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BackgroundThe COVID-19 pandemic caused concerns whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease modifying drugs (DMARDs) and/or prednisolone exhibit an adequate immune response to the applied SARS-CoV2 vaccines.ObjectivesWe established the DECODIR study to assess and compare the efficacy of the SARS-CoV2 vaccines administered as part of the national vaccine roll-out: BNT162b2 vaccine (Pfizer/BioNTech) and mRNA-1273 vaccine (Moderna). The vaccines were offered as two doses four weeks apart;followed by a booster vaccination six months later. This national regimen included inflammatory rheumatic patients regardless of their respective anti-inflammatory treatment. We used patients' SARS-CoV2 IgG serum level as proxy for vaccination response (1).MethodsThe study was conducted as a longitudinal prospective cohort study. Patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA) or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg, and monitored in the Danish DANBIO registry, were included.Blood samples, Disease activity and treatment information (cs/bDMARD, prednisolone) were collected at baseline (i.e. prior to vaccination), after six weeks, six and twelve months. SARS-CoV-2 IgG levels in serum were assessed by ELISA (Thermo-Fischer), and manufacturer's cut-off (>=10 EliA U/mL) selected as definition of sufficient IgG response. Antibody response was measured and compared at all four time points.Associations between antibody response, age, gender, disease (RA/PsA/SpA), treatment (none, cs/bDMARD or prednisolone) and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR) and bootstrapped 95% confidence interval (CI) of the median.ResultsA total of 243 patients were included at baseline and all were followed-up after six weeks;data from 233 patients were available at six months and for 229 patients at twelve months' follow-up. Those 229 patients had completed the national vaccination programme.The measurements performed 6 months after baseline demonstrated a per se decrease of IgG levels for the whole study population (median of 2.08 EliA U/mL at 6 months vs. 16 EliA U/mL at 6 weeks). The final measurements performed after twelve months demonstrated a significant increase of IgG levels. Thus, the completed vaccination programme, was followed by a significant increase in IgG levels (median of 100 EliA U/mL at twelve months vs. 16.5 EliA U/mL at six months, p < 0.001).Sufficient response rates were now recorded in all treatment scenarios, also in patients treated with prednisolone or combination of csDMARD and bDMARD. These two groups were at 6 months characterized by significant lower response rates, when compared with patients without any DMARD treatment.ConclusionCompleted vaccination programme defined as two doses plus booster vaccination resulted in a sufficient vaccination response as measured by IgG levels regardless of RA treatment.It is noteworthy that IgG levels increased markedly in patients treated with a combination of cs/bDMARD or oral prednisolone, who had low IgG levels (below manufacturer's cut-off >=10 EliA U/mL) after 6 months. Our results strongly support the efficacy of the complete vaccination programme including the 3rd booster vaccine in patients with inflammatory rheumatic diseases.Figure 1.Serum IgG-levels at baseline, 6 weeks, 6 months and 12 months;stratified by antirheumatic treatment. (Box plot showing median and interquartile range).[Figure omitted. See PDF]Reference[1]Schreiber K. et al. Reduced Humoral Response of SARS-CoV-2 Antibodies following Vaccination in Patients with Inflammatory Rheumatic Diseases— an Interim Report from a Danish Prospective Cohort Study. Vaccines 2022, 10(1), 35;https://doi.org/10.3390/vaccines10010035AcknowledgementsWe acknowledge all patients contributing to the DANBIO registry.The Danish Rheumatologic Biobank is a knowledged for handling and storage of biological material.Lab chieftechnician Charlotte Drachmann is acknowledged for her assistance.Disclosure of InterestsChristine Graversgaard: None declared, Karen Schreiber Speakers bureau: Lilly, UCB, Henning Jakobsen: None declared, Randi Petersen: None declared, Anders Bo Bojesen: None declared, Niels Steen Krogh: None declared, Bente Glintborg Grant/research support from: Pfizer, AbbVie, BMS, Sandoz, Merete Lund Hetland: None declared, Oliver Hendricks Speakers bureau: Pfizer, Lilly, Novartis.
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Background:COVID-19 vaccine hesitancy among pregnant and breastfeeding women with autoimmune diseases (AID) is often attributed to the fear of adverse events (AE) and disease flares (DF). No data are available regarding COVID-19 vaccine safety in this population.Objectives:We aimed at describing delayed-onset (>7 days) vaccine-related AE (minor and major), DF, and related AID treatment modifications from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.Methods:Among complete responses from 9201 participants as of June 21, 2022, 6787 (73.8%) were women. Six subgroups were identified upon diagnosis of AID vs healthy controls (HC) and their pregnancy/breastfeeding status at the time of any dose of vaccine (Figure 1).Figure 1.Flowchart of the study. AID: autoimmune diseases;HC: healthy controls;rAID: rheumatic AID;nrAID: non-rheumatic AID.[Figure omitted. See PDF]ResultsForty pregnant and 52 breastfeeding AID patients were identified and their vaccination rates (at least one dose) was 100% and 96.2%, respectively (Table 1). Overall AE, minor AE, and major AE were reported significantly more frequently by pregnant than non-pregnant patients (45% vs. 26%, p=0.01;40% vs. 25.9%, p=0.03;17.5% vs. 4.6%, p<0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18% of age- and disease-matched control patients (n=2315). All DF in pregnant/breastfeeding patients were managed with glucocorticoids and a fifth of them required initiation or change in immunosuppressive treatment.Table 1.Characteristics of female subjects according to groups. Percentages in parenthesis. *Pregnancy/breastfeeding status at the time of the survey and/or at the time of at least one dose of COVID-19 vaccine. Chi squared test: ~ p=0.01;° p=0.03;§ p<0.01.Total Women (n=6787)Group A Non-pregnant, non-breastfeeding with AID (n=4862)Group B Pregnant with AID* (n=40)Group C Breastfeeding with AID* (n=52)Group D Non-pregnant, non-breastfeeding HC (n=1749)Group E Pregnant HC* (n=31)Group F Breastfeeding HC* (n=53)Age (median, IQR)47, 35-5850, 38-6134, 31-35.2533, 30-3539, 29-4934, 30-36.533, 30-36Caucasian3225 (47.5)2634 (54.1)12 (30)22 (42.3)538 (30.8)7 (22.6)12 (22.6)No comorbidities3027 (44.6)1815 (37.3)19 (47.5)36 (69.2)1102 (63)17 (54.8)38 (71.7)Number of vaccinated women, n (%)6632 (97.7)4753 (97.8)40 (100)50 (96.2)1710 (97.8)30 (96.8)49 (92.5)≥3 doses4850 (71.5%)3583 (73.7%)26 (65%)33 (63.5%)1155 (66%)23 (74.2%)30 (56.6%)No AE4950 (74.6)3517 (74)~22 (55)~36 (72)1312 (76.7)22 (73.3)36 (73.5)Injection site (arm) pain and soreness630 (9.5)471 (9.9)7 (17.5)7 (14)138 (8.1)2 (6.7)5 (10.2)Minor AE1614 (24.3)1232 (25.9)°16 (40)°12 (24)338 (19.8)7 (23.3)10 (20.4)Major AE285 (4.3)196 (4.6)§7 (17.5)§1 (2)77 (4.5)1 (3.3)3 (6.1)Hospitalization74 (1.1)51 (1.1)2 (5)0 (0)20 (1.2)0 (0)1 (2)ConclusionThis study provides the first insights into the safety of COVID-19 vaccination during the antenatal period in women with AID. While AEs were more commonly reported by pregnant patients with AID, these were no higher than among pregnant healthy controls without AID. These observations are reassuring, likely to strengthen physician-patient communication and overcome hesitancy as the benefits for the mother and fetus by passive immunization are likely to overweigh the potential risks of AE and DF.Reference[1]Fazal ZZ, et al;COVAD Study Group. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int 2022;42:2151-2158.AcknowledgementsThe authors are grateful to all respondents, to all patients support groups, and to all COVAD Study Group collaborators from 106 Countries.Disclosure of InterestsNone Declared.
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Background: During the COVID-19 pandemic, it remains a major concern whether patients with rheumatic musculoskeletal disease treated with conventional (cs) or biologic (b) disease modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV2 vaccines. There remains an urgent need for more data on SARS-CoV-2 vaccine efficacy to inform healthcare providers on the efficiency of the applied vaccination, potential need of and period for booster and/or re-vaccination. Objectives: To assess and compare the efficacy of the SARS-CoV2 vaccines BNT162b2 vaccine (Pfzer/BioNTech) and mRNA-1273 vaccine (Moderna). (The vaccines were administered as part of the Danish vaccine roll out and offered each with two doses and approximately four weeks apart). Patients' SARS-CoV2 IgG serum level was used as proxy to determine vaccination response. Methods: We established the 'Detection of SARS-CoV2 antibodies in Danish Infammatory Rheumatic Outpatients' study (DECODIR) as a longitudinal prospective cohort study. Patients with rheumatoid arthritis (RA), spondyloarthrop-athies (SpA) or psoriatic arthritis (PsA) receiving their outpatient treatment and monitored in the Danish DANBIO registry at the Danish Hospital for Rheumatic Diseases (DG), Sonderborg were included (April-June 2021). Bloods, patient reported outcome measurements (PROMS), clinical data and treatment information (cs/bDMARD) were collected at baseline (prior to vaccination) and after six weeks and six months. SARS-CoV2 IgG levels in serum were assessed by ELISA (ThermoFischer), and manufacturer's cut-off (>=10 EliA U/mL) selected as defnition of sufficient IgG response. Associations between antibody response, age, gender, disease (RA/PsA/SpA), treatment with no or cs/bDMARDs and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR) and bootstrapped 95% confdence interval (CI) of the median. Results: A total of 243 patients were included at baseline and after six weeks;at six months' follow-up data were available for 233 patients. After six weeks, vaccination was followed by a signifcant increase in IgG levels (median of <0.7 EliA U/mL at baseline versus 36.5 EliA U/mL). Patients treated with a combination of both cDMARD and bDMARD had signifcantly lower IgG levels compared to patients without any DMARD treatment (8,2 EliA U/mL vs 19.5 EliA U/mL (p<0.001)). Patients treated with oral prednisolone (any dose) also showed signifcantly lower median IgG levels compared to patients without DMARD treatment (3,8 EliA U/mL vs 19.5 EliA U/mL (p<0.01)). The actual measurements six months after baseline demonstrated a signifcant decrease of IgG levels for the whole study population (median of 16 EliA U/mL at six month vs 36.5 EliA U/mL at six weeks, p < 0.001) (Figure 1). Similar to week 6, lowest response rates were found in patients treated with prednisolone or combination of csDMARD and bDMARD. After 6 months, the proportional odds model revealed signifcantly lower median IgG antibody level in patients who received Pfzer compared to Moderna (median 15 EliA U/mL (95%CI: 13-18) vs 44.5 EliA U/mL (95%CI: 36-83) (p<0.001). Conclusion: IgG levels decreased markedly six months after the initial double dose regimen. Patients treated with a combination of cs/bDMARD or oral pred-nisolone are at higher risk of inadequate vaccine response as measured by IgG level. Our results support the decision for the need of a third booster vaccine in patients with infammatory rheumatic diseases, especially in the case of cs/bDMARD combination treatment and prednisolone. The data may indicate a need for further revaccination in these patients.
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Background: People with infammatory arthritis (IA) treated with conventional or biological immunosuppressive disease-modifying anti rheumatic drugs (DMARDs), were initially considered to have an increased risk of severe illness from SARS-CoV-19 (COVID-19) infection compared to the general population. Although resent studies have not confrmed this, people with IA have reported high level of anxiety and self-isolation during the pandemic (1). Only few studies have qualitatively explored how people with IA experience the impact the COVID-19 pandemic and the SARS-CoV-19 vaccinations. Objectives: To explore how people with IA experienced restrictions during the COVID-19 pandemic and the possible impact of vaccination on their protection against COVID-19 and their everyday lives. Methods: Semi-structured in-depth interviews were conducted via telephone or video with 19 people with IA in May-August 2021, shortly after they were enrolled in the national COVID-19 vaccination programme (all Danish citizens >18 years of age invited for SARS-CoV-19 vaccination, free of charge, with timing depending on age and comorbidities). At the same time, society gradually reopened after a complete lock-down. Qualitative content analysis, inspired by Graneheim and Lundman (2), was applied to analyse the data. Two patient research partners were involved in development of the study protocol, an interview guide and in the interpretation of fndings. Results: The participants' age ranged from 21 to 64 years, median 50 years. 7 male and 12 female, all diagnosed with IA (Psoriatic arthritis n=4, Axial Spondyloarthropathy n=4, Rheumatoid arthritis n=9, and Juvenile arthritis n=2) and 14 were treated with DMARDs. Two had not accepted vaccination. The analysis derived five themes: 1: 'Changing and divergent information'. The participants experienced there was an overload of general information to the public, while targeted information on the specific risk for people with IA was lacking;2: 'Individual interpretation of own risk', refilecting that participants had to find their own level of daily-life restrictions, a task they found to be very difficult;3: 'Impact on everyday life'. They took self-imposed precautions to protect themselves and their families from attracting COVID-19;4: 'Position in society and the vaccination programme', emphasizing that participants were affected by the inconsistent announcements from authorities whether they were considered to be in particular risk or not, and some expressed concerns regarding the DMARDs influence on the effect of the vaccine and 5: 'Reopening is somehow harder than lock down'. A societal spirit of being 'in this together' emerged through the lock-down and some were concerned that fewer restrictions during reopening of the society would put them in higher risk of a COVID-19 infection and force them to continue self-isolation. Conclusion: The COVID-19 pandemic affected the everyday lives of people with IA due to the authorities' restrictions and further self-imposed precautions throughout lock down and reopening of society. People with IA experienced a lack of consistent information and felt alone to assess their own SARS-Cov-19 infection risk.
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Methods: Participants (N=30) 40-60 years old, yoga-naïve, and relatively sedentary, were recruited during 2020-2021. During visit 1, a baseline blood sample was drawn before each participant was randomized into 3-groups (intense or mild stretching or control). Both stretching groups received a one-on-one 1-hour yogic stretching session;stretching was supported by props (blocks and mats), and sessions were video-recorded. After the intervention, 6 blood samples were obtained at different time points (0-, 30-, 60-, 120-, 180- minutes, and 24h). Cytokine levels were quantified using a human inflammation antibodies panel and flow cytometry. Due to the study's pilot nature, analyses focused on descriptive statistics and exploratory analyses for Area Under the Curve (AUC), generalized linear mixed models to characterize longitudinal patterns of cytokines, and Pearson correlations. Results: We observed that it was feasible to recruit participants, and collect and analyze blood samples even during the COVID-19 pandemic;no adverse events were reported. The recruitment process took 11 months;97% of participants completed two study visits, and 88% adhered to the yogic stretching protocol. Our preliminary results identified 8 cytokines that were the most informative when comparing the AUC between groups. At the same time, our correlation analysis identified 7 cytokines (e.g., IL-6) that were the most informative when comparing delta correlations from baseline to the first timepoint post-intervention. Background: To conduct a pilot feasibility three-arm-RCT to gather preliminary data on the impact of an acute yogic stretching intervention on the dynamics of circulating inflammatory cytokines in healthy yoga-naïve participants. Conclusion: It was feasible to measure the systemic effect of an acute intervention of yogic stretching on the short-term dynamics of inflammatory cytokines. Results provide valuable information for informing the future design of a fully powered study.
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Individuals experience variable degrees of severity and interference from chronic pain. While clinical diagnosis and pain symptomology may importantly inform treatment options, person-level characteristics may also impact treatment efficacy. The biopsychosocial model of pain includes several pain-modulatory factors which may inform meaningful categorization, or clustering, of individuals with chronic pain, and help predict pain outcomes. In this observational, longitudinal study conducted approximately shortly after the onset of social distancing, patients with chronic pain (N=94) completed validated assessments of known psychosocial (depression, stress, sleep, catastrophizing) pain modulators and pain intensity, which were used to empirically cluster patients into 3 groups using a two-step hierarchical approach. Subsequently, at 1 year later, degree of pain interference, loneliness, social support, mindfulness, and optimism were compared between these 3 groups using ANOVAs. Participants clustered empirically into three groups: 1) Global Elevation Symptoms (GES), characterized by high psychological distress and moderate pain intensity;2) Pain Intensity Predominant (PIP), characterized by high pain intensity, but average psychological distress;and 3) Less Elevated Symptoms (LES), characterized by low pain intensity and psychological distress. At the 1-year follow-up, patients in the GES cluster reported significantly greater pain interference than the other two clusters, as well as greater feelings of loneliness and lower mindfulness and optimism compared to the LES cluster. This study supports prior research suggesting that psychosocial-based clustering of patients can be used to identify distinct groups of chronic pain patients. In particular, patients identified as belonging to the GES cluster (high psychological distress, high pain intensity early after onset of social distancing) were at greater risk of suffering from pain a year later, as well as loneliness and less mindfulness and optimism. Patient clustering techniques may help identify high risk patients and suggest behavioral interventions to improve pain by addressing psychosocial modulators of pain. Grant support from 5R35GM128691-02.
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The COVID-19 pandemic social distancing mandates have increased levels of social isolation, a change which appears to have impacted some chronic pain patients more than others. Previous research suggests that feelings of loneliness and sleep disturbance may importantly modulate pain. In the present study, we examined whether the personality trait of introversion served as a protective factor against worsening pain interference during conditions of social isolation, and whether this was related to differences in sleep disturbance and loneliness. Chronic pain patients in Massachusetts (n=150) completed electronic questionnaires 4-8 weeks after the state-wide social distancing mandate. Validated questionnaires included the Brief Pain Inventory (BPI), Myers-Briggs introversion/extroversion subscale (1-10), UCLA Loneliness and PROMIS Sleep Disturbance short forms. Change scores were calculated by subtracting recalled scores from current scores. Linear regression was used to assess association between factors, and mediation analyses were used to assess the degree to which other factors mediated the relationship between introversion and change in pain interference. Introversion scores were inversely related to increased pain interference since social distancing (Rho=-0.194, p=0.017), such that patients with higher introversion scores showed little to no change in pain interference, compared to more extroverted patients. Higher introversion was also associated with lower increases in sleep disturbance (Rho=-0.163, p=0.046) and loneliness (Rho=-0.279, p=0.001) since social distancing. Multiple simple mediation analyses revealed that the relationship between introversion and change in pain interference was partially mediated by differential changes in sleep disturbance and loneliness. Chronic pain patients experience varying degrees of worsening of pain interference with social distancing, which may be partially explained by their degree of introversion/extroversion. In particular, more introverted patients appeared to be partially protected, experiencing less of an increase in loneliness and sleep disturbance and, in turn, less of an increase in pain interference. 5R35GM128691-02.