Infrastructures for Virtual Volunteering at Online Music Festivals

Volunteering benefits recipients, volunteers, communities, and society, while digital technologies establish new opportunities for virtual volunteering. We describe how volunteers transitioned the UK's long-established Oxjam grassroots music festival online in response to the COVID pandemic, delivering a local pilot before scaling up nationwide. We adopt an infrastructural perspective to reveal how two teams of volunteers defined a flexible festival format, knitted together diverse technologies into a technical platform, and operated this to deliver the festival. We highlight the need for teams of volunteers to orchestrate both audience and performer trajectories through festivals. We argue for deliberately designing in volunteer labour rather than automating it out by translating traditional roles online while defining new digital ones. We propose to make these roles rewarding through a more social volunteer experience, including privileged backstage access. We highlight the challenges of using social media for such events, including complying with algorithmic policing of rights. © 2023 Owner/Author.

Water Soluble Tocopherol Derivatives Inhibit the SARS-CoV-2 RNADependent RNA Polymerase

Rationale The recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic of the severe disease COVID-19 in humans. While efforts to quickly identify effective antiviral therapies have focused largely on repurposing existing drugs, the current standard of care, remdesivir, remains the only authorized antiviral intervention of COVID-19 and provides only modest clinical benefits. Thus, new antivirals targeting SARS-CoV-2 are urgently needed. Methods Artificial intelligence algorithm MediKanren was used to query FDA-approved and late-stage drug compounds for potential interactions with SARS-CoV-2 proteins, coronaviruses, and host cell networks for possible antiviral activity. From this, 157 compounds were further tested in an antiviral screen against live SARS-CoV-2 for reduction in viral growth. Select compounds were further assessed for synergistic activity with remdesivir. Both in vitro and cell free systems identified tocopherol succinate compounds that inhibited the RNA-dependent RNA polymerase (RdRp). Validation of antiviral and synergistic activity was performed in primary human airway epithelial cell cultures against multiple SARS-CoV-2 variants.Results Here we show that water-soluble derivatives of α-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 (RdRp). Through an artificial-intelligence-driven in silico screen and in vitro viral inhibition assay, we identified D-α-tocopherol polyethylene glycol succinate (TPGS) as an effective antiviral against SARS-CoV-2 and β-coronaviruses more broadly that also displays strong synergy with remdesivir. We subsequently determined that TPGS and other water-soluble derivatives of α- tocopherol inhibit the transcriptional activity of purified SARS-CoV-2 RdRp and identified affinity binding sites for these compounds within a conserved, hydrophobic interface between SARS-CoV- 2 nonstructural protein 7 and nonstructural protein 8 that is functionally implicated in the assembly of the SARS-CoV-2 RdRp. Conclusion In summary, solubilizing modifications to α-tocopherol allow it to interact with the SARS-CoV-2 RdRp, making it an effective antiviral molecule alone and even more so in combination with remdesivir. These findings are significant given that many tocopherol derivatives, including TPGS, are considered safe for humans, orally bioavailable, and dramatically enhance the activity of the only approved antiviral for SARS-CoV-2 infection.

Erosion of Inflatable Penile Prosthesis with Prolonged Foley Catheterization in the COVID-19 Era

Introduction: The COVID-19 pandemic has changed the lives of many in the past year. As of writing this article, the virus has claimed over half a million American lives and has infected millions more. It has affected many people regardless of age, gender, race, religion, or medical history. We have noticed a unique sequence of events in urology patients with a prior history of inflatable penis prothesis implantation who have gotten critically ill from the SARS-CoV-2 virus. Objective: We report our experience with patients with an inflatable penile prothesis who suffered respiratory failure due to the SARS-CoV-2 virus and findings that would help limit the risk of implant infection and/or erosion if prolonged urethral catherization is needed. Methods: We have encountered 3 patients with a very similar history in the past year. They were all men aged 57-72 years old who had a functioning inflatable penile prothesis (IPP) for many years (3-13) and were intubated for a prolonged period of time (2-4 weeks) after suffering respiratory distress from the SARS-CoV-2 virus. During this time, they all had a prolonged urethral Foley catherization for urinary drainage while in the ICU. They were all subsequently found to have urethral erosion of a penile implant cylinder which was not present prior to hospitalization. Their charts were reviewed. Results: Two patients underwent explantation of their IPP during their hospital stay and one presented to our outpatient office 2 months after discharge with the complaint of urethral cylinder erosion and underwent subsequent explantation. Conclusions: Urethral catheterization is commonly used in the intensive care unit and spinal cord injury patients due to their convenience and efficacy. The friction and inflammation created by prolonged transurethral catheterization can be disastrous for IPPs by increasing the likelihood of infection and/or device erosion. In fact, Steidle and Mulcahy found that five out of their nine patients (55%) with IPPs who had an indwelling or intermittent transurethral catheterization were eventually found to have erosion of their IPP. In addition, indwelling transurethral catheters also confer a higher risk of urinary tract infection. Han et al. found that suprapubic tube placement conferred a statistically significantly lower risk of urinary tract infection when compared to indwelling transurethral catheterization for over five days at an odds ratio of 0.142 (95% CI 0.073-0.0276). Another alternative to bladder drainage in the intubated IPP patient is clean intermittent catherization (CIC), however this poses a unique challenge in the intubated COVID positive patient as it repeatedly exposes healthcare staff the virus-carrying patient. When compared to indwelling transurethral catherization, suprapubic tube placement has been shown to confer a lower risk of urinary tract infection and IPP infection/erosion. This can primarily be explained by its ability to drain the bladder without creating inflammation and friction in the urethra. Therefore, we propose that any team caring for a patient with an IPP and a planned, prolonged indwelling transurethral catheterization consult urology services to have a suprapubic tube temporarily placed. This will ensure that the risk of urinary tract infection and/or IPP erosion is kept as low as possible. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Boston Scientific, Neotract

A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss.

BACKGROUND: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. METHODS: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. RESULTS: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. CONCLUSIONS: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

Sars-Cov-2 Antibody Decay Monitoring in mRNA Vaccinated Multiple Myeloma Patients

Introduction: Amid the current COVID-19 pandemic, the highest mortality rates are among the elderly and immunocompromised. Multiple myeloma (MM) patients are immunocompromised and often are elderly. Not only do MM patients develop more frequent infections, but it is one of the leading causes of death for these patients. This population develops more severe COVID-19 due to various mechanisms that impair their ability to fight infection. This also reduces their ability to generate immunity from vaccination, as has been demonstrated by their diminished responses to vaccines for various respiratory illnesses. It follows that while phase III trial results for mRNA1273 and BNT162b2 COVID-19 vaccines showed an efficacy of 94-95% against even mild infection with this virus, the efficacy has been shown to be lower among MM patients. We recently evaluated patients' antibody responses to vaccination for COVID-19 by measuring anti-spike IgG levels in patient serum from before vaccination (baseline) and two weeks after dose 2 (D2W2) of vaccination with mRNA-1273 or BNT162b2, and found that most MM patients have impaired responses (Stampfer et al., Leukemia 2021). Patients who received mRNA-1273 vaccine had higher antibody levels than those who were vaccinated with BNT162b2, and specific clinical and myeloma-related characteristics predicted vaccine responsiveness. In the current study, we are monitoring anti-spike IgG antibody levels at Dose 2 Week 8 (D2W8) and Dose 2 Week 16 (D2W16) post-mRNA vaccination among these patients and in age-matched healthy controls to investigate antibody decay. Methods: Participants in the trial included MM patients (n=91) at the Berenson Cancer Center, and age-matched healthy controls (n=27). Healthy subjects were not known to be immunocompromised or currently receiving immunosuppressive therapy. Vaccination was done outside of the clinic and subjects provided copies of their CDC-issued COVID-19 vaccination cards to confirm dosing dates. Sera from vaccinated individuals were drawn at baseline (0-60 days prior to first vaccine dose) and at intervals following their second dose (14-21, 56-70, and 112-126 days post-vaccination). Background levels were determined from the clinic's serum bank of healthy subjects drawn pre-April 2019. Using an ELISA-based assay that detects IgG antibodies to SARS-CoV-2 spike protein, we determined Anti-SARS-CoV-2 spike ectodomain serum antibody levels and quantified them in IU/mL based on the WHO International Standard 20/136. Results: We analyzed the patient and control populations, and specifically for those classified as responders from our original published study (D2W2 >50 IU/mL). All controls but only 70% of patients (64/91) were classified as responders, so this responder-specific analysis was only relevant for patients. There was a significant decline in anti-SARS-CoV-2 spike antibodies from D2W2 to D2W8 for both patients and controls;D2W16 results are pending. Median values dropped from 283.1 IU/mL to 90.9 IU/mL among patients, and 893.6 IU/mL to 354.4 IU/mL among controls. Median antibody levels among patients classified as responders dropped from 482.9 IU/mL to 145.5 IU/mL (p <0.0001). We also found that the D2W8 value for patients was significantly lower than that of controls (90.9 IU/mL vs 354.4 IU/mL, p<0.0001), as well as among the responder group (145.5 IU/mL vs 354.4 IU/mL, p=0.0005). A cutoff of <147 IU/mL has previously been associated with an increased risk for breakthrough infections. Spike antibody levels of 50% of patients who responded and 64.8% of all patients were <147 IU/mL at D2W8, whereas only 7.4% of controls were <147 IU/mL (p<0.0001). Conclusions: The markedly lower anti-spike antibody levels among MM patients compared to healthy controls at week 8 post-vaccination indicate that they remain at high risk for breakthrough infections. Combined with their rapid decline in anti-spike antibody levels over only a 6-week period, this indicates that even MM patients who responded initially to vaccination are likely to require boosters sooner tha healthy individuals. This immunocompromised population remains at high risk even following vaccination and should continue to maintain social distancing precautions during periods of high local SARS-CoV-2 transmission. Disclosures: No relevant conflicts of interest to declare.

Assessment of sleep disturbances in children and adolescents with inflammatory bowel disease

Background: Poor sleep has been well described in the adult inflammatory bowel disease (IBD) population. Few studies in the pediatric population have demonstrated a similar relationship. The aim of this study was to assess the prevalence of sleep disturbances and sleep-related daytime impairments in children and adolescents with IBD. Methods: This pilot, prospective cross-sectional study included pediatric IBD patients seen in the GI clinic or infusion center at The American Family Children's Hospital in Madison, Wisconsin between February and April of 2021. Patients completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Sleep Disturbance-Short Form and Pediatric Sleep-Related Impairment-Short Form questionnaires at the time of their visits. The questionnaires assessed difficulties with sleep at night, and daytime symptoms associated with poor sleep. The disease activity was scored using the Abbreviated Pediatric Crohn's Disease Index (PCDAI) for Crohn's Disease and the Pediatric Ulcerative Colitis Activity Index (PUCAI) for Ulcerative and Indeterminate Colitis. Demographics, disease-related information, and laboratory data within the past 6 months from time of the patient visit were acquired from medical charts. Iron deficiency was determined by ferritin <30 ng/mL or iron saturation <20% with a normal CRP or ferritin <100 ng/mL with an elevated CRP. Vitamin D deficiency was determined by 25-hydroxy-vitamin D ≤30 ng/mL. All data was analyzed using Fisher's exact test and a p-value <0.05 was used to define statistical significance. Results: Forty-four patients (mean age 14.7, SD 2.8) with IBD (68.2% with Crohn's Disease, 25.0% with Ulcerative Colitis, 6.8% with Indeterminate Colitis) were enrolled. Of those with Crohn's Disease, 73.3% had inactive disease and 26.6% had active disease based on PCDAI score. For those with Ulcerative and Indeterminate Colitis, 57.1% were in remission and 42.8% had active disease based on PUCAI scores. Of all patients, 29.6% had some degree of sleep disturbance and 50.0% had sleep-related daytime impairments. Additionally, 13.6% of patients were currently taking a sleep medication and 20.5% had been on oral steroids within the last 3 months. Among the patients, 44.2% had iron deficiency and 61.9% had vitamin D deficiency. Patients with active disease reported more sleep disturbances (43% vs 23%, p=0.2878) and sleep-related daytime impairments (71% vs 40%, p=0.0520), however the results were not statistically significant. Patients with vitamin D deficiency reported fewer sleep disturbances than those with no vitamin D deficiency, which was statistically significant (19% vs 50%, p=0.0472). There was no significant difference in sleep-related daytime impairments between those groups (38% vs 69%, p=0.1109). Statistical analysis showed that age, iron deficiency, and current/recent use of oral steroids were not significantly correlated with sleep disturbances or sleep-related daytime impairments. Conclusions: Despite the previously reported correlation between IBD and sleep, our pilot study does not demonstrate a strong correlation between sleep disturbances and disease activity. However, this relationship may be shown among a larger patient population than seen in this study. There was a higher prevalence of sleep-related daytime impairments rather than sleep disturbances among all enrolled IBD patients. This could reflect the overlap between sleepiness and fatigue as these are difficult to distinguish. In addition, there are numerous cofactors that can cause sleep problems in pediatric patients. These include variables such as age, oral steroids, iron deficiency, and vitamin D deficiency. To our surprise, our patients with vitamin D deficiency reported better sleep compared to patients with normal vitamin D levels;however, vitamin D levels were obtained anywhere up to 6 months prior to sleep questionnaire completion. Sample size of the study was limited due to a 2-month data collection period, and the ongoing COVID-19 pandemic restricting in-person visi s. Other limitations include the accurateness of self-reported answers on the sleep questionnaires and the time variability between laboratory values and administration of the sleep questionnaires. Future research may be helpful to further study sleep issues in pediatric IBD patients.

COBRE on Opioid and Overdose: A Collaborative Research-Based Center Addressing the Crises in Rhode Island and Beyond

Overdose deaths across the country have spiked since the onset of the COVID-19 pandemic. It is crucial now, more than ever, to address the continuing and worsening, complex and dynamic opioid and overdose epidemics. In 2018, The Center of Biomedical Research Excellence (COBRE) on Opioids and Overdose, based at Rhode Island Hospital, launched with three major goals: 1) establish a center of scientific excellence on opioids and overdose;2) train the next generation of scientists to become independent investigators and address the opioid and overdose crises;and 3) contribute to the scientific progress and solutions to combat these epidemics. To date, we have made substantial progress. While the opioid and overdose crises continue to evolve, the COBRE on Opioid and Overdose and its team of investigators are well poised to address the daunting task of understanding and meaningfully addressing these deadly epidemics, with the ultimate goal of saving lives.