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Background: SARS-CoV-2 vaccines offer the most effective way to reduce the risk of severe COVID-19. Recent data indicate sufficient immune response after vaccination in most patients with infammatory rheumatic diseases (IRD) on immunomodulatory treatments. Objectives: To investigate the clinical profile of SARS-CoV-2 breakthrough infections among double and triple vaccinated patients with IRD. Methods: Data from the German COVID-19-IRD registry, collected by treating rheumatologists between February 2021 and January 2022 were analysed. Patients double or triple vaccinated against COVID-19 ≥14 days prior to proven SARS-CoV-2 infection were identifed, and type of IRD, vaccine, immunomodulation, comorbidities and outcome of the infection were compared with 737 unvac-cinated IRD-patients with COVID-19. Results: In total, 271 cases of breakthrough infections were reported, 250 patients (91%) had received two doses of vaccines, 21 (9%) patients three. More than 70% of the patients received Pfzer/Biontech vaccine for the frst, second and third vaccination. The median time from second/third vaccine dose to infection was 148 days (range 14-302) days. Most of the patients were diagnosed with infamma-tory joint diseases (Table 1). Most of the patients were treated with methotrexate (Table 1). The use of Januskinase inhibitors(i) was more frequently reported in double vaccinated patients (10.4% vs 4.8%), whereas tumor necrosis (TNF)i were reported more often in triple vaccinated patients (33.3% vs. 22.8). Hospitalisation rate was higher in unvaccinated IRD-patients than in vaccinated ones, while fatality rate was similar in unvaccinated and double vaccinated patients. Although the rate of comorbidities and median age were higher in triple-vaccinated patients, infected patients showed a lower rate of hospitalisation, neither COVID-19 related complications, nor the need of oxygen treatment or death. Conclusion: In this cohort of triple-vaccinated IRD patients no fatal courses and no COVID-19 related complications were reported, although median age and rate of comorbidities were higher compared to double-vaccinated and unvacci-nated patients. These results support the general recommendations to reduce the risk of severe COVID-19 disease by administering three doses of vaccine, especially in patients with older age, presence of comorbidities, and on immuno-modulatory treatment.
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Background: At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) pandemic, the influence of anti-infammatory therapy on the course of SARS-CoV-2 infection in patients with infammatory rheumatic diseases (IRD) was unknown. In the meantime, several data indicate an association of severe courses of COVID-19 with the use of ritux-imab (RTX). Objectives: To gather further knowledge about SARS-CoV-2 infections in RTX-treated IRD patients, data from the German COVID-19-IRD-registry were analysed. Methods: Hospitalisation was used as a surrogate of COVID-19 severity. Baseline characteristics, disease features, medication and outcome of COVID-19 were compared in RTX-treated inpatients and outpatients. Results: In total, 3592 cases were reported in the registry, which included 130 RTX patients (3.6%) for our analysis. RTX-treated inpatients were older than RTX-treated outpatients (median age 63 y vs 56 y, p=0.007). Patients with granulomatosis with polyangiitis treated with RTX (n=32) showed a significant higher COVID-19 related hospitalisation rate (33% vs 11%, p=0.005), which was not the case for patients with rheumatoid arthritis (49% vs 50%). Cardiovascular comorbidities were reported more frequently in hospitalised RTX-treated patients (20% vs. 6%, p=0.032). More than 50% of the RTX-treated inpatients developed COVID-19 related complications, e.g. acute respiratory distress syndrome. The median time period between the last RTX treatment and SARS-CoV-2 infection was shorter in inpatients than in non-hospitalised patients (3 (range 0-17) vs. 4 months (range-29), p=0.039). The COVID-19 related mortality rate was 14% (n=19) in RTX-treated IRD patients. In RTX-treated inpatients and outpatients, there were no relevant differences with respect to the use of concomitant glucocor-ticoids or other disease modifying anti-rheumatic drugs, disease activity, median last RTX dose or median number of immunomodulatory drugs prior to RTX treatment. Conclusion: In addition to general risk factors, such as age and comorbidities, it is already known that IRD patients treated with RTX show a higher rate of severe COVID-19. In our registry, RTX-treated patients with granulomatosis with polyangiitis appear to be at even higher risk to develop severe COVID-19 compared to other IRD. Moreover, the shorter the time since the last RTX treatment, the higher seems to be the risk of developing severe COVID-19. This might be explained by a more profound B-cell depletion in the frst weeks after RTX treatment warranting further studies.
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Background: Axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) may have a profound impact on health-related quality of life (HRQoL) and sleep despite effective treatment. Objectives: To assess sleep and HRQoL in SpA and determine associated factors. Methods: Monocentric questionnaire-based assessment of HRQoL, function, sleep and depression in 314 SpA patients (n=168 PsA, n=146 axSpA). Results: Under effective treatment 138 SpA patients (46.5%) demonstrated abnormal sleep behaviour. 49.3% reported not being able to sleep through the night, with 6.1 % needing sleeping pills. 11.9% indicated feeling unrefreshed most mornings. Abnormal sleep behaviour was associated with female sex (p=0.005), HLAB27 (p=0.034), functional impairment (p=0.001) and depression (p<0.001). Patients reporting unrestful sleep had signifcantly more depressive symptoms (p<0.001) and highly reduced physical and mental HRQoL (p<0.001). Satisfaction with health was rated signifcantly lower (p<0.001). Patients with axial involvement (axSpA/axPsA) reported worse sleep quality (p=0.002) and waking too early (p=0.038) despite 73.7% receiving biologics. Sleep quality and early awakening correlated with BASDAI (p<0.001). Smokers had a reduced HRQoL (p=0.018) despite younger age (p=0.008). Female patients had worse sleep quality (p<0.001), needing more time to fall asleep (p=0.022), not being able to sleep through the night (p=0.026) and feeling unrefreshed in the morning (p<0.001). They had a reduced physical (p=0.019) and mental HRQoL (p=0.003), more depressive symptoms (p=0.040) and lower functional capacity (p=0.002). Functional capacity was associated with younger age (p<0.001), sex (p=0.042), smoking (p=0.008), sleep quality (p<0.001) and depression (p<0.001). 66.2% of patients have been assessed longitudinally, before and 3y later during COVID19 pandemic. Physical and mental HRQoL were stable over time. Functional capacity had decreased slightly. Subjective QoL during the COVID19 pandemic was not reduced compared to before. Regarding depressive symptoms, there was a mild but signifcant improvement over time (p=0.019). Furthermore, we observed an improvement of environmental QoL (p=0.034) during COVID pandemic. Overall subjective QoL as well as satisfaction with health did not change signif-cantly. Patients who had changed therapy (37% of the cohort) still had a reduced physical HRQoL (p=0.022) as well as signifcantly more depressive symptoms (p=0.010) and perceived their overall QoL as being worse (p=0.016). Conclusion: Despite treatment many SpA patients have a reduced HRQoL and impaired sleep quality with signifcant differences between male and female patients. Impact of COVID19 pandemic was low.
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Background: Patients with rheumatic and musculoskeletal diseases (RMD) might have an increased risk for infection due to their immunomodulatory treatment, secondary to their disease and comorbidities. Recent studies suggest a decreased risk of severe COVID-19 in RMD-patients treated with biologics. Objectives: The aim of this study was to assess courses of RMD patients treated with TNF-inhibitors (TNF-I) included in the German COVID-19 registry. Methods: In the German physician-reported COVID-19-RMD registry, patients with an RMD and confirmed SARS-CoV-2-infection were documented (data entered between March 30, 2020 and January 30, 2021). We analysed TNF-I treated patients, their course and outcome of the infection. Data were compared to RMD-patients treated with other immunomodulatory drugs (OID) than TNF-I. Results: A total of 269 patients were treated with a TNF-I (57% female) compared to 874 patients who were treated with OID (68% female). Median age was 52 years (range: 19-87) in the TNF-I-group versus 58 years (range: 18-91) in the OID-group. Rheumatoid arthritis was the most common diagnosis (38% in TNF-I-group vs. 52% in the OID-group), followed by ankylosing spondylitis (32% vs. 6%), psoriatic arthritis (22% vs. 11%) and other RMD (9% vs. 31%). Adalimumab (35%) and etanercept (35%) were the most frequently used TNF-I (tab. 1). Glucocorticoids (GC) were used in 22% of TNF-I-treated patients and in 42% of the OID-group. Under TNF-I, stable disease was reported prior to the SARS-CoV-2-infection in 53% of the patients (OID-group: 47%), followed by low disease activity in 35% (OID: 34%), moderate disease activity in 6% (OID: 12%) and high disease activity in 4% (OID: 3%). Most frequent comorbidities were arterial hypertension (29% under TNF-I vs. 35% under OID), diabetes (8% vs. 11%) and cardiovascular diseases (7% vs. 12%). The most common reported COVID-19 symptoms were dry cough (57% vs. 55%), fever (53% vs. 61%) and fatigue (50% vs. 49%). Hospitalization due to SARSCoV infection was required in only 12% of the TNF-I-treated cases vs. in 29% in the OID-group. Oxygen treatment was necessary in 5% of the patients under TNF-I compared to 22% under OID and invasive ventilation in 2% in the TNF-Igroup compared to 6% under OID. Most notably, no fatal courses of COVID-19 were reported among the 269 RMD-patients treated with TNF-I versus 49 deaths in the 874 cases (5.6%) treated with OID. Focussing on the hospitalizated TNF-I patients, the rate of concomitant GC use (p<0.001) and higher disease activity (p=0.005) was significant higher (tab.1). Conclusion: High or moderate RMD-disease activity is an important factor associated with severity of COVID-19 including mortality. In this large cohort RMD patients treated with TNF-I show a low hospitalisation rate and no fatal course. This is reassuring for patients and treating rheumatologists to use TNF-I to control RMD disease activity. The use of glucocorticoids and high disease activity seem to counteract possible protective effects of TNF-I.
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Background: The current pandemic constitutes an entirely new situation for patients as well as physicians. The insecurity of the early phase, shutdowns, increasing infection rate and appearing SARS-CoV2 mutations have created a situation that makes live difficult especially for chronic diseases i.e. patients with rheumatic and musculoskeletal diseases (RMD) and their treating physicians. The psychosocial burden that is created by this special situation is completely unknown and is estimated to be higher in patients than in the general population. Objectives: In order to measure the impact on our patients, the German COVID19-Rheuma patient survey was set up in April 2020, during Germany's first shut down. Methods: The German COVID19-Rheuma patient survey is a patient reported longitudinal online survey where patients with RMD who registered between April and July 2020 are asked on a monthly base using an online survey on social, personal, medical factors, whether a COVID19 infection occurred, isolation measures were changed and scores regarding stress and anxiety are recorded. Between April and July 2020, 637 patients registered and completed a first survey. Up to January 2021, about 400 patients are still enrolled. Here we present an interim analysis of the first 6 months regarding patients that were enrolled in April and May during the first shut-down. This first analysis compares the situation in the first lockdown to July, a phase with very low infection numbers in Germany, and to November, the beginning of the second lockdown. Results: 150 patients (87% female) were enrolled in April/early May 2020. Mean age was 48 years (range 11-89). The majority of patients suffered from rheumatoid arthritis (51%), followed by psoriatic arthritis (17%), other spondyloarthropathies (10%) and connective tissue diseases (10%). The majority of patients received antirheumatic therapies: 32% glucocorticoids (GC), 31% cDMARDs, 21% TNF inhibitors, 7% Jak inhibitors, and 9% other biologicals. Of the patients treated with GC, 25% were on GC monotherapy. In the first lockdown, 26% of patients were working remotely and 24% were self-isolating (doubles included). Additionally, 48% were using masks that were not mandatory at that time and 41% were using disinfection in a regular manner. The rates for remote work and self-isolation did not change significantly over time while the mask use increased to 98% with the official obligation to do so. The use of disinfectants increased to 88% in November. Regarding disease activity, no change in patient global assessment could be observed over time (4.3 ± 2.5 vs. 4.0 ±2.6 and 4.0 ± 2.5). Self-reported pain was also stable over time as were sleep disturbances. While 48.2% of patients who were receiving physiotherapy paused in April, only 10 and 14% did so in July and November, respectively. 11% of the patients paused their medication in the first lockdown, whereas only 2.75% did so in July and 3.4% in November. Contact with the treating rheumatologist was maintained over time in the majority of cases. Conclusion: While in the beginning of the pandemic the insecurity was considerable and the concern that the fear for infection would lead to inadequately treated patients with RMDs, we here show for the first time that on the one hand our patients were timely in taking adequate measures to keep themselves safe (e.g. self-isolating, mask use) and adapted to the clinical situation in not pausing their medication. Altogether, in this alert cohort, the pandemic did not lead to an increase of patient-reported disease activity in the first six months.
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Background: Freiburg was among the most heavily affected German cities during the first wave of Sars-Cov-2 infections in spring 2020. Consequently, the University Medical Center Freiburg was one of the first hospitals in Germany to treat Covid19 patients. Objectives: To assess the proportion and characteristics of health care workers (HCW) that have been infected during that first wave SARS-CoV-2 serum IgG and IgM antibodies were measured. Methods: HCW (n=902, mean age: 40.7 years) participated in this study, and filled out an epidemiological questionnaire. Serum samples were analysed for SARS-Cov-2 IgG/IgM antibodies via rapid diagnostic test (RT) and via ELISA. Statistical analyses were performed using STATA 14.2. An exposure prevention score was developed to quantify the adherence to preventive measures in everyday life. Results: 902 HCW were tested by RT, and 499 by ELISA. In total, 11.5% of recruited HCW were antibody-positive in the RT, 12.2% in the ELISA. 87.5% of RT positives, 98% of ELISA-positives reported symptoms, compared to 74.6% and 78% of negatives, respectively. Symptoms such as cough (57%/46%), loss of smell and taste (34%/5.2%), fatigue (68%/45%), fever (48%/24%), body aches (45%/22%), and headaches (58%/46%) were reported by significantly more RT positives compared to negatives. The respective differences were even more pronounced (p<0.001) among ELISA-positives compared to negatives with >50% of those positive reported impaired smell or taste compared to less than 7% among the group of ELISA-negatives (p<0.00001). In logistic regression models, shift work and belonging to the lowest quartile of the exposure prevention score were significantly associated with seropositivity in both tests. Exposure towards children was inversely associated with seropositivity, however, in the finally adjusted model only significant for those that were RT-positive, but not ELISA-positive, reflecting the lower specificity of the former. Conclusion: The endemic infection rate in HCW was high. HCW adhering to preventive measures in everyday life had lower infection rates. Disclosure of Interests: Manuel Beck: None declared, Alexandra Nieters: None declared, Marta Rizzi: None declared, Ulrich Salzer: None declared, Jens Thiel Speakers bureau: BMS, Nils Venhoff Speakers bureau: Novartis, Nicole Peter: None declared, Hermann Eibel: None declared, Reinhard Voll Speakers bureau: Novartis, Grant/research support from: BMS, Pfizer, Novartis, Stephanie Finzel Speakers bureau: Novartis.
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OBJECTIVES: Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are the most common inflammatory rheumatic diseases (IRD). The aim of this study was to elucidate differences in the outcome of SARS-CoV-2 infection in RA- and SpA-patients. METHODS: Data from the German COVID-19 registry for IRD patients from 30th March to 16th November 2020 were analysed. 208 RA and SpA patients were included in the study, matched for gender and age. RESULTS: 104 SpA patients (40% patients with ankylosing spondylitis, 54% with psoriatic arthritis and 6% with enteropathic arthritis) were compared to 104 RA patients. For both groups, median age was 56 years. TNF-i treatment was reported in 45% of the SpA and in 19% of RA patients (p=0.001). Glucocorticoids were used in 13% of the SpA and in 40% of the RA patients (p=0.001). In both groups, the majority of the patients (97% SpA, 95% RA) recovered from COVID-19. Hospitalisation was needed in 16% of the SpA and in 30% of the RA patients (p=0.05), and oxygen treatment in 10% and 18% respectively (p=ns). Three versus six (p=ns) fatal courses were reported in the SpA versus the RA group. CONCLUSIONS: The study revealed that the hospitalisation rate during COVID-19 infection, but not the mortality, was significantly higher in RA as compared to SpA patients. This could be explained either by different treatment strategies or by different susceptibilities of the two diseases.
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Background:Patients with inflammatory rheumatic diseases (IRD) and infection with SARS-CoV-2 may be at risk to develop a severe course of COVID-19. To gather knowledge about SARS-CoV-2 infections in IRD patients, a national registry was established to elucidate IRD specific profiles of COVID-19.Objectives:To identify risk factors for hospitalisation.Methods:Patients from the German registry on SARS-CoV-2 infection in IRD were analysed. Patients are enrolled with a pre-existing IRD and a positive lab-result for a SARS-CoV-2 infection. The main outcome parameter was hospitalisation versus non-hospitalisation. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Covariates included in the model were age group, gender, key comorbidities (cardiovascular, lung diseases, chronic renal insufficiency), prior and/or current use of glucocorticosteroids (GC) or NSAIDs and remission.Results:Until May 17th, 2020, data from 192 IRD patients with SARS-CoV-2 infection were reported (67 males;124 females;1 diverse). 64 patients were hospitalised, 21 patients were ventilated non-invasively/invasively and 15 patients died.Baseline characteristics are shown in table 1, stratified into the patient groups non-hospitalisation, hospitalisation without ventilation, and hospitalisation with ventilation. Non-hospitalised patients were younger, had less comorbidities and were less often treated with GC. In the group of hospitalised patients compared to non-hospitalised patients more patients were male (42% vs 32% male) with an even higher proportion in the ventilated patient group (57% male).In the multivariable logistic regression model, age65 years (OR 5.1;95%CI 2.3-11.4), cardiovascular comorbidity (OR 2.3;95%CI 1.0-5.0), and prior and/or current treatment with GC (OR 2.6;95%CI 1.2-5.4) were independently associated with hospitalisation.Parameter, N (%)Non-hospitalisation 128 (66.7)Hosp. without ventilation 42 (22.4)Hosp. with ventilation 21 (10.9)Age [years], mean (SD)53.8 (13.4)65.2 (15.5)69.7 (9.9)Female87 (68.5)28 (65.1)9 (42.9)RA60 (46.9)24 (55.8)12 (57.1)Psoriasis23 (18)3 (7)3 (14.3)Axial spondyloarthritis14 (10.9)2 (4.7)0Lupus7 (5.5)1 (2.3)0Remission of IRD67 (52.3)23 (53.5)4 (19)Number of comorbidities, mean (SD)1 (1.2)1.8 (1.4)2.4 (1.5)Cardiovascular disease42 (32.8)25 (58.1)16 (76.2)Pulmonary disease16 (12.5)8 (18.6)8 (38.1)Chronic renal insufficiency5 (3.9)7 (16.3)4 (19)Cancer2 (1.6)4 (9.3)2 (9.5)Obesity (BMI30)23 (18)5 (11.6)3 (14.3)Diabetes3 (2.3)7 (16.3)4 (19)Other comorbidities20 (15.6)9 (20.9)6 (28.6)csDMARD (without HCQ)59 (46.1)25 (58.1)8 (38.1)HCQ13 (10.2)1 (2.3)2 (9.5)bDMARD48 (37.5)15 (34.9)8 (38.1)tsDMARD5 (3.9)1 (2.3)1 (4.8)Glucocorticosteroids47 (37)29 (67.4)13 (61.9)NSAIDs21 (16.4)5 (11.6)1 (4.8)Conclusion:As has been described for COVID-19 in general, also in IRD male gender may be associated with a more severe course of the infection as the descriptive analysis of data shows. Risk factors for SARS-CoV-2 infection-dependent hospitalisation in IRD patients include age (65 years), cardiovascular comorbidities, and prior and/or current treatment with GC.Disclosure of Interests:Anne Regierer Speakers bureau: Novartis, Celgene, Janssen-Cilag, Rebecca Hasseli Grant/research support from: Pfizer, Consultant of: Pfizer, Gilead, Novartis, Celgene, Abbvie, Medac, Bimba Hoyer: None declared, Andreas Krause: None declared, Hanns-Martin Lorenz Grant/research support from: Consultancy and/or speaker fees and/or travel reimbursements: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly. Scientific support and/or educational seminars and/or clinical studies: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, Thermo Fisher., Consultant of: see above, Alexander Pfeil Grant/research support from: This study Investigator Initiated Study “Automatic assessment of jo nt space narrowing in rheumatoid arthritis based on the Post-hoc analysis” (number: IIS-2016-110818) is a part of the of the Investigator Initiated Study “The quantification of inflammatory related periarticular bone loss in certolizumab pegol treated patients with rheumatoid arthritis” (number: IIS-2014-101458) which is supported by UCB Pharma GmbH, Monheim, Germany., Jutta Richter Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Tim Schmeiser Speakers bureau: Actelion, UCB, Pfizer, Christof Specker Consultant of: Abbvie, Boehringer Ingelheim, Chugai, Lilly, Novartis, Sobi, UCB, Celgene, Janssen-Cilag, MSD, Pfizer, Roche, UCB, Toshiba, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Reinhard Voll: None declared, Hendrik Schulze-Koops: None declared, Ulf Müller-Ladner Speakers bureau: Biogen