had any symptoms or tested positive for COVID-19 infection six weeks after leaving the convention. None reported being diagnosed with COVID-19 for at least 30 days before attending the convention. This report confirms the efficacy of COVID-19 mRNA vaccines against protection from COVID-19 illness among participants of large scale indoor gatherings. Our findings support the notion that large-scale events can be successfully conducted among fully vaccinated persons who follow public health guidelines

Aberrant axial mineralization precedes spinal ankylosis: a molecular imaging study in ank/ank mice

Abstract Introduction The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis (ank/ank) mice have a loss of function in the Ank gene, which codes for a regulator of PPi transport. In this study, we used these ank/ank mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging in vivo. Methods Three age groups (8, 12, and 18 weeks) of ank/ank (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system. Results OsteoSense 750 signals in the paw joints were higher in ank/ank mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old ank/ank mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the ank/ank spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation. Conclusions Changes in joint pathology of ank/ank mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in ank/ank mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis

A Fifty-Two-Week, Randomized, Placebo-Controlled Trial of Certolizumab Pegol in Nonradiographic Axial Spondyloarthritis

OBJECTIVE: The natural history of nonradiographic axial spondyloarthritis (SpA) is incompletely characterized, and there are concerns that nonsteroidal antiinflammatory drugs provide inadequate disease control in patients with active disease. This study was undertaken to investigate the effects of certolizumab pegol (CZP), an anti-tumor necrosis factor treatment, in patients with nonradiographic axial SpA with objective signs of inflammation. METHODS: In this ongoing parallel-group double-blind study, adults with active disease were recruited from 80 centers in Australia, Europe, North America, and Taiwan, and were randomized 1:1 to receive placebo or CZP (400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks) in addition to nonbiologic background medication (NBBM). Switching to open-label CZP (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged. The primary end point was the proportion of patients achieving major improvement (MI) (i.e., a \u3e /=2.0-point decrease in the score from baseline or achievement of the lowest possible score [0.6]) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52. RESULTS: A total of 317 patients were randomized to receive placebo plus NBBM (n = 158) or CZP plus NBBM (n = 159). ASDAS-MI at week 52 was achieved in 47.2% (75 of 159) of CZP plus NBBM patients, which was significantly greater (P \u3c 0.0001) than the 7.0% (11 of 158) of placebo plus NBBM patients in whom ASDAS-MI was achieved. Of the placebo plus NBBM patients, 60.8% (96 of 158) switched to open-label treatment before week 52 compared to 12.6% (20 of 159) of the CZP plus NBBM patients. CONCLUSION: Adding CZP to background medication is superior to adding placebo in patients with active nonradiographic axial SpA. These results indicate that remission in nonradiographic axial SpA treated without biologics occurs infrequently, demonstrating the need for treatment beyond nonbiologic therapy. Inc. on behalf of American College of Rheumatology

Instrument selection for the ASAS core outcome set for axial spondyloarthritis

OBJECTIVES: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA). METHODS: An international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments' psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS. RESULTS: The updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments. CONCLUSIONS: The selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1

Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype

The Role of Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) in the Pathogenesis of Ankylosing Spondylitis

Ankylosing spondylitis (AS) is associated with HLA-B*2704 and B*2705 but not with HLA-B*2706 and B*2709. Genome wide studies recently identified ERAP1 as an important genetic association in AS and could be the missing link in the pathogenesis of AS. I studied the implications of the two known actions of ERAP1 on AS pathogenesis. For assessing the peptide trimming function, surface HLA-B27 and MHC-I free heavy chain (FHC) expression on peripheral blood mononuclear cells of AS patients were studied. Subsequently, in an in vitro system of C1R cells expressing different AS-associated and AS-neutral HLA-B27 subtypes, I studied the effect of ERAP1 suppression on HLA-B27 and FHC expression. To assess the cytokine receptor shedding function, I studied serum cytokine receptor level variation with ERAP1 polymorphisms and its relationship to disease activity in AS patients. Finally, I studied the effect of variants of ERAP1 and other members of the antigen presentation machinery on radiographic severity in AS patients. AS patients with the major allele of the ERAP1 rs27044 polymorphism had higher FHC expression on monocytes. In C1R cells ERAP1 suppression led to an increase in intracellular FHC (IC-FHC) and B27-peptide complexes identified by a special MARB4 antibody, but only in C1R cells expressing the AS-associated subtypes HLA-B*2704 and B*2705. ERAP1 variants had no effect on serum cytokine receptor levels. Baseline radiographic severity was associated with ERAP1 polymorphism in univariate analysis only. LMP2 variants were associated with baseline radiographic severity in multivariate analysis. ERAP1 affects peptide presentation and FHC formation by HLA-B27 and could be the missing link in the pathogenesis of AS. ERAP1 through its differential HLA-B27 subtype interaction could explain why certain subtypes of HLA-B27 are associated with AS while others are not. Larger studies are required to look closely at the effect of ERAP1 on radiographic severity and progression in AS.Ph

Disease modification in axial spondyloarthritis

The concept of "disease modification" refers to an intervention that modifies the natural clinical course of the disease along with improvement of symptoms. With regard to this, providing treatment that improves clinical signs and symptoms of axial spondyloarthritis (axSpA) and that impacts disease pathogenesis by slowing/halting bone formation is the main goal of this concept. It has been proven that currently available treatments including biologics and nonsteroidal anti-inflammatory drugs have a symptom-modifying effect in axSpA. The body of evidence showing a beneficial effect of biologic therapy on spinal damage is growing. In this article, by centralizing new bone formation as a main target of disease modification, we reviewed molecular mechanisms related to new bone formation, relevance of imaging studies on assessment of disease progression, clinical predictors of new bone formation, and disease-modifying properties of currently available treatments in axSpA. (C) 2019 Elsevier Ltd. All rights reserved

Alterations of Bone Mineral Density, Microarchitecture and Strength in Patients with Ankylosing spondylitis: a Cross-sectional Study using High-resolution Peripheral Quantitative Computerized Tomography

Patients with ankylosing spondylitis (AS) have high fracture risk. BMD, bone microarchitecture and strength determine bone strength. However, the effect of AS on bone microarchitecture and strength is not studied yet. This study aimed to analyze how AS affects bone microarchitecture and strength. Volumetric BMD (vBMD) and microarchitecture were measured using HRpQCT, and bone strength was estimated using finite element analysis. Multivariable linear regression was used to analyze the effect of AS on HRpQCT and FEA parameters. There were 44 AS patients and 85 non-AS subjects. In multivariable linear regression models, AS patients had lower volumetric BMD, cortical thickness, BV/TV and higher cortical porosity and trabecular separation when compared to non-AS controls. FEA parameters such as bone stiffness and stress were also abnormal in AS patients. To conclude, it was found that volumetric BMD, trabecular and cortical microarchitecture as well as FEA parameters were worse in AS patients than non-AS subjects. These abnormalities might partly explain the high fracture risk in patients with AS.M.H.Sc