ABSTRACT
Background: SARS-CoV-2 antibody responses after COVID-19 vaccination are attenuated in people living with MS on high efficacy DMTs such as Fingolimod and Ocrelizumab. Uncertainties on how to manage vaccination schedule and DMT administration persist. Furthermore, data on effects of newer related DMTs like Siponimod and Ofatumumab are limited. Objective(s): We aimed to determine the seroprevalance of Spike antibody and the longevity of antibody mediatedimmune protection after COVID-19 vaccination in MS patients. Method(s): Spike IgG antibodies against Wuhan SARS CoV-2 were assessed in sera (n=520) of MS patients collected pre-vaccination (baseline n= 304), 1 month post second dose (n=172), 6 months post second dose (n=23) and 1 month post third dose (n=21). Demographic and clinical information including age, gender, DMT treatment and timing of COVID-19 vaccination were collected from 160 of these MS patients. Result(s): 151/172 sera at 1 month post second dose, 20/23 sera at 6 months post second dose, and 15/21 sera at 1 month post third dose were positive for Spike antibodies. Seropositive patients were treated on Alemtuzumab;n=3, Cladribine;n=32, Dimethyl fumarate;n=8, Fingolimod;n=16, IFN;n =4, Ocrelizumab;n=14, Ofatumumab;n=4, Natalizumab;n=11, Siponimod;n=1 and Teriflunomide;n=1. Out of the 21 patients who did not seroconvert at a month post second dose, treatment information was available in 12 patients. n=9 were treated by Ocrelizumab and n=2 were treated by Cladribine and n=1 was treated by Fingolimod, confirming certain DMTs prevent seroconversion. Out of the 151 patients that did seroconvert, 120 had titers that were comparable to controls (healthy general population) and 31 had reduced titres. Treatment information was available in 21/31 of these patients. Interestingly, 9/21 were on Ocrelizumab, 8/21 were on Fingolimod, 2/21 were on Ofatumumab, 1/21 was on Natalizumab and 1/21 was on Siponimod. This finding confirmed that certain DMTs such as Fingolimod, Ocrelizumab, Ofatumumab and Siponimod cause a reduction in post-vaccination Spike antibody titers in MS patients in comparison to general population. Expectedly, 304/304 sera were negative at baseline. Conclusion(s): Some High efficacy DMTs reduce Spike Ab titers or even prevent seroconversion. To maximize vaccine-mediated immune protection against COVID-19, timing of DMT administration and vaccine schedule may need intricate co-ordination in people living with MS.
ABSTRACT
Background: Current SARS-CoV-2 vaccines rely on protective immunity against early clade SARS-CoV-2 and have resulted in seroconversion in a subset of MS patients receiving immunosuppressive DMTs. However, it is unknown if SARS-CoV-2 spike antibodies afford immunity against emerging variants of concern, such as Delta and Omicron. Objective(s): To determine the binding of spike antibodies to early clade, Delta, and Omicron SARS-CoV-2 in patients with MS receiving different DMTs. Method(s): Spike antibody binding to early clade SARS-CoV-2, Delta and Omicron was assessed by flow cytometry using sera collected from 58 patients one month post second dose and one patient 1 month post third dose. All patients were previously determined to be seropositive against Wuhan (early clade spike). Clinical and demographic information including DMT treatment and vaccination timing was collected. Result(s): 53 patients were seropositive for Wuhan, Delta and Omicron spike antibodies. Wuhan Spike antibody titres were high at one month post second vaccination, whereas Delta and Omicron Spike antibody titres were significantly decreased. We observed a 70% and 93% decrease of in immunoreactivity to Delta and Omicron, respectively. Although ocrelizumab and fingolimod decrease Spike antibody titres after vaccination, they did not affect immunoreactivity to variants, in comparison to other DMTS. Conclusion(s): All 53 patients were able to generate a positive antibody response following vaccination. However, there was an observable decrease in the antibody titres and immunoreactivity to the Delta and Omicron variants, in comparison to Wuhan.
ABSTRACT
Background: COVID-19 vaccination induces protective Spike antibodies. Some responses are attenuated in people with multiple sclerosis (MS) on high efficacy disease-modifying therapies (DMT).Whether antibodies afford immunity against emerging SARS-CoV-2 Variants of Concern (VoC) such as Delta and Omicron is unknown. Aim(s): To assess the longevity and breadth of Spike antibody in MS patients after COVID-19 vaccination. Objective(s): To determine seroconversion and antibody binding toVoC Spike. Method(s): Spike antibodies to Clade A SARS-CoV-2 were assessed in 535 MS sera at baseline (n=292), 1 (n=141) and 6 month (n=67) post-second dose, and 1 month post-third dose (n=35), and 489 health worker controls. When known, COVID- 19 vaccines were BNT162b2 (n= 489 controls, n=108 MS patients) and ChAdOx1-S (n=37).Spike antibody binding to VoC Delta and Omicron BA1 was assessed in 68 sera 1 month post-second dose. Demographic and DMT information was available in 269 patients. Result(s): 123/141 sera at 1 month post-second dose, 66/67 at 6 months post-second dose, and 26/35 at 1 month post-third dose were positive for Spike antibodies.Patients who did not seroconvert at 1 and 6 month post-second and 1 month post-third dose (n=28) were treated with ocrelizumab (n=22), cladribine (n=1), fingolimod (n=4), and siponimod (n=1). At 1 month post-second dose, the median and IQR Spike antibody levels were 67,224+/- 101,251 in the seroconverted MS group compared to 145,510+/- 99,669 in controls (n=489). When patient sera were assessed for binding to Clade A Spike, and VoC Delta and Omicron BA1 Spikes, most sera were able to bind the three different Spike antigens (n=61). However, Spike antibody immunoreactivity was decreased by 70% against Delta Spike and 90% for Omicron BA1 Spike compared to the original clade A Spike.As observed for Clade A Spike antibody, DMTs, such as ocrelizumab, fingolimod, and ofatumumab, decreased the antibody binding to Delta and Omicron Spike. Still, the pattern of antibody recognition was similar between the three Spikes and all DMTs analysed, i.e. alemtuzumab, natalizumab, teriflunomide, and interferons. Our data suggest that, irrespectively of DMTs, antibodies generated after vaccination did not bind Spike from recent VoCs to the same extent as the original Spike used in COVID-19 vaccines. Conclusion(s): Some DMTs reduce Spike antibody titres or prevent seroconversion. The sequence of Spike used in the first generation of vaccines may need to be updated for emerging VoC.
ABSTRACT
Introduction: Cognitive difficulties experienced in MS impact areas such as work, socialising, self-care and many activities of daily living. There is a high prevalence of cognitive difficulties in MS, but despite this there are few programmes targeting cognition that focus on the ability to function well in everyday life. The COB-MS programme, an occupation-focused cognitive intervention, was developed to address this. It focuses on both the functional difficulties and the wide-ranging symptoms that present in MS, including the ability to maintain employment, social activities, home management and self-care. Objective(s): Here we report on the results of feasibility and initial efficacy of the COB-MS as a cognitive intervention for people with MS. Method(s): Although initially designed for in-person delivery, the COB-MS was adapted for online delivery due to the COVID-19 pandemic. Data was collected from people with MS experiencing cognitive difficulties at baseline, post-intervention, 12-weeks, and 6-month follow-up. The primary outcome measure was the Goal Attainment Scaling at 12 weeks. Data was also collected in cognition, quality of life, and mood. Result(s): One hundred and twenty-five people with MS and cognitive difficulties were randomised to either usual care or COB-MS intervention. Ninety-four participants were retained at 6-month follow-up. Fidelity data was collected and analysed for occupational therapist conducting the intervention. A qualitative evaluation of the COB-MS from the perspective of participants also took place. All feasibility results will be presented- preliminary efficacy, participant experiences, intervention fidelity, and overall outcomes from the trial. Conclusion(s):The results provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy.
ABSTRACT
Purpose : Age-related macular degeneration (AMD) is projected to affect an average of 1.23 million individuals by the 2050. Whilst anti-VEGF treatment for neovascular AMD (nvAMD) is considered the current gold-standard care, this requires regular monitoring and treatment delivery which causes increased capacity challenges. This, along with the current COVID-19 pandemic, have highlighted the need for efficient and safe ways to diagnose and manage nvAMD. The use of artificial intelligence (AI) in medical care has the potential to alleviate some of this projected pressure facing eye clinics. Previous research has shown that AI has comparable sensitivity and specificity to clinicians in identifying ocular disorders from retinal images. The purpose of the current study was to develop and AI model to identify active from inactive nvAMD disease from retinal SD-OCT images. Methods : Using Google's Vision AutoML software, 1058 Heidelberg SD-OCT images were identified and labelled as either showing nvAMD activity or inactivity. All images were uploaded to Google's cloud storage and automatically assigned two bounding-box labels;1 label capturing the entire Heidelberg SD-OCT image, including the raster and b-scan, with the second capturing the b-scan only. All labels were automatically allocated to either a train, validate or test group based on an 80:10:10 ratio set by the software. Results : Of the 1058 images, a total of 2116 labels were assigned, 1012 showing active and 1104 showing inactive nvAMD. Performance of the AI model revealed an area under the precision recall curve (AUPRC) of 0.84 at a threshold of 0.5, specificity of 40.98% and sensitivity of 95.24%. For the active-only images, the specificity was 34.28% with a sensitivity of 97%. For the inactive-only images, the specificity was 51% with a sensitivity of 92.73%. Conclusions : Utilising Google's AutoML AI software, this model is able to correctly identify active nvAMD from Heidelberg SD-OCT images with a high level of sensitivity and good overall AUPRC.
ABSTRACT
Approximately 43-70% of people living with multiple sclerosis (MS) experience cognitive impairment. This study-within-a-trial (SWAT) takes place within a host trial investigating the feasibility of the Cognitive-Occupation-Based programme for people with MS (COB-MS), a holistic therapy on the management of cognitive symptoms in MS. Reliable remote cognitive testing could provide safer and more convenient care for MS patients, during the COVID-19 pandemic and thereafter. The SWAT examines the reliability of delivering the Brief International Cognitive Assessment for MS (BICAMS) and the Trail-Making Test (TMT) remotely to people to 68 people with MS experiencing cognitive difficulties. Group 1 (N=34) were tested in-person pre-pandemic. Group 2 were tested remotely. No significant differences between virtual and in-person administrations of the CVLT-II and SDMT were detected. BVMT-R scores were significantly higher for virtual administrations, possibly indicating inter-rater differences. Strong positive correlations were found for in-person and virtual scores within Group 1 on the CVLT-II. The findings support the reliability of remote administration of BICAMS and the TMT in people living with MS. Future research with larger samples could investigate performance on BVMT-R with regards to screen size of device used.
ABSTRACT
An online survey (N=709) explores correlates of use of new online meetings and changes in use of social media during early stages of the COVID-19 pandemic in the U.S.A. The motivation for this study is that the pandemic presented an opportunity to assess the degree of use of online communication technologies when faced with new risks and other options are severely limited. The survey context was set by first probing worries about the virus and the degree of social distancing being practiced. Coping mechanisms reported included connecting more with friends and family on social media, including about 2/3 who had joined an activity that moved online during social distancing. Extent of social distancing and age were significantly related to degree of online engagement in a new meeting activity during the early stages of the pandemic. Age and gender were significantly related to changes in level of use of social media. © AMCIS 2021.
ABSTRACT
Introduction: The COVID-19 pandemic has had a significant impact on research and health care in MS. This study-within-atrial (SWAT) takes place within a host trial investigating the feasibility of the Cognitive-Occupation-Based programme for people with MS (COB-MS) that was originally designed to be delivered in-person but was amended to an online environment. As such, reliable remote cognitive testing could provide safer and more convenient care for MS patients. Aims: The SWAT examines the reliability of delivering the Brief International Cognitive Assessment for MS (BICAMS) and the Trail-Making Test (TMT) remotely to people with MS. Objectives: Performance on BICAMS measures and the TMT administered remotely are compared with performance on tests administered in-person. BICAMS measures include the California Verbal Learning Test, Second Edition (CVLT-II), the Symbol Digit Modality Test (SDMT) and the Brief Visuospatial Memory Test-Revised (BVMT-R). Method: Independent samples t-tests were conducted on a sample of 68 participants to investigate differences in performance between Group 1 (11 males, 23 females), who were visited by a research assistant in their homes before the pandemic and Group 2 (10 males, 24 females) who received online testing only via teleconference platform Zoom. Within-group differences for Group 1 who also received virtual testing after a six-month interval were also examined. Results: The analysis revealed no significant differences in scores between virtual and in-person administrations of the CVLT-II, TMT and SDMT. Strong positive correlations were found for inperson and virtual tests within Group 1 after a six-month interval on the CVLT-II, SDMT, TMT-A and TMT-B. BVMT-R scores were significantly higher for virtual testing (M = 20.59, SD = 6.65) compared to in-person testing (M = 16.35, SD = 6.05). However, this discrepancy may be attributed to inter-rater differences, rather than enhanced performance for online testing. In-person and virtual assessments within Group 1 were also strongly correlated (r = .72). Conclusions: The findings support the reliability of remote administration of BICAMS and the TMT in people living with MS.