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Introduction: The impact of the COVID-19 pandemic on people living with multiple sclerosis (MS) is expected to be significant. Whilst quantitative research in this area has been undertaken, there is a paucity of qualitative research;this study will therefore provide valuable insights into individual experiences and perceptions of people with MS (PwMS) in the United Kingdom (UK) during this unique period. Objective(s): The ongoing global health crisis leaves us all in a state of uncertainty that requires constant adaptation to the new 'normal' we are living in, and it is important that the challenges faced by the MS community are recognised and addressed as part of this learning process. We explore self-reported data gathered during the pandemic to reach conclusions regarding the impact of the crisis on PwMS. Aim(s): To enhance understanding of the experiences of PwMs during the COVID-19 pandemic and identifying potential areas where further support could be beneficial. Method(s): Between March 3 and October 29, 2020, 1,685 free-text comments regarding the unique experiences of PwMS were collected online by the UK MS Register (UKMSR). Thematic analysis of 1,000 randomly selected responses made by 682 individuals was used to investigate the perceived impact of COVID-19 on the participants, following a constructivist approach. Result(s): Five main themes were identified in the data: connectedness, attitudes towards change, mental health, stigma, and information and advice. Results of the thematic analysis were varied, with significant numbers reporting positive experiences of the pandemic. Conclusion(s): Individual levels of connectedness and attitude towards change significantly influence how PwMS experience life during the COVID-19 outbreak. The data showed the impact of COVID-19 on mental health to be mixed among PwMS. The pandemic hashighlighted that some PwMS remain fearful of being stigmatised in the workplace because of their condition.
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Introduction: Online registries enable home-based, cost-effective and long-term follow up. The benefits were highlighted during the pandemic where lockdowns limited engagement with health professionals. The UK MS Register has been collecting patient reported outcomes (PROs) over 11 years. PROs consist of a number of questions summed to form a total, however, each question has a scale and addresses a particular problem. Objectives/Aims: We investigated the responses to individual questions of the Multiple Sclerosis Impact Scale (MSIS-29) and the Hospital Anxiety and Depression Scale (HADS) through a series of lockdowns throughout the evolving crisis. Method(s): We studied 5 timepoints (March 2019, September 2019, March 2020, September 2020, March 2021) spanning the pandemic. ~1000 patients completed all timepoints. We studied how the responses to each questionnaire item changed, evaluating the %patients who reported an increased, decreased or stable rating of each item over each 6-months window (e.g. March-September 2019). We then quantified the change in %patients across windows. Significance was evaluated using permutation testing. Result(s): >50% patients stayed stable across all questionnaire items over a period of 6 months and the remaining patients either got better or worse. This fluctuating behaviour is not unexpected in MS. The change in %patients reporting an increased, decreased and stable item rating over 6-months periods did not change significantly for most items. Notably, the items where a significant change was observed, could be directly related to Covid-19 given the nature of the question. These included "feeling stuck at home", "having to cut down time spent on work" and "feeling limited in your social and leisure activities" for MSIS-29 and "feeling frightened something awful is about to happen", "being able to see the funny side of things" and "losing interest in your personal appearance" for HADS. Conclusion(s): PROs capture disease specific elements, including MS patients variability and fluctuating symptoms, but are also sensitive to external factors such as the social context. When considering the questionnaires' total scores this information can be lost. Detailed item-level analyses can help disentangle the causes behind observed trends and the relations between disease-related and external factors (e.g. covid in this specific case) adding to the relevance of PROs in monitoring disease long-term.
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Background: COVID-19 vaccine hesitancy has been asscociated with social deprivation and selected minority ethnic groups who are over-represented in the Renal Replacement Therapy (RRT) population. We designed a COVID-19 vaccination programme for our RRT population with the aim to increase vaccination uptake and decrease health inequalities. Method(s): Key interventions included addressing vaccine hesitancy by deploying the respective clinical teams as trusted messengers, prompt eligible patient identification and notification, deployment of resources to optimise vaccine administration in a manner convenient to patients and timely collection and analysis of local safety and efficacy data. First COVID-19 vaccination uptake data in relation to ethnicity and social deprivation, measured by the multiple deprivation index, in our RRT population were analysed and compared with uptake data in the regional total adult clinically extremely vulnerable (CEV) population in Greater Manchester (GM). Univariate logistic regression analysis was used to explore the factors associated with not receiving a vaccine. Result(s): Out of 1156 RRT patients included in this analysis (Table) 96.7% received the first dose vaccination compared to 93% in the cohort of CEV patients in the GM. Age, sex, ethnicity and index of multiple deprivation were not associated with first dose vaccine uptake. Vaccine uptake in Asian and Black RRT patients was 94.9% and 92.3% respectively compared to 93% and 76.2% for the same ethic groups in the reference CEV GM. Vaccine uptake was 96.1% of RRT patients in lowest quartile of multiple deprivation index compared to 90.5% in the GM reference population. Conclusion(s): Bespoke COVID-19 vaccination programme based on local clinical teams as trusted messengers can address vaccine hesitancy and reduce health inequalities.
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INTRODUCTION: Methoxyflurane is an historical anaesthetic agent that has undergone a renaissance with the introduction of a smaller dose in a handheld 'Penthrox' device. The benefits of Penthrox include its ease of use, with disposable individual packets, and the need for less monitoring and staff, when compared with deeper sedation. The literature acknowledges its use for analgesia and in the management of anterior shoulder dislocation but in no other procedural orthopaedic circumstance. METHODS: Following institutional approval, we undertook a retrospective review of all incidences of Penthrox use to facilitate minor procedures within a 2-month period starting 24 March 2020. Time to procedure and success were recorded using the surrogate markers of patient attendance and x-Ray occurrence times. RESULTS: Some 101 Penthrox doses were given to 89 patients over 97 unique episodes between 24 March and 26 May 2020. No complications were recorded following the use of Penthrox during this period. Patient demographics were explored. Fracture manipulations and casting (n=54) had a 100% success rate in achieving adequate and safe reduction. Joint dislocations (n=34) were treated with varying success. Native elbow dislocations were reduced most successfully (4/4, 100%). Native shoulder dislocations were seen in 17 patients and successful relocation was seen in 11 cases, giving a success rate of 65%. CONCLUSIONS: This is the first study, outside anterior shoulder dislocations, to report on the efficacy of Penthrox within emergent orthopaedic scenarios. We have demonstrated Penthrox to be a safe tool for helping to manage trauma procedures in the emergency department.
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Introduction The UK MS Register (UKMSR) has collected longitudinal patient reported outcomes (PROs) on pwMS regularly since 2011. Aim to assess changes in disability and quality in life (QOL) in the UKMSR before and during the pandemic Methods pwMS who answered the PROs: web EDSS to assess disability in MS and EQ5D-3L visual analogue scale for QOL, six months prior to the pandemic (t-6), at the start (t0), and six months after (t+6). Results 1553 pwMS completed QOL assessment. Of the 458 who started with a lower QOL (<50) there was improvement at t0 which stabilised at t6 (t-6=34, t0=40, t6+=39, x2=89.91, p<0.001). In those starting with a QOL 350 their QOL worsened at the start of the pandemic (t-6=75, t0/t +6=71, x2=58.28, p<0.001). web EDSS scores were completed by 902 pwMS. There was no change in 501 pwMS with an initial web EDSS 36.0. In 401 pwMS with a web EDSS score <6 there was a worsening in median score at t0 but not then at t6 (t-6=3.0, t0/t +6=3.5, x2=21.57, p<0.001), QOL also worsened in a similar pattern in this group. Conclusion Disability and QOL worsened in those doing better at the start of the pandemic. Whereas in those more significantly affected, disability remained stable and QOL improved.
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Background The UK MS Register (UKMSR) has been capturing longitudinal clinical and patient reported outcomes (PROs) since 2011. As the UK population 'locked-down' in March 2020 it became important that clinicians could record hospitalised MS patients due to COVID-19 and record outcome. The UKMSR provided an electronic case return form, designed collaboratively by the community. Aim Impacts of disability, age and treatment on mortality in pwMS with COVID-19 Method Linear modelling and standardised hypothesis testing were performed on an outcome of died or not, impact of disability (EDSS), disease modifying therapies and age. Results N=132 PCR confirmed COVID-19 patients submitted, 14 missing EDSS, leaving n=118. Female n=80, n relapsing =74, n progressive = 44, mean age 49.2. Median EDSS = 5.0. Linear regression for age was found to be most significant for outcome (p=0.002). Univariate analysis found that the outcome was not independent of EDSS (ChiSq p=0.0008), DMT (ChiSq p=0.006) and MSType (ChiSq p=0.0006). In the multivariate model only, age remained significant. Conclusions Only age remained as a marker of poor outcome multivariate analysis. No MS Specific characteristics were found to be significant. We would encourage continued data collection from UK neurology centres to increase the utility of this data.
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Introduction Global efforts in vaccine development against SARS-CoV-2 saw the Pfizer-BioNTech vaccine approved for use in the United Kingdom (UK) on 2nd December 2020. There have long been discussions around vaccination in patients with multiple sclerosis (pwMS). We conducted a patient survey as part of the UK MS Register (UKMSR), to understand pwMS views on COVID vaccination. Method PwMS were invited by email to complete a COVID-19 vaccine online questionnaire as part of the UKMSR on 7th December 2020. Results A total of 3092 pwMS completed the survey by 7th January 2021. 69.1% of patients indicated they are definitely going to get a COVID-19 vaccine, 16.1% probably, 9.1% possibly, 3.4% probably not and 2.3% definitely not. Factors examined includes gender, age, highest educational attainment and type of MS. Additionally, we explored whether previous experiences of vaccinations affected attitudes towards COVID vaccination. The top reasons for not taking a COVID vaccine included safety concerns and insufficient information. Conclusion This UKMSR patient survey showed 85.2% of pwMS intend to get vaccinated against SARS-CoV-2, which is higher than the UK general public of 67% (1). More information on vaccine safety in pwMS would be helpful in making informed decisions.
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COVID-19 is a concern in people with multiple sclerosis (MS), mostly because of their long-term physical disabilities and immunomodulatory disease-modifying therapies (DMTs). In this community-based pro-spective longitudinal study, we have been monitoring a cohort of people with MS via the web-based platform of the UK MS Register since the start of the COVID-19 outbreak. We report our findings from 17/03/2020 to 15/01/ 2021. Out of 7344 participants, 883 (12%) have reported a selfdiagnosis of COVID-19 of whom 211 had a confirmed clinical or laboratory-based (n=114) diagnosis. No individual DMT increased the likelihood of contracting COVID-19 (with any of the diagnoses as the outcome). Gender (male: female, adjusted OR: 95% CI [0.94: 0.68'1.3]), web-based Expanded Disability Status Scale score (webEDSS;one-point increase, 0.92: 0.84'1.01), and MS duration (one-year increase, 1: 0.98'1.02) were not associated with contracting COVID-19. Younger age (one-year decrease, 1.04: 1.03'1.06), ethnicities other than white (1.95: 1.13'3.34), and relapsing-remitting MS (versus progressive, 1.72: 2.56'1.16) increased the likelihood of contracting COVID-19. Within a median (interquartile range) of 26 (0'72) days follow-up of participants with COVID-19 (n=532), 69% reported full recovery. A higher webEDSS (one-point increase, 0.84: 0.74'0.96) lowered the likelihood of full recovery. Overall, MS-specific factors do not predispose people with MS to contracting COVID-19, but physical disability can delay recovery.
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This editorial is in support of an issue of the Journal that has a focus on educational technology (EdTech). With this in mind, this editorial will provide advice on how the editorial team for this section feels that educational technology will evolve into the latter part of the 2020’s, especially given the disruption caused by the COVID-19 pandemic. Examples are given of how writing in this space has changed over the years of the pandemic, with a history of EdTech given, followed by an argument for the need for technology to be used in context. This is followed by descriptions of good practice around theoretical framing, methodology rigour, inclusion of the people element, and the need for the technology to serve a purpose. The piece concludes with a summary of where the editorial teams feels the field will go from here into the future. Throughout, practical examples of submissions made over the last few years are given to help illustrate a coherent direction. It is anticipated that this editorial will serve as a guide for future authors to use in service of better educational technology outputs in the future. Practitioner Notes 1. The use of technology in education needs to serve a purpose. 2. Theoretical framing is an essential underpinning of any EdTech practice. 3. EdTech research needs to ensure it embodies valid and reliable research methods and measures for evaluation. 4. Technology needs to enhance learning in all contexts, regardless of mode of learning. 5. EdTech researchers need to ensure that people and their behaviours are reflected in the technology-based processes. © 2022, University of Wollongong. All rights reserved.
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Introduction: Systemic inflammatory conditions (e.g. sepsis and severe viral infections like COVID-19) are characterized by an overwhelming innate immune response that leads to multi-organ failure [1]. Decellularized extra cellular matrices (ECM) have previously demonstrated pro-regenerative properties through modulation of the immune response [2]. Infusible ECM (iECM) was developed for systemic delivery, targeting and treating sites of vascular injury. We hypothesized iECM delivery would dampen the systemic inflammatory response in a lipopolysaccharide (LPS) mouse model. Methods: iECM was prepared from decellularized porcine left ventricle based on previous protocols [3]. C57BL6/J mice underwent dual intraperitoneal LPS injection and then tail vein injection of saline or iECM (10 mg/mL). Thirty hours post-LPS dose, mice were euthanized and heart, lungs, brain, kidneys, spleen, and liver were harvested (n = 6 mice/group). Tissues were processed for gene expression by qRT-PCR and Nanostring nCounter® Immunology Panels, immune cell identification by flow cytometry, and cytokines by Legend Plex® Mouse Inflammation Panels. Results: qRT-PCR identified significant downregulation of Il1b and Il6 across multiple tissue types in iECM vs. saline-treated mice. Nanostring transcriptomic analysis confirmed downregulation of multiple inflammatory cytokines and chemokines. IL-6 cytokine expression was significantly reduced across multiple organs along with IL-1α and IFN-γ in the lungs, and IL-1β and IL-17A in the spleen. Discussion: Results demonstrated iECM dampens the systemic inflammatory response to LPS, indicating its potential for treating conditions such as sepsis and COVID-19 pathology.
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Aim: The aim of this study was to understand the challenges that nurses and midwives face when seeking to practice social distancing within the various clinical settings in a hospital work environment during COVID-19. Background: COVID-19 has had a significant impact on nurses and midwives internationally. With the ease of transmission of COVID-19 and the limitations in pharmaceutical interventions, other measures had to be implemented across communities and in healthcare settings. These public health measures were enacted in various ways throughout the world. A key measure employed globally was social distancing. Australia was no different, initiating community wide interventions to apply social distancing principles and action, in an effort to reduce transmission. Whilst at their places of work, nurses and midwives were also encouraged to practice social distancing. Design and methods: Using convenience sampling, 579 nurses and midwives employed within one local health district in NSW, Australia completed an online questionnaire during the COVID-19 pandemic. Subsequently, a thematic analysis was undertaken as a way of categorising data from the 216 (37%) qualitative responses with regards to social distancing. This study adhered to The Standards for Reporting Qualitative Research (SRQR) guidelines. Results: Overwhelmingly, responses indicated that participants found it challenging to practice social distancing in their workplaces across various clinical settings within the hospital. The two major themes identified were: 1) challenges relating to social distancing with patients and 2) challenges related to social distancing with colleagues. Several sub themes were also identified. Conclusion: The COVID-19 pandemic has highlighted a number of challenges for healthcare professionals, social distancing being a key challenge. Social distancing is argued to be almost impossible in various clinical settings within a hospital where patient contact and provision of care in a team environment occurs. © 2022 Australian Nursing and Midwifery Federation. All rights reserved.
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The COVID-19 study (clinicaltrials.gov:NCT04354519) is a prospective observational cohort launched on 17 March 2020 as part of the UKMSR. As of 24 April, out of 3910 participants, 237 (6.1% (95% CI 5.3% to 6.8%)) reported self-diagnosed COVID-19 among whom 54 (22.8% (17.5% to 28.2%)) also had a diagnosis by a healthcare professional based on symptoms and 37 (15.6% (11.2% to 20.6%)) a confirmed diagnosis by testing. Three participants reported hospitalisation due to COVID-19. No deaths were reported. Among 1283 siblings without MS, 79 (6.2%) had a reported diagnosis of COVID-19. Adjusting for age and gender, the likelihood of contracting COVID-19 in pwMS was similar to siblings (OR 1.180 (0.888 to 1.569)). Seven hundred and fifty-nine of 3812 participants reported that they were self-isolating and that they had been self-isolating for at least 2 weeks before symptom onset if they had COVID-19. Of these, 2 (0.3% (0% to 0.7%)) had self-diagnosed COVID-19 whereas 137 of 3053 participants not self-isolating (4.5% (3.8% to 5.2%)) had the disease. Participants on DMTs were less likely to have self-diagnosed COVID-19 (OR 0.640 (CI 0.428 to 0.957)), which remained significant after removing self-isolating participants (OR 0.633 (0.402 to 0.998)). High-efficacy DMTs reduced the likelihood of self-diagnosed COVID-19 compared with no DMTs (OR 0.540 (0.311 to 0.938)) but not compared with moderate-efficacy DMTs. Including webEDSS (n=2808) and physical MSIS-29v2 (n=3192) as additional predictors in the analysis showed no significant association with the likelihood of contracting COVID-19. The gender distribution was similar between participants with and without COVID-19. More participants with self-diagnosed COVID-19 reported themselves as having any ethnicity other than white compared with those without the disease (6.9% (3.9% to 10.1%) vs 3.8% (3.2% to 4.4%), p=0.019). Gender and ethnicity did not affect the likelihood of having COVID-19.
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Background: Rapidly worsening symptoms in multiple sclerosis (MS) can be associated with relapses or temporary changes due to systemic disturbances such as an increase in temperature eg Uthoff's phenomena. COVID-19 infections can exacerbate MS symptoms (Garjani, 2021), notably this worsening seems to be ameliorated by disease modifying therapies (DMT). Vaccinations have a long history of issues for people with MS (pwMS) as they have been associated with MS worsening. COVID-19 vaccines were developed rapidly and have been associated with vaccine related side effects that we are continuing to establish Objective: To determine the range of side effects from the AstraZeneca (AZ) and Pfizer (PF) vaccines in pwMS and factors associated with their occurrence Methods: A vaccine survey was deployed to all pwMS on the UK MS Register, which remains accessible to all participants. First dose vaccine type and effects were collected and linked with demographics and prior COVID-19 studies. Control data was derived from a UK-wide observational study focusing on particular matched questions (Menni et al, 2021). Results: As of 23-Mar-21, 388/1154 (34.5%) had vaccine effects with the PF vaccine and significantly more 822 /1408 (58.4%) had vaccine effects from the AZ vaccine (p<0.0001). There was no difference in the rate of severe side effects between the two vaccines (2.4% AZ,1.03% PF). Particular symptoms: fatigue, headaches and fever could be matched with control data. Fatigue: AZ-MS 59.3% v 21.1% controls;PF-MS 47.4% vs 8.4% controls Headaches: AZ-MS 58.3% v 22.8% controls;PF-MS 43.0% vs 7.8% controls Fever: AZ-MS 26.5% v 8.2% controls;PF-MS 11.1% vs 1.5% controls Sensory loss: AZ-MS 7.5%;PF-MS 3.4%. No control comparison. Logistic regression for the presence of vaccine effects (vs none) was associated with younger age (0.97 [0.96, 0.98], (<0.0001): odds ratio [95%CI], p), female gender (0.56 [0.45, 0.70], (<0.0001), prior COVID-19 infection (1.98 [1.24, 3.21], 0.0049) and the AZ vaccine (2.93 [2.45, 3.51], < 0.0001). Notably being on a DMT, higher disability and progressive MS were not significant. No factors were associated with severe reactions. Conclusion: In MS, as in other studies vaccine effects are more prominent in the AZ group compared to PF but there is no difference in severe vaccine effects. Systemic symptoms fever, headaches and fatigue are more common in MS than in a control population with associated increases in sensory symptoms.
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Introduction: Neurological symptoms of COVID-19 such as fatigue and cognitive and mental health problems constitute the most common long-lasting symptoms of the infection (long COVID) and are also prevalent in MS. Objectives: To assess the prevalence of and factors associated with long COVID in people with MS (pwMS). Aims: To understand how pwMS are affected by long COVID. Methods: This is an ongoing prospective and longitudinal community- based observational study in a national cohort of pwMS who have been reporting whether they have had symptoms suggestive of COVID-19 using the online questionnaire-based platform of the UK MS Register (UKMSR) since 17/03/2020. PwMS with COVID-19 have been regularly followed up to update their recovery status. Here, we report the findings until 19/03/2021. The UKMSR holds demographic and clinical data of registered pwMS and their pre-COVID-19 web-based Expanded Disability Status Scale (web-EDSS) and Hospital Anxiety and Depression Scale (HADS) scores (HADS scores ≥11 were considered as probable anxiety or depression), which allowed us to examine the effects of these variables on recovery from COVID-19 using multivariable Cox regression analysis. The results will be updated prior to ECTRIMS 2021. Results: Out of 1,096 pwMS with COVID-19, 599 updated their recovery status (participants);their median (interquartile range) age was 50 (41-57) years and 462 (77.1%) were women. 458 participants (76.5%) reported full recovery and 141 participants (23.5%) had persistent symptoms at their last follow-up. At least 181 participants (31.1%) had persistent symptoms for ≥4 weeks and 76 (13.1 %) for ≥12 weeks. Participants with higher web- EDSS scores (adjusted Hazard Ratio: 95% Confidence Interval, 0.92: 0.86-0.98), participants with anxiety and/or depression (0.70: 0.53-0.92), and women (0.78: 0.63-0.97) were less likely to recover from COVID-19. Taking DMTs was not associated with recovery from COVID-19 (0.92: 0.74-1.14). Conclusion: The prevalence of long COVID in pwMS appears to be higher than the general population (13.3% ≥4 weeks and 2.3% ≥12 weeks), and those with higher levels of pre-COVID-19 neurological impairment or mental health problems are at higher risk of long COVID. We have previously shown that COVID-19 can also lead to MS exacerbations. These observations indicates that pwMS require individualised pathways for the effective management of their post-COVID-19 rehabilitation.
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BACKGROUND: In March 2020, the United Kingdom Multiple Sclerosis Register (UKMSR) established an electronic case return form, designed collaboratively by MS neurologists, to record data about COVID-19 infections in people with MS (pwMS). OBJECTIVES: Examine how hospital admission and mortality are affected by disability, age and disease modifying treatments (DMTs) in people with Multiple Sclerosis with COVID-19. METHODS: Anonymised data were submitted by clinical teams. Regression models were tested for predictors of hospitalisation and mortality outcomes. Separate analyzes compared the first and second 'waves' of the pandemic. RESULTS: Univariable analysis found hospitalisation and mortality were associated with increasing age, male gender, comorbidities, severe disability, and progressive MS; severe disability showed the highest magnitude of association. Being on a DMT was associated with a small, lower risk. Multivariable analysis found only age and male gender were significant. Post hoc analysis demonstrated that factors were significant for hospitalisation but not mortality. In the second wave, hospitalisation and mortality were lower. Separate models of the first and second wave using age and gender found they had a more important role in the second wave. CONCLUSIONS: Features associated with poor outcome in COVID-19 are similar to other populations and being on a DMT was not found to be associated with adverse outcomes, consistent with smaller studies. Once in hospital, no factors were predictive of mortality. Reassuringly, mortality appears lower in the second wave.
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COVID-19 , Multiple Sclerosis , Humans , Male , Multiple Sclerosis/epidemiology , Multiple Sclerosis/therapy , Pandemics , Patient Reported Outcome Measures , SARS-CoV-2ABSTRACT
Objective: To assess factors associated with recovery from the coronavirus disease 2019 (COVID-19) among people with multiple sclerosis (pwMS) Background: It is important to understand the recovery process from COVID-19 among pwMS to identify those who are most vulnerable to the long-term sequelae of infection. Design/Methods: The UK MS Register COVID-19 study is a community-based prospective cohort of pwMS launched on March 17th, 2020. We have been collecting data from participants (n=6,618 as of October 5th, 2020) every two weeks from the time of their enrolment in the study. We ask participants about COVID-19 and follow them through their recovery. The UK MS Register holds pre-COVID-19 longitudinal and prospectively collected patient-reported data including web-based Expanded Disability Status Scale (webEDSS), MS Impact Scale (MSIS-29), and Hospital Anxiety and Depression Scale (HADS) scores. Results: Out of 709 participants with self-diagnosed COVID-19, 391 responded to the follow-up questionnaires. 76% (n=297) had fully recovered, 15.9% (n=62) had mostly recovered, and 8.2% (n=32) were still experiencing symptoms at the time of their latest follow-up. Among participants with full recovery, the median (IQR) duration of disease was 10 (6-21) days. Participants who had not recovered completely had been followed up for a median (IQR) duration of 105 (35-131) days. PwMS who had a higher webEDSS score (OR 0.78, 95%CI 0.65-0.93) or physical component of MSIS-29 score (OR 0.97, 95%CI 0.96-0.98) were less likely to report a full recovery. The presence of anxiety (HADS-anxiety ≥11), recorded the year before the pandemic, was associated with a lower probability of complete recovery (OR 0.26, 95%CI 0.10-0.66). Demographics, diseasemodifying therapies, MS duration, or type of MS were not associated with recovery. Conclusions: Physical disability and anxiety prior to the pandemic are the main determinants of persistent COVID-19 symptoms among people with MS.
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Rationale: Multi-organ failure (MOF), associated with conditions such as acute respiratory distress syndrome, sepsis, and the recent SARS-CoV-2 virus, often exacerbates disease severity by the overwhelming systemic inflammation, thus, highlighting the need for alternative therapeutics. To address this need, intravascularly delivered infusible extracellular matrix (iECM) material was evaluated in a sepsis mouse model using lipopolysaccharide (LPS). Immunomodulatory properties of decellularized ECM that have demonstrated endogenous tissue repair promotion could favorably mitigate systemic inflammation pathology related to MOF. Compared to decellularized ECM or injectable ECM hydrogels where deployment is limited to a specific tissue per procedure, intravascular iECM delivery targets leaky vasculature in areas of inflammation. We hypothesized iECM could simultaneously alleviate systemic inflammation across multiple vulnerable tissues, thus, demonstrating potential to mitigate MOF in systemic inflammatory conditions. Methods: iECM was generated as previously described1. Porcine left ventricular tissue was decellularized, lyophilized, milled into fine powder, and 2-day pepsin digested. Insoluble ECM proteins were pelleted by high-speed centrifugation, supernatant was dialyzed in 100- 500 Da tubing, and dialyzed ECM was lyophilized, resuspended with 1x PBS, and sterile filtered. Resulting iECM was aliquoted and lyophilized for storage until resuspended with deionized water. A dual LPS-LPS mouse was utilized for modeling severe systemic inflammation. Nine-week female C57BL6/J mice underwent the following procedures: 1) Intraperitoneal (IP) injection of LPS (10 mg/kg), 2) IP LPS injection (1 mg/kg) at 6 hours for further prolonged and severe inflammation, 3) 200 μL tail vein injection of saline or iECM (10 mg/mL) at 10 hours (n = 6 per group), and 4) euthanasia and harvesting of lungs, heart, brain, and kidneys for gene expression analysis by qRT-PCR and Nanostring nCounter® Immunology Panel (Mouse). Results: Il1b and Il6 trended (p < 0.1) lower for the lungs while both were significantly decreased for the heart following iECM delivery. Additionally, Il6 was significantly decreased in the brain and kidney (Fig 1A). Multiplex profiling of lungs demonstrated inflammatory marker downregulation, including Il6, Il1α, and various chemokines (Fig 1B). Gene enrichment determined modulation of inflammatory cytokine profiles along with immune cell activation, proliferation, migration, and differentiation. Similar results were determined for the heart, brain, and kidney (data not shown). Conclusion: Systemic immunomodulation was observed among multiple affected organs, demonstrating iECM's potential for mitigating systemic inflammatory responses. Future work will investigate infiltrating immune cell subpopulations, validate results through proteomic analysis, and complete long term tissue morphology and functional assessments.
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Background: The UK MS Register captures longitudinal data directly from people with MS (pwMS) as patient reported outcome measures but also from NHS Trusts via electronic Case Return Form (eCRF). As part of our response to the COVID19 pandemic we designed an anonymised clinical capture instrument to allow clinicians from non affiliated NHS hospitals capture important clinical data on incident cases. Here we outline our current clinicians reported findings from these collected data. Objectives: Report on patients with Multiple Sclerosis and COVID as reported by UK National Health Service MS clinicians to the UK MS Register Methods: Data were captured using the RedCap platform to design forms and were stored on secured databases at Swansea University Medical School. The URL for data capture was shared on social media and via clinician groups to encourage as many clinicians as possible to report hospitalised pwMS and confirmed COVID. Variables included: Age, Gender, MS Type, Expanded Disability Status Score (EDSS), Disease Modifying Therapy (DMT) Details, COVID clinical treatment and outcomes. Results: Between 27/03/2020 and 14/07/2020, 93 patients with COVID were reported. Their mean Age was 53.38 (±14.2) and median EDSS 6.0. Of these 11 patients died with mean Age 63.7(±10.9). Median EDSS 8.0. Multivariate regression showed increased EDSS score to be the most significant factor for mortality (P <0.01) with the other variables (age, gender, disease type, DMT,) not influencing mortality. All the patients that died had progressive MS and only one was on a DMT. Conclusions: Here we present the UK PwMS, with laboratory confirmed COVID19 as reported by hospital clinicians. We found increased disability rather than age or MS type to be the only predictor of mortality. These results are strikingly different from the patients reported UK MS register COVID study (separate abstract) that had a much milder COVID illness that led to hospitalisation in only 3% of the cases.