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BackgroundTreatment with Rituximab (RTX) in patients with rheumatic diseases (RD) has presented a challenge during the COVID-19 pandemic, as RTX leads to markedly reduced and often undetectable antibody responses after COVID-19 vaccination (1).ObjectivesTo investigate the effect of COVID-19 mRNA revaccination (two doses) on the antibody response in patients with RD who were initial vaccine non-responders. Further, to examine if B-cell levels or T-cell responses before revaccination predicted seroconversion.MethodsFrom a RD cohort (COPANARD) vaccinated with the standard two-dose COVID-19 vaccinations, we enrolled cases without detectable antibody responses (n=17) and controls with detectable antibody response (n=29). Blood donors (n=32) were included as additional controls. Samples were collected before and six weeks after completed revaccination. Total antibodies (abs) and specific IgG, IgA, and IgM against SARS-CoV-2 spike protein, SARS-CoV-2 neutralizing abs, and SARS-CoV-2 reacting CD4+ and CD8+ T-cells were measured before and after revaccination. B-cells (CD19+CD45+) were quantified before revaccination. This study was funded by the Danish Rheumatism Association.ResultsPatient demographics are given in Table 1. Forty-seven percent of cases had detectable total SARS-CoV-2 abs and neutralizing abs after revaccination. However, antibody levels were significantly lower than in controls and blood donors (p<0.008), Figure 1A+B. Revaccination induced an antibody class switch in cases with a decrease in detectable IgM abs (Baseline 11/17, Followup 3/17) and increase in IgG. No significant difference was observed in T-cell responses before and after revaccination between the three groups, Figure 1C. The proportion of cases with detectable CD4+ T cells increased from 69% to 88% (p=0.25), and for CD8+ T cells, the proportion decreased from 88% to 82% (p=1.00). Only 29% of cases had measurable B-cells compared to 100% of controls and blood donors, Figure 1D. Fifty percent of revaccinated cases who seroconverted had measurable B-cells before revaccination, Figure 1D.Univariate logistic regression analysis was performed to analyze if active RTX treatment, the presence of B-cells, or a positive T-cell response prior to revaccination predicted seroconversion of total SARS-CoV-2-abs in the patient cohort. We did not find a significant explanatory effect of either variable in the univariate logistic models, data not shown.Table 1.DemographicsCases Revaccination, n=17Controls Boost, n=29Female sex, no(%)1482%2172%Age, median (IQR)6549 - 706762 - 72Disease duration, years1510 - 18229 - 31Rheumatoid Arthritis/SLE13/410/19None DMARD529%828%Prednisone424%13%Methotrexate741%1241%Hydroxychloroquine212%414%None biologic treatment424%931%Rituximab1271%0TNF-inhibitors16%724%JAK-inhibitors0621%IL-6-inhibitors, Abatacept, Benlysta0724%Previous rituximab treatmentAny rituximab treatment1694%13%RTX within the last 15 months, no1488%0Cumulative total dose, mg134-242Time from RTX to revaccination, months95-1249Figure 1.ConclusionIn conclusion, forty-seven percent of initial non-responders were able to seroconvert after two-dose revaccination. However, plasma concentrations of the antibodies against SARS-COV-2 and the levels of neutralizing capacity remained significantly lower than in immunocompetent blood donors. B-cell levels or T-cell responses before revaccination did not predict seroconversion. Our study suggests that patients with RDs who did not mount a detectable serological response to a COVID-19 mRNA vaccine have a T cell response similar to immunocompetent controls. Future studies should establish the antibody levels that identify RD patients without sufficient protection against SARS-CoV-2 infection.References[1]Troldborg A, et al. Time Since Rituximab Treatment Is Essential for Developing a Humoral Response to COVID-19 mRNA Vaccines in Patients With Rheumatic Diseases. J Rheumatol. 2022.AcknowledgementsThe Danish Rheumatism Association [grant number R203-A7217]. We acknowledge all patients and blood donors contributing to the stud for their invaluable participation. The authors would like to thank Sif Kaas Nielsen and Mads Engelhardt Knudsen, the Laboratory of Molecular Medicine at Rigshospitalet, for their excellent technical assistance in analyzing the samples.Disclosure of InterestsNone Declared.
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Background: The severe, acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), leading to coronavirus-19 (COVID-19), was detected for the first time in Wuhan, China in December 2019. In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the MM-related immunodeficiency (Glenthøj, A et al. PMID: 32939853). To some extent, the COVID-19 pandemic has changed standard of care towards extended use of oral regimens and limiting hospital visits (Terpos E et al.PMID: 32444866). We aimed to investigate the quality of life (QoL) of Danish patients with MM during the COVID-19 pandemic. We hypothesized that patients living alone and those under the age of 65 years, as a consequence of the pandemic, would experience impaired QoL due to social isolation and fear of infection with SARS-CoV-2. Methods: The Danish prospective, nation-wide, observational survey “Quality of life in Danish patients with multiple myeloma” (QoL-MM) (Nielsen LK et al. PMID: 30656677) framed our study. In QoL-MM, survey data are obtained at enrolment and subsequently at 12 follow-up time points over a two-year period. The following PRO questionnaires are used;the cancer-generic instrument of European Organisation for Research and Treatment of Cancer Quality of life (EORTC) QLQ-C30 (EORTC QLQ-C30), the Multiple Myeloma module QLQ-MY20 (EORTC QLQ-MY20), the Chemotherapy-Induced Peripheral Neuropathy module (EORTC QLQ-CIPN20) and the Short-form health survey version 2 (SF12v2). In the present study, a subpopulation of the QoL-MM cohort was constructed, based on the response time of the questionnaires. QoL was compared using patient-reported outcome (PRO) data obtained before and during the COVID-19 pandemic at group level. In a Danish context, first wave was defined as April to June 2020 and the second wave as November 2020 to January 2021. The QoL data were analyzed using mixed effects linear regression, with a year-period-interaction. Pre-COVID versus COVID mean domain score difference was considered evident, if the difference was both statistically significant (p-value <0.05) and clinically relevant, using minimal important difference (MID) defined as 0.3 standard deviation of the mean score. Results: The study included 616 patients (63% newly diagnosed and 37% relapsed) with a mean age of 68.2 years (standard deviation, 9.2);40% were females;76% were married/cohabiting, and 24% single. Questionnaire completion rates during the investigated periods were between 96% and 97%. In total, 1,685 completed sets of questionnaires were included in the analyses. The patients reported no statistically significant and clinically relevant difference in QoL during the first and second waves of the COVID-19 pandemic, compared to one year earlier, see table 1. When analyzing the subpopulations, we found that patients below 65 years reported improved physical health summaries (p-value 0.016), decreased fatigue (p-value < 0.001), less insomnia (p-value 0.002) and improved role functioning (p-value <0.001) during the first wave, reaching both statistical significance and the threshold of MID. The group of patients living alone reported improved role functioning during the first wave, reaching both statistical significance (p-value <0.001) and the threshold of MID. These findings were not evident during the second wave, see table 1. Conclusion: As a group, Danish patients with MM did not report impaired QoL during the COVID-19 pandemic. In contrary, we observed improvements in some domains in patients below 65 years. Our observations indicate that the patients with MM have felt cared for and in good hands during the first and second waves of the COVID-19 pandemic. However, part of the reason for our finding of no negative impact on QoL by the pandemic could be that the questionnaires used were not developed to capture the impact of the pandemi on QoL. Importantly, our results suggest that QoL data collected in clinical trials during the pandemic allow interpretation without adjusting for the impact of the pandemic. [Formula presented] Disclosures: Redder: Janssen-Ciliag: Research Funding. Frederiksen: Alexion: Research Funding;Gilead: Research Funding;Abbvie: Research Funding;Janssen Pharmaceuticals: Research Funding;Novartis: Research Funding. https://www.qualitymetric.com/health-surveys/the-sf-12v2-pro-health-survey/
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This paper describes a one-day INTERACT 2021 workshop on remote testing with users as participants. Remote user testing has been around since the mid-nineties, but the Covid-19 pandemic has boosted the interest in remote working in general and thus also remote testing. The workshop aim is to present and discuss the current state-of-the-art of remote testing methods and identify emerging trends. Subjects that will be discussed include, but are not restricted to: Remote testing methods and platforms;capturing of quantitative as well as qualitative data;moderated, unmoderated and remotely moderated tests;testing of physical products;and remote testing of participants with special needs. © 2021, IFIP International Federation for Information Processing.
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Background: In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected for the first time in Wuhan, China, causing the coronavirus disease 2019 (COVID-19). Mortality rate in patients with multiple myeloma (MM) hospitalized due to COVID-19 has been reported to be 50% higher compared to non-cancer patients. The COVID-19 pandemic has resulted in adaption of myeloma care recommendations including key principles of limiting hospital visits by use of telemedicine communication and to use oral agents as much as possible and/or allowing treatment breaks. To mitigate the risk of COVID-19 spreading, extensive national lockdowns have been practiced and patients and caregivers have been encouraged to practice social distancing. Aims: The aim was to investigate the impact of the first and second wave of the COVID-19 pandemic on quality of life (QoL) in Danish patients with MM. Methods: The study was designed as a cross-sectional study comparing QoL in patients with MM using data obtained the year before the pandemic (pre-COVID) as a reference in comparison to the COVID period. In a Danish context, first wave was defined as April to June 2020 and the second wave as November 2020 to January 2021. The survey data originates from an ongoing cohort study, "Quality of life in Danish Multiple Myeloma patients" (QoL-MM), which is a Danish prospective, nationwide, observational survey, initiated in February 2017. Survey data are obtained at enrolment and subsequently at 12 follow-up time points over a two-year period including 24 QoL domains assessed by the European Organisation for Research and Treatment of Cancer Quality of life QLQC30, the Multiple Myeloma module QLQ-MY20, the Chemotherapy- Induced Peripheral Neuropathy module and the Short-form health survey version 2. The QoL data was analysed using mixed effects linear regression, with a year-period-interaction. Pre-COVID versus COVID mean domain score difference was considered evident, if the difference was both statistically significant (p-value <0.05) and clinical relevant using minimal important difference defined as 0.3 standard deviation of the mean score of all included 2019 answers. For data validation, the mean scores of the pre-COVID period were compared to the mean scores for 2018. Results: In the study, 616 patients was included (63% newly diagnosed and 37% relapsed) with a mean age of 68.2 years (standard deviation 9.2). Females represent 40% of the population. Seventy-six percent were married/ cohabiting, 24% single. The completion rates during the investigated periods were between 94% to 97%, and a total of 2,576 completed sets of questionnaires were included in the analyses. The Danish MM patients reported no statistical significant and clinical relevant difference in QoL during the first or second wave of the COVID-19 pandemic compared to one year earlier. Summary/Conclusion: Patients with MM infected by COVID-19 are in increased risk of dying and the pandemic has to some extent affected the usual clinical care program and caused restrictions in their everyday living. However, the pandemic does not seem to impact the patients′ reporting's of QoL. A limitation, however, may be that the questionnaires used are not validated to capture psychosocial health during a pandemic. Still, our results is important as it documents that QoL collected in clinical trials during the pandemic allow interpretation without adjusting for the impacts of the pandemic.
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Purpose: Exercise therapy in combination with education is recommended as first-line treatment for painful knee osteoarthritis (KOA). In clinical practice, supervised exercise therapy and education demonstrate approx. 25% pain relief following an 8-week treatment program. Studies indicate that some patients with KOA experience larger pain relief compared to others. Assessments of peripheral and central pain mechanisms has been used to predict responders and non-responders to treatment. Studies on surgery and treatment with non-steroid anti-inflammatory drugs in patients with KOA have indicated that patients with higher levels of pain sensitivity might respond less positive. The primary aim of this observational study was to investigative if measures of pre-treatment pain sensitivity was associated with clinical outcomes after supervised exercise therapy and education. Methods: Patients with painful KOA (numeric rating scale [NRS, 0-10] ≥ 3) were included, and examined before and 1-2 weeks after 6-8 weeks of supervised exercise therapy (2 sessions of 1 hour per week) and 2 sessions of patient education. Handheld pressure pain threshold (PPT) was assessed locally at the most painful knee at 4 peripatellar sites (knee) and at two remote sites at the m. tibialis anterior (TA) and the contralateral m. extensor carpi radialis longus (ECRL). Further, computer-controlled cuff algometry at the lower leg with the most intense knee pain was used to assess pain detection threshold (cPDT), pain tolerance threshold (cPTT) and conditioned pain modulation (cCPM). Peak pain intensity within the last 24 hours (NRS, 0-10), PainDetect questionnaire (PDQ, 0-38) and Knee injury and Osteoarthritis Outcome Score (KOOS) were assessed as clinical measures. PDQ assesses the pain phenotype with a score ≤ 12 indicating probably nociceptive pain, 13-18 uncertain pain phenotype and ≥ 19 probably neuropathic pain. KOOS4 was defined as the average score of the subscale scores for Pain, Symptoms, Activity of Daily Living and Quality of Life (0-100 with 0 indicating extreme problems and 100 indicating no problems). Physical performance was assessed using the 40-meter walk test (40MWT). A treatment attendance score (%) was calculated for each patient by dividing the number of sessions attended by the number of sessions scheduled (twice per week). This study was approved by the local ethical committee (N-20190045) and pre-registered at (NCT04123756). All participants gave oral and written informed consent prior to enrollment. Results: This interim analysis reports on the first patients recruited for this observational study. Eleven KOA patients (6 women) with mean peak pain intensity of 6.0 ± 1.5, median pain duration 17.0 months (range: 5-120) and body mass index of 30.3 ± 5.7 were included in this interim analysis. In one subject, follow-up was made by telephone due to the COVID-19 situation, leaving 10 subject for the analysis on changes in pain sensitivity measures. Attendance score was 98.1 ± 18.1% during 7.1 ± 0.7 weeks. Following treatment, improvements were observed in KOOS4 (57.1 ± 10.0 at baseline vs. 65.3 ± 13.1 at follow-up, P < 0.01), and peak pain intensity (6.0 ± 1.5 vs. 3.2 ± 2.3, P < 0.001). No differences were seen for PDQ (7.6 ± 2.6 vs 6.8 ± 3.6, P = 0.77) and 40MWT (27.1 ± 6.6 sec vs. 25.8 ± 5.2 sec, P = 0.29). Further, no changes in any of the pain sensitivity measures were found following treatment (all Ps > 0.15). Pre-treatment cPDT (rs < 0.73, P < 0.05) and cPTT (rs < 0.72, P < 0.05) were associated with post-treatment KOOS4. No significant associations were found between pre-treatment PPT or CPM effects and post-treatment peak pain measures or change in KOOS-4 (P > 0.05). Conclusions: These results indicate that patients with higher pre-treatment pressure pain sensitivity have worse KOOS4 scores following supervised exercise therapy and education.