Detection of SARS-CoV-2 Spike-Protein-Specific Antibodies after Vaccination via Nasal and Buccal Swabs: Prospects for Mass Scale Immunity-Screening in Large Populations

Background: Humoral immunity after SARS-CoV-2 vaccination has been extensively investigated in blood. Far less is known, however, about the potentially induced mucosal immunity. Aim of this study was to develop an ELISA method in order to determine the prevalence of IgG and IgA SARS-CoV-2 spike-protein-specific antibodies (Abs) in buccal and nasal surfaces of vaccinees after full vaccination with BNT162b2, mRNA-1273, ChAdOx1 or combination. Method(s): To this end, we prospectively analyzed 69 adult individuals after signed written consent who received their first vaccine dose between February and July 2021. Detection of IgG and IgA Abs was performed using the semi-quantitative ELISA assay from EUROIMMUN for both blood and swab samples after protocol modification for the latter. The eluates of the nasal and buccal swabs were analyzed undiluted while the same cut-off was set as for the serum assay. The samples were taken at regular intervals to ensure systematic recording of Ab course before and after each vaccination dose. Result(s): After second dose all study subjects developed IgG anti spike Abs in serum, yet 5.9% of them remained negative for IgA. In buccal swabs, positivity rates were 81.2% and 53.1% and in nasal swabs 84.1% and 90.6% for IgG and IgA, respectively. The IgG Abs in buccal swabs correlated more consistently with the respective measurements in blood with a correlation coefficient of r=0.74 while the IgA assay gave less concordant results. It is of note that IgA Abs appeared to be significantly more prevalent in the nasal compared to the buccal mucosa. Adjustment of the assay cut-off as to IgG antibody detection in buccal swabs from 1.1 to 0.2 conferred a sensitivity of 91.8% and a specificity of 100% in a total of 520 comparison measurements. Conclusion(s): In conclusion, our findings confirm a weaker yet clear prevalence of Abs in mucosal surfaces after full vaccination against SARSCoV- 2 with IgA anti-spike Abs being significantly more prevalent in the nasal cavity. Our method for IgG Ab detection in buccal swabs could be expanded to other pathogens of interest and serve as a reliable alternative to standard serum assays especially in the context of immunity screening of large populations.

Proton pump inhibitors in systemic sclerosis: a reappraisal to optimise treatment of gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease (GERD) is associated with substantial morbidity in patients with systemic sclerosis. Although the introduction of proton pump inhibitors (PPIs) into clinical care represents a major achievement in the management of gastro-oesophageal problems in systemic sclerosis, PPIs are seldom fully effective in patients with systemic sclerosis, and the use of maximum PPI doses is a very frequent clinical practice. However, there is little evidence to support the empirical use of PPIs in systemic sclerosis. This scarcity of evidence is especially relevant with regards to the safety concerns of long-term exposure, which have been raised in the general population. The purpose of this Viewpoint is to highlight the substantial beneficial impact of PPIs on GERD in patients with systemic sclerosis, while considering the potential adverse effects in this patient population. Furthermore, we highlight the unmet needs of people with systemic sclerosis and GERD and propose an agenda for future research to optimise the safe and effective use of PPIs in systemic sclerosis. Copyright © 2022 Elsevier Ltd

STRESS-ASSOCIATED INCREASES in RHEUMATOID ARTHRITIS DISEASE ACTIVITY and FLARES during the COVID-19 PANDEMIC

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has spurred global action. Beginning in March of 2020, the Southern California COVID-19 pandemic response to limit virus transmission was characterized by mandated lockdowns and quarantines, resulting in signifcant stressors for rheumatology patients and potentially threatening their disease. Objectives: To examine factors associated with changes in rheumatoid arthritis (RA) disease activity and fares in the COVID-19 pandemic. Methods: RA patients identifed by ICD-9/10 codes and active email addresses within a University of California, Los Angeles (UCLA) Rheumatology database were sent surveys via email in July and November of 2020. The survey was UCLA Institutional Review Board approved and included electronic consent and questions related to: perceptions of disease activity/remission via Routine Assessment of Patient Index Data 3 (RAPID3), fare frequency, RA fare questionnaire (RA-FQ), Perceived Stress Scale (PSS-4), and pandemic impact on stress (I.e. emotional state, apprehension, panic, helplessness, work, home, fnancial, and social distancing stress). Demographics were extracted from electronic medical records. Results were examined via descriptive analyses, Pearson correlations, and chi-square test for comparisons plus linear stepwise regressions where appropriate to evaluate the relationship between stress measures, RA disease activity, and fare frequency and severity. Results: Among 5037 patients surveyed, 361 in July and 4676 in Novem-ber,1128 (22.4%) responded. The study population demographics were: mean age of 57.5 ± 15.1 years, 79.4% female, racially diverse (69.6% Caucasian, 13.7 % LatinX, 9.5 % Asian, and 4.9% Black), and 62% seropositive (CCP and/or RF). Perceived disease activity and remission remained stable in most patients with 719 reporting no fares, and 409 in current fares at the time of the survey (Table 1). A minority reported perceived increases in disease activity which were associated with multiple aspects of perceived stress. At survey completion, 346 had not experienced fares, 290 had experienced one fare, and 492 had experienced multiple fares. Use of DMARDs was associated with lack of fare versus current fare (77.8% versus 71.6%, p = 0.02). The use of conventional synthetic, biologic, or targeted synthetic DMARDs were not associated with fare while current corticosteroid use was associated with fare (9.3% without fare and 20.8% with fare, p < 0.0001). Current fare was associated with increased PSS-4 scores (odds ratio (OR): 1.17 (95% confdence interval: 1.12-1.22, p < 0.0001). Figure 1 describes the odds ratio of experiencing aspects of stress with the presence of RA fare. Conclusion: In a large survey population of RA patients during the COVID-19 pandemic, multiple aspects of stress were found to correlate with RA disease activity and fare.

The impact and outcome of COVID-19 on systemic sclerosis patients from the european scleroderma trial and research group (EUSTAR)

Background: Coronavirus disease-19 (COVID-19) has been a major clinical challenge worldwide. Sex, age and comorbidities have been associated with worse outcome in the general population. Systemic sclerosis (SSc) is a severe, autoimmune disease with frequent multi-organ involvement. Objectives: To assess the impact of COVID-19 and to determine factors associated with worse outcome in SSc patients from the European Scleroderma Trial and Research (EUSTAR) database. Methods: SSc patients from the EUSTAR database with COVID-19 were prospectively collected between 15.03.-31.12.2020. Two outcomes were chosen: (1) hospitalization;and (2) severe outcome defined as either non-invasive ventilation, mechanical ventilation/extracorporeal membrane oxygenation (ECMO) or death. General risk factors assessed were sex, age and number of comorbidities. SSc related risk factors were SSc subtype, autoantibodies, disease duration, SSc associated organ manifestations including interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), cardiac, gastrointestinal (GI), and musculoskeletal involvement;digital ulcers (DU), CRP at last visit, renal disease (scleroderma renal crisis and SSc associated renal insufficiency), modified Rodnan skin score (mRSS) and immunosuppressive treatment. Descriptive statistics and logistic regression models were applied. Results: In total, 178 European SSc patients with COVID-19 were registered with a median observation time of 5.5 weeks (Table 1). 95 patients (53%) could recall SAR-Cov-2 contact, while 47 (26%) had no contact. 156 (88%) were symptomatic at COVID-19 onset with fever, cough, malaise and dyspnea being most prevalent. Over the disease course, 63 (36%) developed pneumonia. In total, 67/176 (38%) were hospitalized which were in 84% due to COVID-19. 41/170 (24%) had a severe outcome including 21 (12%) deaths. 128 (72%) recovered completely, while 14 (8%) complained of sequela, with 7 (50%) stating respiratory complications. Age, non-SSc comorbidities, presence of ILD, PAH and SSc associated renal or cardiac disease were numerically associated with hospitalization and severe outcome (Table 1). Univariable logistic analyses for hospitalization and severe outcome are shown in Figure 1. In multivariable logistic regression, age (OR 1.03, 95%CI 1.01-1.07, p=0.019), presence of non-SSc comorbidities (OR 2.52, 95%CI 1.16-5.47, p=0.019) and SSc-related renal disease (predicting success perfectly) were associated with hospitalization and for severe outcome age (OR 1.05, 95%CI 1.01-1.08). Conclusion: SSc patients at older age, with non-SSc comorbidities, SSc related renal disease or ILD are at risk of a more severe outcome and should follow precautions to avoid COVID-19 infections and need careful monitoring in case of COVID-19.