ABSTRACT
Background: Adapted anti-SARS- CoV- 2 vaccination schedules have been recommended for patients with IMID due to a higher risk of reduced vaccine response. Nonetheless, there is little data on how different vaccine schedules influence immune responses and on the long-term persistence of vaccination responses in this subset. Purpose(s): The aim of this study is to assess the long-term course of humoral responses to SARS-CoV- 2 vaccines in a large prospective cohort of IMID patients and non-IMID controls with up to 10 months of follow-up following the first vaccine dose. Method(s): In February 2020, we started a prospective cohort of IMID patients and healthy controls (HC) to evaluate immune responses to SARS-CoV- 2 vaccines and infection (1). Individuals who provided data starting 4 weeks before their first vaccination and forward were included. Serum anti-SARS- CoV- 2 spike protein IgG were measured by ELISA (EUROIMMUN, Lubeck, Germany) in units of Optical density (OD) at 450 nm. An OD <1.1 was considered as poor response. We used time splines to fit linear mixed-effect models for log-transformed antibody levels and logistic mixed-effects models, adjusting for age and sex to estimate marginal mean antibody levels and adjusted risk of poor response with 95 percent confidence intervals. Antibody levels of twice-vaccinated patients were also compared to those who received 3 vaccinations. Result(s): Between December 2020 and December 2021, 3733 IMID patients and HC contributed 5564 samples, with a median (IQR) follow-up of 23.3 (13.9-0.9) weeks following first immunization (Table 1). By the date of their most recent sampling, 3280 (88%) participants had received two vaccines and 241 (6%) received three. Age and sex-adjusted estimated marginal mean IgG in IMID patients declined after week 10 and were significantly lower at all timepoints compared to controls (Figure 1A, Table 1). Adjusted risk of poor response at week 40 was 2.9% (1.4%-6.1%) in HC whereas 26.1% (15.8-40.0) in IMID (Figure 1B). After a median 20 (10-26). weeks from the second dose, 147 (6%) IMID patients had received a third dose. Adjusted mean antibody levels at 40 weeks in IMID patients who received three vaccine doses were higher than in HC who received two doses (Figure 1C). Conclusion(s): IMID patients had a weaker humoral response to SARS-CoV- 2 vaccination than controls at all time points following the first dose with a high risk of poor response at 40 weeks. Nonetheless, a third dose in IMID patients could provide higher antibody levels compared to unboosted healthy individuals.
ABSTRACT
Background: The frst vaccine against SARS-CoV-2 was approved in December 2020. Immunogenicity of SARS-CoV2 vaccines in patients with immune-mediated infammatory disease (IMID) have so far been evaluated in the 2-6 weeks following complete vaccination and risk groups for poor early vaccine response have been identifed leading to specifc vaccination recommendations. However, data on the long-term course and persistence of vaccine response in IMID patients, as well as the outcomes of the specifc recommendations are lacking. Objectives: To evaluate the long-term course of humoral response to SARS-CoV-2 vaccination in a large prospective cohort of IMID patients and non-IMID controls with a follow-up duration of up-to to 10 months after the frst vaccine dose. Methods: We have initiated a prospective dynamic cohort of IMID patients and healthy controls in February 2020 to monitor immune response to SARS-CoV-2 and respiratory infections including COVID-19 (1). Participants who contributed data starting from the 4 weeks before their frst vaccination onwards were included in this analysis. Antibodies against SARS-CoV-2 spike protein were quantifed with an ELISA from Euroimmun (Lübeck, Germany) with an optical density cutoff of 0.8. We ftted linear mixed-effect models for log-transformed antibody levels using time splines with adjustment for age and sex. Marginal mean antibody levels with 95% confdence intervals (CI) were estimated at selected time points for IMID patients and controls with double vaccination. We descriptively analyzed the observed antibody levels over time in cohort participants receiving two vaccinations vs. three vaccinations. Results: Among 5076 cohort participants, 3147 IMID patients and healthy controls (mean (SD) age 49 (16)) provided 4756 samples for this analysis between December 2020 and 2021, with a median (IQR) 28 (14-31) weeks of follow-up after the frst vaccination (Table 1). 2965 (94%) participants had received at least 2 and 223 (7%) participants had received three vaccine doses by the date of their latest sampling. In IMID patients, age and sex-adjusted estimated marginal mean antibody levels waned after week 16 and were substantially reduced at all time points compared to the controls, fnally dropping to the borderline range (1.01, 95%CI 0.86 to 1.19) at week 40 (Figure 1A, Table 1). A third dose was given to 128 (7%) of IMID patients with a poor response to 2 vaccine doses after a median 20 weeks of the second dose (IQR 10 to 26 weeks). After the third dose, antibody levels in IMID patients were comparable to those of healthy controls at 40 weeks who had three vaccine doses. These were also higher than that of IMID patients and controls who did not receive a third dose (Figure 1B). Conclusion: Humoral response to vaccination against SARS-CoV-2 was weaker in IMID patients compared to controls at all time points after the frst vaccine dose and practically disappeared after 1 year. IMID patients can still achieve a good antibody response with a third dose even after a weak response with two doses.
ABSTRACT
Background: Patients with immune-mediated infammatory diseases (IMID), particularly if treated with B-cell depleting therapies, show reduced humoral responses to SARS-CoV-2 vaccines and increased risk of severe COVID-19 (1,2). Since pre-exposure prophylaxis (PrEP) with monoclonal antibodies against SARS-CoV-2 proved effective in preventing infection and COVID-19 (3) in the general population, PrEP could be used for passive immunization of vaccine-refractory patients with IMIDs. Objectives: To evaluate the persistence of serum and salivary anti-SARS-CoV-2 IgG antibodies in vaccine-refractory patients with IMID after PrEP with casiriv-imab/imdevimab. Secondary outcomes were safety, SARS-CoV-2 infection, and adverse COVID-19 outcomes. Methods: We performed a longitudinal analysis on anti-SARS-CoV-2 IgG titers in IMID patients who received a PrEP with 1200 mg of subcutaneous casirivimab/imdevimab due to high infection risk, as they had not developed an adequate humoral response at least 21 days after three COVID-19 vaccinations (Table 1). Serum and salivary anti-SARS-CoV-2 Spike IgG were quantifed by ELISA (EUROIMMUN, Lübeck, Germany) before PrEP and after 1, 14, and 30 days. IgG levels are given as antibody ratios by dividing the optical density of the sample by that of the calibrator. A cutoff of ≥1.1 was considered positive. Safety as well as polymerase chain reaction (PCR)-confrmed SARS-CoV-2 infection and adverse COVID-19 outcomes (hospitalization, mechanical ventilation, death) after PrEP were recorded. Results: We obtained 92 serum and 75 saliva samples from 26 participants at four consecutive timepoints (Figure 1). Anti-SARS-CoV-2 IgG titers were observed in serum and saliva samples of all participants from day 1 and throughout 30 days after PrEP independently of diagnosis, therapy, total IgG, and peripheral CD19+ B-cells. Serum IgG increased rapidly at day 1 and plateaued from day 14 to 30 (Figure 1A), reaching similar levels as seen in healthy subjects after full vaccination (1), while saliva IgG increased steadily from administration up to day 14 and plateaued at day 30 (Figure 1B). No side effects were reported. Five patients (19.2%) had a close contact with a SARS-CoV-2-infected person, after which all but one remained asymptomatic and with a negative PCR test. The patient who tested positive developed mild COVID-19 with fever and cough. Conclusion: SARS-CoV-2 PrEP induces stable serum and salivary antibody levels in IMID patients who did not respond to COVID-19 vaccination, regardless of pre-existing clinical and serological features. In IMID, PrEP with casiriv-imab/imdevimab is safe and has the potential to prevent infection and severe COVID-19.
ABSTRACT
Background: Digital health applications (DHA) became indispensable patient companions accelerated by the current COVID pandemic [1]. In 2020, for the frst time worldwide, a regulatory framework to reimburse DHA was established in Germany. To get listed as a DHA, preliminary evidence needs to be generated-next to fulflling highest standards in quality and safety. The DHA ABATON RA consists of two parts;1) digital shared-decision-making (SDM) including choosing an appropriate electronic patient reported outcome (ePRO) instrument and the respective ePRO target for the next visit, 2) remote patient monitoring and ePRO tracking by the patient. Hereby, ABATON RA supports a digitally guided Treat-to-Target (T2T) approach. Objectives: The objective of this study is to evaluate a potentially benefcial effect for the patient by using ABATON RA. Methods: Three-armed, partially blinded multicenter trial (RCT) including RA patients who regularly use a smartphone. Patients attend 3 visits, 3 months apart (T0, T3, T6), with one follow-up visit (T9). Intervention group (IG): Patients use ABATON RA. Via SDM patients and rheumatologists choose a specifc ePRO and respective treatment target for the next visit in three months, e.g. RAID ≤4. Control group (CG): Standard of care treatment (no DHA). Placebo group (PG): Usage of a placebo version of ABATON RA providing only Regensburger Insomnie Skala (RIS) and Epworth Sleepiness Scale (ESS) as ePROs. No SDM is conducted and ePRO results are not presented to HCP. Results: This interim analysis evaluated the frst 38 patients that completed T3. IG: 13 patients (Av. age 55.9, 61.5% females);PG: 12 (Av. age 50.7, 66.7% females);CG: 13 (Av. age 56.1, 76.9% females). We observe a signifcant improvement in the mean over time in a pairwise comparison within the intervention group for the following: Pt-GA mean difference of 2.98 (p = 0.025, partial η2 = 0.353), pain mean difference of 1.46 (p = 0.049, partial η2 = 0.286) whereas all pairwise comparisons for the two parameters were non-signifcant in PG and CG. The patient reactions assessment (PRA) score, measuring patient perceived quality of the patient-provider relationship, increased by a mean of 4.15 points in IG, compared to a slight decrease of 1.92 for PG and 2.77 for CG. Conclusion: These preliminary fndings show benefcial differences among the groups in favor of IG: 1) for quality of life and 2) the physician-patient-relationship. A digitally enhanced therapy is non-inferior to the gold-standard of exclusive in-person treatment. Patients seem willing and able to get involved in an enhanced treat-to-target and shared decision-making approach.
ABSTRACT
Background: The ongoing COVID-19 pandemic has disrupted face-to-face teaching of medical students and forced efforts in finding alternative approaches. In order to help maintain high-quality education, a new virtual reality (VR)-based concept for training medical students in rheumatic and musculoskeletal diseases (RMD) has been developed. This VR training concept is based on the integration of real patient data with two-and three-dimensional visualized pathological joints from X-ray and computed tomography generated images. Objectives: To evaluate the practicability and acceptance of the VR training application in the digital curricular education of medical students during the COVID-19 pandemic. Methods: A short refresher lecture on rheumatic diseases (duration 60 minutes) was followed by presenting the VR training concept to the students. The VR training concept included the demonstration of three virtual patients with early rheumatoid arthritis, rheumatoid arthritis psoriatic arthritis regarding the symptoms, current medical problems, disease patterns at the imaging (conventional radiographs and high-resolution computed tomography) and therapy options. The practicability and acceptance of the VR was evaluated by medical students using a survey. Results: The study encompassed 237 medical students (163 female, 73 male, one diverse, age range 20 to 40 years). 72 % of the participants rated the virtual teaching as good or very good. 87 % presented an expanded knowledge for rheumatoid arthritis and psoriatic arthritis through the VR. Moreover, 91 % reported that the lecture provided a deeper understanding of RMD. Furthermore, 60 % of the students asked for additional courses by VR. Conclusion: The study highlighted the usefulness of innovative VR tools for teaching medical students digitally about RMD. VR applications can be a complementary educational modality for medical students, especially during the COVID-19 pandemic, to provide students with the best possible clinical experience while ensuring that patient, student, and staff safety is not compromised.