AI-enabled multiscale modeling of SARS-CoV-2 replication transcription complex

The severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.g., cryo-electron microscopy and all-atom molecular dynamics (AAMD), do not provide sufficiently high resolution or timescale to capture important dynamics of this molecular machine. Consequently, we develop an innovative workflow that bridges the gap between these resolutions, using mesoscale fluctuating finite element analysis (FFEA) continuum simulations and a hierarchy of AI-methods that continually learn and infer features for maintaining consistency between AAMD and FFEA simulations. We leverage a multi-site distributed workflow manager to orchestrate AI, FFEA, and AAMD jobs, providing optimal resource utilization across HPC centers. Our study provides unprecedented access to study the SARS-CoV-2 RTC machinery, while providing general capability for AI-enabled multi-resolution simulations at scale. We acknowledge funding from NIH P41-GM10460, DOE CSGF (DE-FG02-97ER25308), Exascale Computing Project (17-SC-20-SC) and National Virtual Biotechnology Laboratory.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

The Rowan Hillson Inpatient Safety Award 2022 The best interventions: redesigning, rebuilding and maintaining safe inpatient diabetes care during COVID

Introduction: The annual National Diabetes Inpatient Audit (NaDIA and NaDIA-Harms) in the UK continues to show significant problems with patient care. During the COVID pandemic patient care has been even more difficult. New initiatives are urgently required to improve inpatient safety for people with diabetes. Method: The Joint British Diabetes Societies for Inpatient Care (JBDS-IP) organised the seventh national Rowan Hillson In-patient Safety Award on the theme of "the best interventions: redesigning, rebuilding and maintaining safe inpatient diabetes care during COVID". Result: The winner was the DEKODE team, led by Dr Punith Kempegowda from University Hospitals Birmingham NHS Foundation Trust, for their innovative quality improvement project across hospitals during COVID to improve diabetes-related ketoacidosis (DKA) management and study DKA in people with COVID. Adherence to national guidance improved in some hospitals, with falls in hypoglycaemia, and overall there was a significant improvement in awareness about DKA amongst junior doctors. The King's College NHS Foundation Trust team, led by Adrian Li and colleagues, received the highly commended award for their innovative project of remote blood glucose (BG) monitoring across healthcare boundaries. This improved diabetes control and tackled health inequalities. Summary and conclusion: These and similar schemes need to be developed, promoted and shared to improve safety for people with diabetes admitted in hospital during COVID times.

Humoral immune responses to SARS-CoV-2 vaccines in an ozanimod open-label extension study

Background: Ozanimod, an oral sphingosine 1-phosphate receptor modulator, is approved in the European Union and United States for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing multiple sclerosis (RMS). A previous analysis of data from UC and multiple sclerosis (MS) open-label extension (OLE) studies showed that most patients with confirmed coronavirus infection (COVID-19) had nonserious infections, recovered, and did not require ozanimod discontinuation. Some immunomodulators and biologics may attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response;therefore, this analysis evaluated humoral immune responses and predictors of response to SARS-CoV-2 vaccination in patients with RMS treated with ozanimod. Method(s): RMS participants who completed a phase 1-3 ozanimod trial could enter an OLE trial (DAYBREAK;NCT02576717) of ozanimod 0.92 mg/d. This analysis (January 2020-October 2021) included DAYBREAK participants receiving mRNA or non-mRNA SARS-CoV-2 vaccines (1-2 doses, vaccine-dependent) with no evidence of recent infection (ie, nucleocapsid antibody negative). Receptor binding domain (RBD) antibody titers were analysed (Elecsys Anti-SARS-CoV-2 assay;Roche Diagnostics, Basel, Switzerland) prevaccination, after 1 dose, and <4, 4-8, 8-12, and >12 weeks after full vaccination. Fisher's exact tests and regression models determined association with seroconversion and log2 antibody levels. Result(s): Demographics were similar between the mRNA and nonmRNA vaccine recipients (Table). Seroconversion (>=0.8 U/mL spike RBD antibody) occurred in 100% (80/80) of fully vaccinated mRNA recipients and 62% (18/29) of fully vaccinated non-mRNA vaccine recipients. Higher spike RBD antibody levels were seen with mRNA (grand mean: 512.6 U/mL, range: 1.3-4572.0) vs non-mRNA (grand mean: 39.3 U/mL, range: 0.4-368.5) vaccines at all time points studied. Vaccination with a non-mRNA vaccine predicted lower antibody levels (beta: -5.90 [95% CI: -6.99 to -4.82];P<0.0001) and less seroconversion (Fisher's exact: P<0.0001), whereas age, sex, body mass index, and absolute lymphocyte count (ALC) did not. Conclusion(s): Participants receiving ozanimod developed humoral immune response to SARS-CoV-2 vaccines, with 100% seroconversion after mRNA vaccination;this was independent of demographic characteristics and ALC levels at time of vaccination. However, some participants developed lower antibody concentrations and may benefit from booster doses. These findings provide important information for physicians managing ozanimod-treated patients with UC or MS.

Distressed Work: Chronic Imperatives and Distress in Covid-19 Critical Care.

This ethnographic study introduces the term "distressed work" to describe the emergence of chronic frictions between moral imperatives for health care workers to keep working and the dramatic increase in distress during the Covid-19 pandemic. Interviews and observant participation conducted in a hospital intensive care unit during the Covid-19 pandemic reveal how health care workers connected job duties with extraordinary emotional, physical, and moral burdens. We explore tensions between perceived obligations of health care professionals and the structural contexts of work. Key findings cluster around the moral imperatives of health care work and the distress that work engendered as work spaces, senses of vocation, patient and family interactions, and end-of-life care shifted. While the danger of working beyond limits has long been an ordinary feature of health care work, it has now become a chronic crisis. Assessing this problem in terms of distressed work and its structural contexts can better address effective, worker-informed responses to current health care labor dilemmas.

Serologic Response and Clinical Outcomes of SARSCoV-2 Infection and Vaccination in Ozanimod-Treated Participants With Relapsing Multiple Sclerosis

Introduction: Multiple sclerosis disease-modifying therapies, including sphingosine 1-phosphate receptor modulators, may attenuate the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. Objective(s): To describe the serological response and clinical outcomes of SARS-CoV-2 infection and vaccination in ozanimodtreated participants with relapsing multiple sclerosis (RMS) in an open-label extension (OLE) trial. Method(s): Participants with RMS who completed a phase 1-3 ozanimod trial could enter an OLE trial (DAYBREAK-NCT02576717) of ozanimod 0.92 mg/d. This analysis (January 2020-October 2021 [serology] and January 2022 [clinical outcomes]) included DAYBREAK participants who received SARSCoV-2 vaccines (fully vaccinated) and/or had COVID-19 adverse events. Receptor binding domain (RBD) antibody levels and nucleocapsid antibody positivity were analysed using Roche Elecsys assays. Log2 RBD antibody levels were compared between groups using t-tests. Result(s): Among the 148 vaccinated participants with serological data, 39 participants had serologically confirmed SARS-CoV-2 exposure. After full vaccination, RBD seroconversion occurred in 100% (n=39/39) of nucleocapsid antibody positive and most (n=98/109) nucleocapsid antibody negative participants (with 100% seroconversion in nucleocapsid antibody negative participants receiving mRNA vaccines [n=80/80]). Significantly higher RBD antibody levels were observed in the vaccinated nucleocapsid antibody positive vs negative vaccinated participants (median [range], U/mL: 2259 [12.4-44260.0] vs 138 [0.4-4572.0], respectively, P<0.0001). COVID-19 adverse events were reported in 15/148 participants, all nonserious events (confirmed=12, suspected= 3). Ozanimod treatment was continued in 9 participants and interrupted in 5 (1 unknown). Eleven participants recovered by the time of data cut off, and one recovered with sequelae (cough and loss of sense of smell). Conclusion(s): Participants with RMS receiving ozanimod mount a serologic response to SARS-CoV-2 infection and vaccination. COVID-19 events in these fully vaccinated participants were nonserious. A limitation of this research is its retrospective nature and the potential for selection bias towards higher-risk individuals.

COVID-19 vaccine uptake and hesitancy amongst Australian patients with breast cancer

Aims: Vaccination uptake is the principal focus of the world-wide response to the COVID-19 pandemic. Vaccine hesitancy remains a critical issue. Our aim was to ascertain rates and reasons for vaccine hesitancy in people with breast cancer (BC) in Australia. Method(s): Between June and October 2021, an anonymous online survey was conducted among people with solid organ cancer treated at nine Australian treatment centres. Data collected included demographics and clinical characteristics. Vaccine hesitancy and related beliefs were assessed using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale (OCVCCS), and the Disease Influenced Vaccine Acceptance Scale-Six. Descriptive statistics, chi-squared and linear regression were used. Results for the BC subgroup are reported. Result(s): The BC subgroup (N = 986, mean age 58.4 years, 99% female) comprised 36.6% of the responses in the solid cancer population (N = 2691). Most (76%) were treated at metropolitan centres and 64% were receiving ongoing treatment. Early BC was more commonly reported than metastatic BC (77% vs. 23%). Overall, 82% self-reported at least one COVID-19 vaccine dose. Unvaccinated participants were more likely to diagnosed with BC for a shorter time (<2 years (22.1%) vs >=2 years (14.5%), p = 0.003). Participants with metastatic BC were more likely to be unvaccinated and report greater disease-related vaccine concerns and hesitancy, when compared with participants with early BC (all p < 0.05). When compared with participants with all other solid cancers, participants with BC reported more negative attitudes towards COVID-19 vaccine side-effects (OCVCCS Side-Effects subscale mean scores: 5.19 (SD 1.91) vs. 5.46 (SD 1.82), p < 0.001). Conclusion(s):Despite a relatively high rate of self-reported vaccination, people with BC reported lower vaccine confidence when compared with all other solid cancers. A better understanding of these inequalities, and strategies to address vaccine confidence in people with BC, particularly those with metastatic BC, should be developed.

Exploring attitudes towards COVID-19 vaccination in adults with haematological malignancies

Aims: People with haematological malignancies (HM) are at increased risk of severeCOVID-19 infection and death due to underlying immune deficiency and impaired vaccine responses. FromMarch 2021,COVID- 19 vaccination was offered to patients with HM, as part of the Australian COVID-19 vaccination rollout program. This study sought to ascertain whether vaccine hesitancy was a barrier to optimal vaccine uptake and explored the attitudes of people with HM towards COVID-19 vaccination. Method(s): Between June and October 2021, an online survey was distributed to adults with HM at nine Australian health services. The survey collected sociodemographic and clinical characteristics, and attitudes towards COVID-19 and COVID-19 vaccination using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale, and the Disease Influenced Vaccine Acceptance Scale-Six (DIVAS-6). Result(s): Of the 869 survey participants (mean age 64.2 years, 43.6% female), 741 (85.3%) reported receiving at least oneCOVID-19 vaccine dose. Unvaccinated status was significantly associated with younger age, English as a non-dominant language, and shorter duration since diagnosis. Participants who were female or spoke English as their nondominant language reported more negative attitudes towards vaccine side-effects. Unvaccinated participants were more likely to report greater concerns about the vaccine impacting on their HM and treatment (DIVAS-6 Vaccine Vulnerability subscale score: B (SE) = 2.71 (0.35), p < 0.001). They were also more likely to report greater vaccine complacency (DIVAS-6 Disease Complacency subscale score: B (SE) = 1.79 (0.28), p < 0.001). Conclusion(s): People with HM reported high vaccine uptake, however, participantswho are recently diagnosed with malignancy, female, younger age or for whom English is a non-dominant language may benefit from targeted education strategies to address their vaccine concerns. Clinicians are well-positioned to address their patients' specific vaccine concerns and support the decision-making process, particularly with the need for COVID-19 vaccine boosters.

Achieving equitable access to cancer care and clinical trials in regional Australia: A networked approach to expand capacity and implement COSA teletrials model

Aim: Peoplewith cancer living in regional Victoria are less likely to participate in a clinical trial than metropolitan patients.We established a new geographically based trials network with the gaol of increasing the number of regional cancer patients recruited to clinical trials. Method(s): Initially six regional services and Cancer Trials Australia (CTA) collaborated to form Regional Trials Network Victoria (RTNV). Two more sites, Latrobe Regional Hospital and Mildura Public Hospital were added in 2021. This network represents a population of 1.9 million people and approximately 8000 new cancer diagnoses each year. Access to cancer clinical trials at regional sites was achieved by: Building capacity of regional clinical trial units Improving the efficiency of clinical trial conduct Implementing the COSA teletrial framework Investing in the capability of staff Increasing the number of clinical trials Results: In 2017, the CCV Clinical Trial Management Scheme (CTMS) recorded 1587 Victorians recruited to cancer clinical intervention trials. 428 resided in regional Victoria, but only 81 of these participated at a regional site, with others needing to travel. In 2017, 135 patients were recruited to RTN sites (regional plus Geelong) across 55 trials. By 2021, despite the impacts of the COVID19 pandemic the number of recruiting clinical trials increased by 54% and the number of regional patients recruited to CTMS studies in the network increased to 179. Driven by uptake of teletrials and registry trials total recruitment increased to 620 patients. RTNV leveraged funding to sustain core activity and was awarded $18.5 million from the Medical Research Future Fund to conduct health services research over the next 5 years. Conclusion(s): The RTNV is a successful implementation of a regionally based clinical trials network, improving access and participation of regional patients. Much of the increase was driven by the use of COSA Teletrials methodology.

CANCER SPECIFIC INFLUENCES ON VACCINATION ATTITUDE AND BEHAVIOR

Introduction People with cancer are particularly vulnerable to COVID-19 and have been prioritised in vaccination programs. This group has reported concerns regarding the interactions between vaccines, cancer and anti-cancer treatments. We explored vaccine hesitancy in the disease-specific context of cancer Methods An online survey was conducted in Australia from June to October 2021. We developed a six-item scale assessing vaccine concerns in the context of chronic disease (Disease Influenced Vaccine Acceptance Scale DIVAS-6). Results There were 2691 evaluable responses;59% female, 71% from metropolitan areas, 36% with metastatic disease and 56% on current anti-cancer treatment. Commonest cancer types included breast 36.6%, genitourinary 18.6% and gastrointestinal 18%. Self-reported vaccine uptake was 80%. Overall, 57% agreed with the statement 'cancer makes me more worried about being infected with COVID-19.' Their doctor's recommendation regarding the vaccine was considered important by 79% of participants. 67% agreed with the statement that 'cancer means having the vaccine is more important.' This was different between vaccinated and unvaccinated participants (72% vs 46%). Unvaccinated participants had more concerns regarding vaccine efficacy (60% vs 34%), side effects (72% vs 29%) and interactions with anticancer treatment (53% vs 18%). Conclusions People with cancer have disease-specific concerns regarding COVID-19 vaccines. Use of DIVAS-6 can guide communication in this medically vulnerable population.

EXAMINING COVID-19 VACCINATION STATUS AND VACCINE HESITANCY IN PEOPLE WITH BLOOD CANCERS

Introduction People with blood cancers are prioritised to receive COVID-19 vaccination. However, it is unclear how prevalent vaccine hesitancy is in this group. This analysis investigated vaccine uptake and vaccine hesitancy in people with blood cancers in Australia. Methods An online survey was conducted at nine health services in Australia from June to October 2021. Participant demographics and vaccination status were recorded. Vaccine hesitancy was assessed using the Oxford COVID-19 Vaccine Hesitancy Scale (OHS). Regression was used to examine whether clinico-demographic factors predicted the OHS score and vaccination status. Results Of the 869 participants, the mean age was 64.2 years, and 43.6% (n = 379) were female. A high proportion of participants had received at least one COVID-19 vaccine dose (85.3%, n = 741). Increasing age, speaking English as a first language, attending a regional health service, longer time since diagnosis and not currently receiving treatment were associated with being vaccinated. Participants who reported higher vaccine hesitancy were younger in age, more likely to have vocational qualifications and speak English as a second language. Conclusions There is a high rate of vaccination uptake in patients with blood cancers. However, younger patients and patients from culturally and linguistically diverse backgrounds appear to have lower vaccination uptake rates and higher levels of vaccine hesitancy. Tailored counselling may reduce the risk of adverse events due to COVID-19 infection.

At the intersection of harm reduction and COVID-19: the role of anthropologists during and post-pandemic

Harm reduction is a public health approach that emphasizes reducing the negative effects of drug use rather than eliminating it. It has been practiced for decades;however, the COVID-19 pandemic poses new challenges for people who use drugs (PWUD) and harm reduction providers. In the United States, public health recommendations to curb the pandemic are complicating harm reduction efforts. Harm reduction programs are rethinking how they engage with PWUD to comply with these recommendations while also providing essential services. In this article, we draw on academic literature, news articles, and information distributed by harm reduction programs to discuss issues currently faced by PWUD and harm reduction providers across the country. This discussion focuses on policy changes and programming adaptations related to three harm reduction interventions-syringe services programs, overdose prevention, and medications for opioid use disorder-that have emerged or gained traction during the pandemic. We argue that anthropologists should play a key role in addressing the obstacles and opportunities for harm reduction in the United States during and post-pandemic. Ethnographic research can generate important knowledge of how pandemic-related service and policy changes are localized by providers and experienced by PWUD and uncover how race. class, and gender may shape access to and experiences with modified harm reduction services. Applied anthropologists also have an important role in collaborating with harm reduction programs to ensure that the voices of marginalized individuals are not ignored as policy and programming changes take place during and after the pandemic.

Lower COVID-19 vaccination rates amongst Australians with gastrointestinal (GI) compared to other cancers

Background: People with cancer are at higher risk of serious illness and death from COVID-19 infection. We investigated the differences in COVID-19 vaccine uptake and attitudes in people with various solid organ and hematological malignancies. Methods: An online survey of adult patients with cancer attending eight health services across four states in Australia, was conducted from June to September 2021. Demographics, cancer history and vaccination status were recorded. Only completed surveys were analysed. Variables were compared with chi-squared and multivariable analysis using logistic regression. Vaccine hesitancy was assessed using the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford Vaccine Confidence and Complacency Scale, and the Monash Disease Vaccine Acceptance Scale. T-test analysis was used to examine relationships between the scales and groups. Results: There were 2997 evaluable responses;53.2% female, 61.8% from metropolitan areas, 27.5% with metastatic solid organ disease and 50.6% on current anti-cancer treatment. Patients with GI cancers comprised 13.5% (n = 405), compared with hematological 28.4%, breast 24.6%, genitourinary 14.1% and other cancer types 19.4%. Vaccination rates were significantly lower for respondents with GI cancers compared to other cancer types (71.6% v 79.3%;p< 0.001). Significant differences in the GI cancer population compared to all others were: more males (p < 0.001), lower level of education (p= 0.001), fewer reporting English as first language (p = 0.02) and shorter time since cancer diagnosis (p < 0.001). These remainedsignificant after logistic regression. Among GI cancer respondents, factors associated with being vaccinated compared to unvaccinated included: older age (p < 0.001), higher education level (p = 0.03) and English as first language (p = 0.01). There was no significant difference in the scales measuring vaccine hesitancy, confidence and complacency, for the GI cancer population compared to other cancers. As expected, there were significant differences in all scales comparing vaccinated to unvaccinated respondents with GI cancers. Conclusions: In our large, contemporary survey, Australians with GI cancers report lower COVID19 vaccine uptake compared with patients with other cancer types. We identified demographic and disease related characteristics that contribute to these differences. Interventions and targeted communication are required for people with GI cancers to maximise vaccination uptake in this medically vulnerable group.

Endovascular treatment of an unruptured ophthalmic artery aneurysm with a flow diverter: a case report

An unruptured aneurysm is often asymptomatic or present without neurological deficits, causing severe morbidity. However, the potential of this defect to rupture requires proper management. Herein, we report a case of an unruptured saccular aneurysm of the ophthalmic artery with initial clinical seizures. The patient was treated by flow diversion which redirects the blood flow that normally leads to the protrusion of the aneurysm back to the main vessel. Flow diversion is chosen because it is less risky and has a faster recovery time than other treatment options, but it is more expensive than others. Although this technology is not new, there is no report on its implementation in Indonesia. The patient was prescribed antiplatelet treatment for at least 6 months post-treatment, then she showed no sign of seizure or new focal neurological deficits 4 months post-treatment. The patients were expected to undergo digital subtraction angiography evaluation 6 months after flow diversion treatment, but it has not been performed due to the coronavirus disease 2019 pandemic.

COVID-19 outcomes in people with diabetes in Wales: a secondary analysis of the ABCD audit

Background: People with diabetes and coronavirus disease 2019 (COVID-19) have a significantly greater risk of death and/or intensive care unit (KU) admission. The Association of British Clinical Diabetologists (ABCD) recently audited out- comes for people hospitalised in the UK with diabetes and COVID-19. Methods: The ABCD COVID-19 and diabetes audit was a retrospective audit of patients admitted to UK hospitals with diabetes and COVID-19 between March and December 2020. Data related to patients admitted in Wales were compared with patients admitted in England and Scotland. Results: In Wales, 40/82 (48.7%) patients with diabetes had COVID-19-related mortality compared with 1,149/2,916 (39.1%) in the UK group (p=0.08). The Welsh cohort were more likely to be Caucasian, have a higher body mass index and HbA1c, be diagnosed with diabetic retinopathy and prescribed a sodium-glucose co-transporter 2 inhibitor or insulin than those in England and Scotland. Patients admitted to the ICU in Wales were more likely to be male and have type 2 diabetes. Conclusions: Patients admitted to hospital with diabetes and COVID-19 in Wales had a poorer outcome compared with England and Scotland. This disparity may reflect social inequality, differences in cardiovascular risk factors and/or differences in diabetes medications between hospitalised patients in Wales and the UK.

Physiotherapy experience of treating patients with PIMS-TR COVID-19 following stepdown from picu

Case report-IntroductionIt has been reported by the European Centre for Disease Prevention and Control that by May 2020 there were 230 suspected cases of PIMS-TR COVID-19. At Great Ormond Street Hospital NHS Foundation Trust (GOSH) there were 50 suspected cases. This report summarises the physiotherapy input to these patients outside of PICU. The rheumatology team were allocated the COVID-19positive ward and therefore were able to be involved in the evolving understanding of the clinical presentation and management of this new disease.Case report-Case description50 children were admitted to GOSH with suspected PIMS-TR COVID-19, of these, 36 were admitted to PICU. The mean length of stay in PICU was 4.6 days and the median 3.5 days (Range 1-16 days).The mean total length of stay in hospital was 11 days (range 2-94 days).42% were male and 57% female and the age ranged from 5 weeks-17 years, but the mean age was 9 yrs. Most were previously well, but 3 had asthma, 2 diabetes, 1 obese, 1 with liver disease and 2 with sickle cell disease.The physiotherapy provided included assessment and relatively quickly it was recognised that these patients had a specific pattern of muscle weakness (proximal>distal) and so the Manual Muscle Test of 8 muscle groups (MMT8) and the Childhood Myositis Assessment Score (CMAS) were adopted as outcomes. The initial mean MMT8 score was 56/80 (42-79) and mean CMAS score 20/52 (4-51)Assessment of respiratory function, mobility and safety of postural changes including sitting to standing, gait and managing the stairs was also included.The treatment provided included breathing exercises and specific muscle strengthening that was progressed as able. Advice to the nursing and medical staff was provided to ensure that patients were safe while they were regaining strength and stability. Gait re-education and stairs assessment was completed before discharge.The patients have now been placed into a multidisciplinary assessment programme to follow up the long-term outcomes including physiotherapy outcomes. At the 2 months follow up the mean MMT8 was 72/80 and the mean CMAS is 46/52 indicating that there may be a long-term impact upon musculoskeletal function in young people.Case report-DiscussionAt GOSH the rheumatology physiotherapy team were redeployed to the temporary general paediatrics service. This service was responsible for the patients who were diagnosed with this new and evolving disease and who were transferred from the PICU. The physiotherapy team started to recognise the extent of their illness including postural instability, muscle weakness, severe fatigue, and joint involvement. The children also had impairment in respiratory function and cardiac function. It was recognised that mobility was limited for many reasons and care was required in the intensity and frequency of exercise and level of activity. Initially moving around the bed was exhausting and had to be effective and safe before progressing to weight-bearing and walking.Because the physiotherapy team were musculoskeletal specialists, they were able to consider different outcome measures and quickly decided upon using the MMT8 and the CMAS as well as assessing joint range of movement and muscle length. Respiratory assessments were also completed.It was also recognised that as the hospital had rapidly developed the COVID-19ward (Hedgehog ward) and as the staff were from many different areas of the hospital effective communication between this new team had to be established and within weeks a daily MDT meeting was started that ensured all aspects of each patients care were discussed to enable complete co-ordinated treatment of the patient. This meeting allowed staff to contribute to decisions about treatment as well as ensuring the nursing staff were informed about safety for each child regarding mobility. The meeting also allowed for discharge planning to ensure that every child was safe to be discharged and was able to physically manage at home. A weekly psychosocial meeting was also developed and so the psychological and social f ctors for each child and their family could also be considered and supported.Case report-Key learning pointsThe hospital planned and prepared for the Pandemic and staff were placed together to work in different ways. Because of the diversity of the skills of the staff it was possible to recognise the many systems that were affected by the disease and to pull together the expertise of the staff to be able to provide a high level and holistic clinical management for each and every child. It has also been possible to explore outcome measures and to be able to work with each other and to learn and discuss treatments moving forwards.The speed in which a completely new service was established was impressive especially as there had been a misunderstanding initially that children would probably not be severely affected by COVID-19.The importance of physiotherapy treatment in order to enable these young people to regain strength, mobility and function was apparent and with the longer term follow up it is demonstrating that several of these patients need longer term care and treatment after discharge.The outcome measures that are being used for the longer term follow up;CMAS, MMT8, 6 min walking test as well as neurological examinations and questionnaires to assess function and psychological well-being and fatigue are able to be used if other patients develop this disease and these measures can be used nationwide in order to enable a cohesive approach to managing PIMS-TR COVID-19.