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Background: Targeted Immune-Modulating Therapies (TIMT) and immunomodulators (IMM) for Immune Mediated Inflammatory diseases (IMID) theoretically interfere with humoral responses against COVID19. However, IMID patients and particularly patients receiving immunosuppressive treatment were excluded from phase-3 COVID19 vaccination efficacy trials. Real-world observational data is therefore required to provide more insight into the efficacy of COVID19 vaccination in IMID patients. Method(s): The BELCOMID study is a multidisciplinary, prospective observational cohort study performed at two university hospitals and set up with the intention to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort. Consecutive patients seen between 17/12/2020 and 28/02/2021 during routine follow-up for IMIDs of the gut, joints and skin were invited to participate. Both patient data and serological samples were collected at 3 predefined periods (Figure 1: Before vaccination, after start of the national vaccination campaign before booster vaccination, after booster vaccination). Spike (S) protein antibodies were analysed with the Abbott ArchitectTM assay. R version 4.0.2 was used to perform analyses. Result(s): At inclusion period 2, 2065 patients (Table 1) participated of whom 1547 had received complete baseline vaccination (2 doses mRNA-1273, BNT162b2, ChadOx1 nCoV-19 or 1 dose JN78436735). S-antibody seroconversion rate was 91.2%. At inclusion period 3, data was available for 1566 patients of whom 74.7% had received 1 booster (BNT162b2 or mRNA-1273) vaccination leading to a S-antibody seroconversion rate of 98.3%. In 130 patients who had received 2 boosters, S-antibody seroconversion rate was 100%. At period 3, 37 patients had refused all vaccinations. Although 23 of these had experienced confirmed COVID19 since previous inquiry, no S-antibody seroconversion was found in 15 of them. Logistic regression analyses revealed that the odds of no S-antibody seroconversion were significantly higher in IMID patients treated with IMM, combination of IMM+TIMT, systemic steroids and smoking patients at both inclusion periods (Table 2). TIMT monotherapy did not influence seroconversion rates at inclusion period 3 but was associated with higher odds of the lowest S-antibody titre quartile (OR2.32, P<0.001). Among TIMT options, rituximab had higher odds of S-seronegativity. Conclusion(s): S-antibody seroconversion rate in this real-life IMID population was high after baseline vaccination and increased further proportionally with booster vaccination, highlighting the value of repeated vaccination. However, the serologic response may be blunted due to different IMID treatment modalities and smoking.
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Background. Long COVID is a heterogenous condition. We previously demonstrated distinct phenotypes of long COVID, but the impact of later waves caused by SARS-CoV-2 variants on long COVID presentations has not been described. Methods. We selected individuals with ongoing symptoms > 4 weeks from PCR-confirmed COVID-19 in a multicentre, prospective cohort study. We used multiple correspondence analysis and hierarchical clustering on self-reported symptoms to identify symptom clusters, in individuals recruited during two periods;cohort 1 from March 2020 to April 2021, and cohort 2 from April 2021 to March 2022. We explored differences in symptoms by mapping acute infection to one of four COVID-19 waves in Ireland (table 1) as well as vaccination status, and used Chi2 test to compare symptoms frequencies. Results. Demographics are shown in Table 2. Cluster analysis of each cohort demonstrated 3 distinct clusters in both cohorts, which shared similar clinical characteristics;a musculoskeletal/pain symptom cluster, a cardiorespiratory cluster and a third less symptomatic cluster (Figure 1). While symptoms within clusters were similar across both periods, in the cardiorespiratory cluster, the frequency of palpitations decreased (56% vs 16%) and cough increased (14% vs 45%) between reporting periods (both P< 0.01). Furthermore, a greater proportion of palpitations were reported in those with COVID-19 from waves 1 and 2 (35% and 28%) compared to 3 and 4 (both 12%, P< 0.001), and a greater proportion of chest pain in waves 1, 2 and 4 compared to wave 3. There were no differences in other symptoms (Table 3). Additionally there were significantly less palpitations reported in those vaccinated at the time of review (17% vs 31% P=0.002), but not chest pain (30% vs 39% P=0.13). In multivariate analysis, infection in wave 3 and 4 but not vaccination status remained significantly associated with lower reported palpitations (OR (95% CI) 0.28 (0.13-0.97) and 0.5 (0.06-0.87) for waves 3 and 4, both P< 0.05), and wave 3 infection remained independently associated with lower reported chest pain (OR 0.3 (0.25-0.7)). Conclusion. Three symptom clusters define long COVID across the two cohorts, but characteristics of the cardiorespiratory phenotype have evolved over time with evolution of SARS-CoV-2 variants. (Table Presented).
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SESSION TITLE: Critical Care in Chest Infections Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: During the COVID-19 pandemic, acute respiratory distress syndrome (ARDS) was a very common presentation. Many clinicians sought to rule out COVID-19 in those presenting with hypoxia and shortness of breath due to the importance of triage and quarantining infected individuals and those under investigation. As a result, delay in diagnosis of other viral and bacterial pathogens occurred. There is a known but rare overlapping of disease processes and sometimes even co-infections with COVID-19 and Pneumocystis jirovecii pneumonia (PJP) which made narrowing the differential challenging [1,2]. We present a case of a patient with known HIV who presented with typical features of COVID-19 and clinically worsened. Further investigation revealed PJP and AIDS. CASE PRESENTATION: A 55-year-old female with a past medical history of human immunodeficiency virus (HIV), previously controlled on highly active antiretroviral therapy (HAART), presented with shortness of breath, cough, and syncope. She required sedation and mechanical ventilation following significant hypoxia on admission. Chest radiograph and computed tomography (CT) were concerning for acute respiratory distress syndrome (ARDS) with diffuse bilateral ground glass opacities (Figure 1 and Figure 2) and she was found to be in septic shock requiring vasopressors. She presented during the COVID-19 pandemic and it was initially thought to be the cause of her condition, however she repeatedly tested negative via polymerase chain reaction (PCR). Through further investigation, it was found that her total cluster of differentiation 4 (CD4) cell count was 184/??L, posing a risk for opportunistic infections. Prior records indicated her last CD4 count was greater than 250/??L. Bronchoscopy showed progressively darker-tinged aliquots significant for diffuse alveolar hemorrhage that stained positive for Pneumocystis jirovecii pneumonia (PJP). She was treated with appropriate antimicrobial therapy, eventually weaned from ventilation, and transferred to the floor despite her high risk of morbidity and mortality [3]. DISCUSSION: This clinical case demonstrates PJP infection in an individual with features on imaging nearly identical to those of COVID-19 during the pandemic. There is a strong role in verifying CD4 count and HIV viral level in those affected with HIV with reported medication adherence who present with critical illness. There should be a low threshold to perform bronchoscopy in patients with ARDS and negative COVID-19 if no known source is identified. CONCLUSIONS: It is important to consider all causes of ARDS in patients who are immunocompromised with a low threshold to test for and treat uncommon causes, such as opportunistic infections, because the treatment should be directed at the underlying cause. Reference #1: Coleman, H., Snell, L., Simons, R., Douthwaite, S. and Lee, M., 2020. Coronavirus disease 2019 and Pneumocystis jirovecii pneumonia: a diagnostic dilemma in HIV. AIDS, 34(8), pp.1258-1260. Reference #2: Menon, A., Berg, D., Brea, E., Deutsch, A., Kidia, K., Thurber, E., Polsky, S., Yeh, T., Duskin, J., Holliday, A., Gay, E. and Fredenburgh, L., 2020. A Case of COVID-19 and Pneumocystis jirovecii Coinfection. American Journal of Respiratory and Critical Care Medicine, 202(1), pp.136-138. Reference #3: Dworkin, M., Hanson, D. and Navin, T., 2001. Survival of Patients with AIDS, after Diagnosis of Pneumocystis carinii Pneumonia, in the United States. The Journal of Infectious Diseases, 183(9), pp.1409-1412. DISCLOSURES: No relevant relationships by salah alandary No relevant relationships by Joella Lambert No relevant relationships by Joshua Lung
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Purpose : Anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections are efficacious treatments for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), but optimal real-world outcomes require frequent treatment and monitoring that can be burdensome to patients and hinder their ability or willingness to follow their management plan. This study aimed to understand patient treatment experience with anti-VEGF standard of care. Methods : This observational study employed a cross-sectional quantitative survey comprising de novo questions, patient-reported outcome (PRO) measures and medical chart extraction. Adult patients in the USA, UK and Canada with nAMD or DME, and treated with anti-VEGF injections for ≥12 months, were recruited via 21 (9 USA, 6 UK, 6 Canada) clinical sites. Results : Between January and August 2021, 148 (67 USA, 33 UK, 48 Canada) DME and 219 (98 USA, 54 UK, 67 Canada) nAMD patients completed their surveys. While 159 (43%) patients had a study eye visual acuity at most recent reading >70 approxETDRS letters, PRO scores indicated that patients across the two conditions had relatively high visionrelated functioning (NEI-VFQ-25) and were generally satisfied with their current treatment (MacTSQ and RetTSQ). Eighteen DME patients (12%;12% in the US, 27% in the UK, 2% in Canadian samples) and 9 nAMD patients (4%;3% USA, 3% UK, 4% Canada) missed at least 1 injection visit in the past 12 months. Reported barriers were mainly related to treatment, clinic and appointment factors, and the COVID-19 pandemic. Half of the patients reported some level of impairment in their daily activities due to the treatment. Following treatment, the majority recovered within 1 day;however, a sizable portion (24%;21% USA, 31% UK, 22% Canada) needed >1 day to recover. Among the working patients (N = 55), 34 (62%;58% USA, 67% UK, 65% Canada) reported some level of productivity impairment in the form of absenteeism. Conclusions : Despite high adherence and treatment satisfaction levels, patients reported impairment of daily activities, burden, and barriers related to treatment. In general, more DME patients missed at least 1 visit than nAMD patients. More durable treatments with longer intervals could further reduce treatment burden and address the current barriers faced by patients.
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Purpose : Patients on systemic immunomodulatory therapy (IMT) for uveitis are at higher risk of infection and infectious complications. While other medical specialties have studied the safety of IMT in non-ocular, autoimmune conditions vis-à-vis coronavirus disease 2019 (COVID-19), little is known about the effects of these drugs in uveitis patients specifically. The objective of this study was to determine if uveitis patients with COVID-19 were at higher risk of hospitalization for this pandemic illness and whether systemic IMT affected this risk. Methods : Retrospective cohort study of uveitis patients in 2020 in the United States. The Symphony health insurance claims dataset was used. Inclusion criteria were an ICD10 code for COVID-19, a code for any form of non-infectious uveitis or scleritis, and age 18 or greater. Drugs studied included methotrexate, mycophenolate, azathioprine, tacrolimus, cyclosporine, adalimumab, infliximab, tocilizumab, rituximab, and JAK, IL-17, and IL-12/23 inhibitors. The main outcome measure was adjusted odds of hospitalization for COVID19. Multivariable logistic regression was used to adjust for major risk factors for severe COVID-19 disease, including age, biological sex, cardiac, pulmonary, hepatic, and renal disease, obesity, organ transplant, stroke, and certain cancers. Results : 3,974,272 patients in the dataset were diagnosed with COVID-19 in 2020. Of these, 6389 (0.16%) had established diagnoses of uveitis or scleritis. Within the uveitis group, mean age was 54 years (SD 16), and 62% were female. 708 (11.1%) of the uveitis patients were hospitalized for COVID-19, significantly greater than the 7.3% rate amongst all adult, COVID-19-positive patients in the dataset (p < 0.001) and the CDC estimate of 7.5% for the US population in 2020 (p < 0.001). No agent showed a statistically significant effect on hospitalization. The higher rate of hospitalization in uveitis patients was partly, though not completely, explained by higher rates in uveitis-associated autoimmune conditions in the dataset as a whole. Conclusions : Uveitis patients have a greater risk of hospitalization for COVID-19 compared with the general population. As a whole, conventional IMT and biologics do not increase the risk of COVID-19 hospitalization amongst uveitis patients infected with the virus.
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Objectives: Optimal real-world outcomes in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) require frequent and potentially burdensome visits for patients and their caregivers. This study aimed to understand the caregiver perspective on treatment burden, barriers and the impact of caregiving, with a particular focus on the demands of frequent anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection treatment. Methods: Caregivers of adult nAMD/DME patients treated with anti-VEGF injections were enrolled from 21 clinical sites in the USA, UK and Canada. Caregivers completed a cross-sectional survey comprising de novo questions and a self-reported outcome instrument. Results: Overall, 18 DME and 44 nAMD caregivers completed surveys. On average, caregivers provided care 4.3±3.0 days/week, 4.0±4.3 hours/day. Caregivers reported supporting patients on a diverse array of tasks including transportation to doctors' appointments, providing emotional support, and helping with shopping and household chores. Twelve (67%) DME and 30 (68%) nAMD caregivers reported at least one barrier that prevented patients from receiving treatment or attending visits. Barriers were mainly related to the COVID-19 pandemic restrictions, particularly preventing caregivers from accompanying patients to appointments, clinic/appointment factors (distance, difficulty in scheduling appointments, other medical appointments priority, appointment duration), and social/health related factors (caregiver’s availability, care recipient’s reduced mobility/physical limitations). Overall, 13/22 (59%) working caregivers reported an impact on work absenteeism due to helping with treatment appointments. Based on the Caregiver Reaction Assessment scores, caregivers experienced a moderate impact on schedule disruptions, and a milder impact on financial problems, lack of family support, health and self-esteem in relation to their caregiving situation. Conclusions: Caregivers devote significant time to caring for the recipient, with the greatest impact on caregiver schedule disruptions and absenteeism for those working. More durable treatments with longer intervals and fewer appointments may alleviate some of that burden.
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Introduction: BICSTaR (GS-EU-380-4472/GS-CA-380-4574/GS-IL-380- 5335) is an ongoing, multinational, observational cohort study evaluating real-world effectiveness and safety of B/F/TAF in ART naïve (TN) and ARTexperienced (TE) PLWH. Materials and Methods: This 12M pooled analysis included PLWH starting B/F/TAF in clinical practice from June 2018 to September 2020 (latterly during the COVID-19 pandemic) in Europe/Israel/Canada. Outcomes included virological effectiveness (HIV-1 RNA <50 copies/ml [missing=excluded]), persistence, drug-related adverse events (DRAEs), and laboratory parameters. Results: One-thousand one hundred thirty-five PLWH were included (Table 1). The TE group had older median age than TN. Of TE participants, 65%/20%/16% switched from INSTI/NNRTI/PI-based regimens (36% TDF/46% TAF/13% ABC);12% had prior virologic failure. Baseline resistance was documented in 124/535 participants (NRTI/NNRTI/PI/ INSTI=6%/6%/3%/0.2%). Prevalence of comorbidities (47%/72% TN/TE) and concomitant medication usage was high. At 12M, 97% (149/154) of TN and 96% (771/800) of TE participants had HIV-1 RNA <50 copies/ml, and persistence on B/F/TAF was high [91% (1032/1135)]. In a multivariable analysis, TE participants with neuropsychiatric disorder ongoing at baseline had lower odds for viral suppression (odds ratio=0.45, 95% CI: 0.21-0.96). There was no emergence of resistance to the components of B/F/TAF. DRAEs occurred in 13% (148/1135) of participants;gastrointestinal and neuropsychiatric DRAEs were the most common (3% each). Discontinuations due to DRAEs were low (TN 4%;TE 6%). Serious DRAEs were rare (0.2%;2 TE participants with depression). Lipidchanges are shown (Figure 1). Conclusion: B/F/TAF was associated with high levels of effectiveness and persistence after 12M in this large real-world cohort of TN and TE PLWH with a high comorbidity burden. Effectiveness was demonstrated across key subgroups (females, older participants, late presenters). Importantly, there were no new or unexpected safety findings. Collectively, these real-world data continue to support the use of B/F/TAF in clinical practice.
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Aims To describe readmissions of hospitalised patients with COVID-19, define predictors of readmission and explore the long term outcomes using the SF-12 score compared to patients who were not readmitted and those not hospitalised. Methods A single centre retrospective in North Inner-City Dublin. Recruitment was done through a COVID follow up clinic. Predictors of readmission and SF-12 scores at two timepoints post follow up at median 3 months and 12 months. Results Seventy (45%) participants were admitted, with a median age of 49.5 years (IQR 41.3-56.9), 36(51%) of whom were female. Unscheduled readmissions at ≤30 days in COVID-19 patients were 9(12.9%) and length of stay was four days (IQR 2-5). Readmissions were due to ongoing symptoms(n=9(64.3%)) or new complications(n=5(35.7%)). Mechanical ventilation and having symptoms of nausea and vomiting on index admission were predictive of readmission. (p=0.002). SF-12 scores at one year of readmitted patients were not different to patients who were never admitted at median one year follow up, p=.089. Conclusions Most readmissions were of short duration. Early follow up of patients post MV or who had nausea and vomiting on index admission should be prioritised. Wellbeing of readmitted patients was not different to those never hospitalised, at one year.
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COVID-19 , Adult , Female , Humans , Male , Middle Aged , Nausea , Patient Readmission , Retrospective Studies , Risk Factors , VomitingABSTRACT
Background: Although presence of SARS-CoV-2 neutralising antibodies can provide protection against development of COVID-19, how reflective circulating anti-SARS-CoV-2 antibody levels are of underlying neutralising capacity, and whether a threshold exists to predict sufficient neutralising capacity remains unclear. Methods: In plasma from individuals with PCR-confirmed COVID-19 recruited to the All Ireland Infectious Diseases Cohort Study, we measured IgG concentrations against RBD, Spike protein sub-unit 1 and 2 (S1, S2) and Nucleocapsid (NC) using multiplex electrochemiluminescence (normalised to World Health Organisation reference serum as IU/mL). Neutralising capacity was measured against live SARS-CoV-2 virus (clinical isolate 2019-nCoV/Italy-INMI1) by determining the maximum plasma dilution required to maintain 50% inhibition of infection of Vero E6 cells (50% Neutralisation Titre (NT50)), by flow cytometry-based micro-neutralisation assay. Given that the Beta SARS-CoV-2 variant of concern (VOC) reduces neutralising activity up to six fold, we estimated a NT50 of 1:1000 against wild type SARS-CoV-2 would maintain neutralising activity against VOC. We used Spearman correlation and linear regression to model relationships between NT50 and IgG concentrations. Data are presented as median (IQR) unless specified. Results: In 190 individuals (age 50 (40-64) years, 55% female, time from symptom onset 98 (35-179) days), NT50 most highly correlated with anti-RBD IgG (Rho 0.81 p<0.001, Fig 1a) compared with other IgG classes (S1;Rho 0.8, S2;0.73, NC;0.72, all p<0.001). Median RBD titre was 246 (71-662) but trended lower over time, with a median of 319 (61-1012) IU/ml at 0-90 days, 244 (86-523) IU/ml at 90-180 days and 157 (80-364) IU/ml at >180 days post symptom onset respectively (p=0.08, Fig 1b). RBD IgG titres of 476 IU/ml corresponded to a NT50 of 1:1000. Overall, RBD ≥476 IU/ml predicted NT50 ≥1:1000 with a sensitivity of 77 (95% CI 65-87)% and specificity 89 (95% CI 82-93)%. This improved in an analysis restricted to convalescent samples (>30 days post symptom onset, n=148), with a sensitivity 88% (95% CI 74-96%) and specificity 90% (95%CI 82-95%) respectively. Conclusion: In convalescent plasma, RBD IgG titres ≥476IU/mL is sensitive and specific for predicting robust underlying neutralising capacity. Further research is required to validate these findings in other cohorts and confirm these thresholds in post-vaccinated individuals.
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Background: Coronavirus disease 2019 (COVID19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has varied clinical presentations from mild subclinical to severe disease with high mortality. Our aim was to determine whether examining immune-related gene expression early in infection could predict progression to severe disease. Methods: In subjects of the All Ireland Infectious Diseases Cohort study, we analysed expression of 579 genes with the NanoString nCounter Immunology panel in peripheral blood mononuclear cells in those with confirmed SARS-CoV-2 infection collected within 5 days of symptom onset and matched SARS-CoV-2 negative controls with respiratory infection. Subsequent maximum COVID19 disease severity was classified as mild or severe. Read counts were normalized using panel housekeeping genes. Expression changes in severity groups were estimated against control baseline. Results: Between April and July of 2020, we recruited 120 subjects, 62 with COVID19 and 58 controls, with average age 59 y.o. (IQR 34-88), 66% males and 69% Caucasian ethnicity. Maximal disease severity was used to separate COVID19 cases into mild (n=31) and severe (n=31). We identified 20 significantly deregulated genes between those with COVID19 and controls (;log2 fold;>0.5, p<0.05, Benjamin-Yekutieli p-adjustment). Function of 12 of these genes related to cytokine signaling, 9 upregulated genes to type I interferon signaling (MX1, IRF7, IFITM1, IFI35, STAT2, IRF4, PML, BST2, STAT1), while 7 downregulated genes mapped to innate immune function (IRF7, ICAM2, SERPING1, IFI16, BST2, FCER1A, PTK2). Expression in the severe group showed downregulation of FCER1A (innate immunity regulation), IL1B and TNF (inflammatory cytokines), and PTGS2 (inflammatory mediator) and greater upregulation of TNFSF4 (cytokine signaling) and PTK2 (innate immunity). Mild cases presented higher upregulation of IFIT2 (type I interferon signaling). Conclusion: Observed early downregulation of regulators and mediators of inflammation in those who developed severe COVID19, suggested dysregulation of inflammation. Specifically, IFIT2 upregulation in mild cases and FCER1A downregulation in severe cases, points to early differences in host responses centered on deregulation of the interferon and inflammation responses. Whether these patterns reflect delayed interferon involvement in pathways to control the infection and contribute to pathological inflammation and cytokine storms observed in severe COVID19 requires further research.
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The COVID-19 pandemic spurred the development of methodologies to assess risk to economic development plans. To increase local recovery efforts, the federal government provides funding for regional economic development. Funds are allocated based on immediate needs as well as growth potential. This work advances the risk register methodology to prioritize infrastructure initiatives - potential projects, policies, or other actions an organization may take - while considering the influence of exogenous scenarios on priorities given the impact of COVID-19. The risk register identifies performance criteria which measure performance - for example, an initiative incentivizing restaurants to increase outdoor seating improves a create new jobs criterion. Next, the register identifies disruptive events and groups these events into scenarios. There are now two sets of data: the initiatives considered for implementations, and a set of disruptive scenarios, including a baseline. The register evaluates the impact of each scenario on each initiative. For each scenario, the initiative with greatest impact on performance criteria is ranked first, and so on for the remaining scenarios. These rankings mathematically capture the influence of each scenario on the priority of each initiative. The risk register mathematically quantifies the disruptiveness of each scenario, allowing the comparison of different disruptive events. This information can help determine how to allocate resources to improve system resilience. The risk register methodology is applied to a socio-technical system of systems. This work advances methods outlined in the Systems Engineering Body of Knowledge, specifically the System of Systems knowledge area. © 2022 IEEE.
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There is urgent need to identify goods which may be diverted to an alternative mode of freight movement due to the disruptions to priorities and decisions of logistics entities by Covid-19, container shortages, labor shortages, etc. Here diversion refers to the shift of goods in the logistics network that are typically moved via one freight mode - such as rail, highway, or air - to another mode. There has been significant effort to model this behavior for purposes of infrastructure planning by both national and regional transportation agencies. In the United States this has culminated in a gold standard behavioral/agent-based model supported by the Federal Highway Administration (FHWA) and implemented by state transportation agencies. This model is well established and demonstrated to successfully predict the diversion of goods from one mode to another in response to changes in the freight network. However, this model is limited to consideration of the requirements state or national transportation agencies value. As a result, the model requires large teams, years of work, and millions of dollars in funding. This scale is not acceptable for modeling of transient events such as container shortages which would dissipate before model completion. This work advances a novel approach to model this behavior that is sensitive to the requirements of a diverse set of stakeholders and conditions. © 2022 IEEE.
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Persistent symptomatic COVID-19 is a multi-system condition that affects approximately 10% of those with acute COVID-19 infection. Affected patients often have complex care needs requiring holistic and multidisciplinary care approaches, the kind routinely provided in general practice. However, there is a lack of evidence of appropriate general practice interventions for the condition. A scoping review was conducted using Arksey and O'Malley's 2005 five-stage framework[1], with later recommendations by Levac et al.[2] to examine the literature and identify knowledge gaps in general practice management of persistent COVID-19. Nineteen papers were selected for review. The studies spanned numerous geographical locations, encompassing several study designs, and a range of populations and sample sizes. The included studies used various definitions for persistent symptomatic COVID-19. The literature was analysed qualitatively, and six major themes were identified. These themes were (i) GP uncertainty, (ii) Listening and empathy, (iii) Assessment and monitoring of symptoms, (iv) Coordinating access to appropriate services, (v) Facilitating provision of continual and integratedmulti-disciplinary care and (vi) Need to facilitate psychological support. Overall, the findings show that general practitioners play a key role in the management of persistent COVID-19, but that more clinical guidance on appropriate interventions is necessary to enhance care. There is a need for scientifically accepted definitions for persistent COVID-19 to ensure that patients can be recognized, assessed and managed appropriately. Patient and public involvement should guide policy makers when developing future care models. Meanwhile, future research should evaluate the implementation and effectiveness of proposed management strategies and interventions.
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Pegylated Interferon (PegIFN) is the recommended first-line cytoreductive therapy in patients aged <40 years with essential thrombocythaemia (ET) or polycythaemia vera (PV). However, its use in patients >60 years is often limited due to concerns about tolerability. In this study, we evaluate the efficacy and tolerability of PegIFN in patients >60 years at University College London Hospitals (UCLH). Using electronic medical records, we identified patients with ET, PV or myelofibrosis at UCLH who commenced treatment with PegIFN between 2010 and 2020 and were aged >60 years on starting therapy. Data were collected until April 2021 to allow a minimum of 1-year follow-up. Complete Haematological responses were defined as per standard European Leukaemia Net criteria. Adverse events (AE) were graded 1-5 according to Common Terminology Criteria for Adverse Events (CTCAE). Thrombosis risk was graded according to IPSET criteria for ET patients. Patients with PV were classed as high risk if they were aged >65 or had a previous history of thrombosis. Eighteen patients were included in the study. The median age was 75.1 years (range 63-91), 61% were female. Ten out of 18 (56%) had a diagnosis of ET, seven out of 18 (39%) of PV and 1/18 (6%) of post-ET myelofibrosis. Fifteen out of 18 (83%) were positive for JAK2 V617F, and two out of 18 (17%) were positive for CALR mutation. Ten out of 18 (56%) had significant cardiovascular co-morbidities at diagnosis. Five out of 18 (28%) had arterial or venous thromboembolic disease at diagnosis. Sixteen out of 18 (89%) were high-risk for thromboembolic events at diagnosis. Seventeen (94%) patients had PegIFN as a second-or thirdline agent. Of these, 15 out of 17 had received hydroxycarbamide (HU) as first-line therapy;two out of 17 had interferon alpha. PegIFN was started at a median age of 70 years (range 50-86) and continued for 5.7 years (range 2-13). Twelve out of 18 (67%) patients achieved complete remission (CR) on PegIFN monotherapy;1 out of 18 (6%) achieved CR on PegIFN and HU combination therapy, and the remaining 5 out of 18 (28%) achieved a partial remission (PR). The median time to CR was 5 months (range 1-40 months). Ten out of 18 (56%) had grade 1-2 AEs including skin rashes, cytopenia and fatigue. Three out of 18 (17%) developed a major thromboembolic event while on treatment (brachial artery embolism, transient ischaemic attack and a non-ST elevation myocardial infarction). Of these, two out of three failed to achieve a CR on PegIFN and required ongoing venesection. The third had suboptimal response due to dose escalation limited by grade 3 neutropenia. Thirteen patients (72%) remained on pegIFN at the end of the study period. Of those who discontinued, three out of five stopped due to cytopenias, one out of five died during the study period of Covid-19 infection and one out of five transformed to myelodysplastic syndrome. In this study, we present a group of patients who were at high risk for thrombosis due to their age and cardiovascular risk factors. The majority of AEs documented were grade 1-2, with only three out of 18 (17%) patients discontinuing due to AEs. The rate of CR 72% similar to that quoted in imminent studies including MPN-RC (Knudsen et al, 2018) and DALIAH trials (Mascarenhas et al, 2018), which recruited larger numbers of youngers ET and PV patients on PegIFN. Over 20% of MPN patients develop resistance or intolerance to HU (Sever et al, 2014);therefore, there is a need for alternative cytoreductive agents. Our study demonstrates PegIFN to be effective and well-tolerated for use in patients >60 years and is an excellent cytoreductive option in this cohort.
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Aims: To describe the characteristics, symptoms and outcomes for patients with COVID-19 referred to a hospital-based specialist palliative care service and to describe communication and visiting practices. Methods: A descriptive cross-sectional retrospective study, which is a part of the ANTICIPATE study project. Results: 50 patients were referred;49 included in analysis. 38 patients died. 27 patients were male;median age was 81 years. On referral, median Charlson Comorbidity Index was 6;median Australia-modified Karnofsky Performance Status score was 20%. Median number of days from referral to death was 2. Common baseline symptoms (n) were dyspnoea (35), agitation (23), and pain (13). Opioids (100%), benzodiazepines (97.1%) and neuroleptics (61.8%) were most commonly used medications to achieve symptom control. 13/19 patients with serial data had a decrease in Palliative Care Problem Severity Score. 26 patients received a family visit before death;8 had virtual forms of contact. 9 patients had family present at time of death. Conclusion: The short interval from referral to Specialist Palliative Care and death indicates the need for prompt service response. Data on visiting highlights challenges of providing psychosocial support.
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It was suggested that all SARS-CoV2 infections lead to development of specific IgG antibodies that remain detectable in time. Targeted Immune-Modulating Therapies (TIMT) for treatment of Immune Mediated Inflammatory diseases (IMID) could interfere with humoral immune response against COVID-19. To investigate the seroprevalence of SARS-CoV2 IgG in relation to previous exposure to COVID-19 and ongoing IMID treatment a cross-disciplinary, prospective observational cohort was set up at two Belgian university hospitals. Between 17/12/2020 and 28/02/2021, patients with IMIDs of the skin (psoriasis (PsO), hidradenitis suppurativa (HS), atopic dermatitis (AD)), gut or joints were asked to participate. Patients under conventional systemic treatment or TIMT were included. An electronic survey (REDCap®) and blood samples were obtained (SARS-CoV-2IgG Abbott–Architect kit®). Statistical analyses were performed with SPSS26. 2166 IMID patients consented to take part. 1913 completed the survey: 218 dermatology patients (77% PsO, 12% HS, 11% AD), 415 rheumatology and 1217 IBD patients. 372 patients (19.5%) reported having experienced symptoms suggestive of COVID-19: fatigue (61.3%) and headache (48.1%) were most frequent. 96 patients (5.04%) had a positive SARS-CoV2 PCR test on nasal or throat swab: in 45.8% anti-SARS-CoV2 IgG seroconversion was confirmed. There was no significant difference in seroconversion rate between the 2 treatment groups (P=0.192). Of the seroconverted group, 75.0% were treated with TIMT. Prevalence of COVID-19 symptoms and number of confirmed COVID-19 cases remain low in this IMID cohort, regardless of treatment modality. There was no significant difference in SARS- CoV2 IgG seroconversion rate between TIMT and conventional systemic treatment in patients with positive PCR.
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Learning Objectives: 1. Provide a virtual learning experience showcasing EM for pre-clinical URM medical students with no prior EM exposure. 2. Guide students through a scholarly presentation exploring basic study design in EM specific topics. 3. Provide individualized mentorship with URM EM residents and faculty. : The EM Department at NYU Langone hosts a monthlong fully funded summer fellowship for rising second year underrepresented in medicine (URM) students from medical schools across the country. During the COVID-19 pandemic, our fellowship transitioned to remote learning to limit disease transmission. Learning objectives typically taught via in-person workshops and clinical shifts were presented in virtual presentations and interactive demonstrations. Equipment such as suture kits, splinting supplies, and wilderness medicine gear was mailed to students prior to the start date. Google classroom, Zoom, and Webex were used to facilitate the online classroom. 15 faculty and 8 residents participated through workshops, didactics, panel discussions, journal clubs, 1:1 mentoring, and Q&A sessions. Each student worked on a scholarly project throughout with their resident and faculty mentor and then presented it on the last day. The focus of the scholarly project was changed from a clinical focus to a social medicine issue in the students' local communities. We hosted 4 visiting URM students and 2 NYU students. The curriculum was rated from 0 to 10, with resident didactics (7) rated 8.17 (SD 1.91), faculty lectures (15) rated 8.05 (SD 2.20), resident simulation workshops (2) rated 8.75 (SD 1.60), and resident procedural workshops (2) rated 8.58 (SD 1.96). Every participant reported that they are more likely to pursue EM after the fellowship compared to before. This successful transition to a virtual classroom is a viable option to consider for programs seeking to continue education while reducing risk of disease transmission.
ABSTRACT
Background: Immunomodulators (IMM) and Targeted Immune-Modulating Therapies (TIMT) such as anti-TNF, anti-interleukins and Janus Kinase inhibitors, for treatment of Immune Mediated Inflammatory diseases (IMID) could theoretically interfere with the cytokine storm and humoral immune response against COVID19 infection and vaccination. We investigate seroprevalence and evolution of SARS-CoV2 antibodies in relation to previous vaccination and/or exposure to COVID19 and ongoing IMID-treatment in a Belgian, reallife population of IMID patients. Methods: A cross-disciplinary, prospective, observational cohort study was set up at two university hospitals. All patients with IMIDs of the gut (Crohn's disease, ulcerative colitis), joints (rheumatoid, psoriatic or spondyloarthritis) and skin (psoriasis, hidradenitis suppurativa, atopic dermatitis) visiting the respective clinics were asked to participate. Patients had to fill out an electronic survey (REDCap®, based on WHO-ISARIC) and blood samples were drawn for serology testing (anti-Spike(S) and antiviral Nucleocapsid(N) protein antibody IgG, Abbott). Results at baseline, prior to the national vaccination program and at 6 months follow-up are presented. R version 4.0.2 was used for statistical analyses. Results: At baseline 2165 IMID patients consented to take part. In 3.2% SARS-CoV2 anti-N seroconversion was confirmed. Of the anti-N seroconverted patients 72.9% reported a positive PCR test prior to inclusion. At 6-months follow-up, data of 1853 IMID patients was collected. Of these, 81.7% were fully and 14.4% partially vaccinated. Seroconversion for anti-N antibodies was confirmed in 2.5% of all participants and seroconversion for anti-S antibodies in 90.8%. In 5.1% (61/1483) of fully vaccinated IMID patients no seroconversion in anti-N nor anti-S antibodies was found. Chi Square analyses show, at 6-months follow-up, no significant association between anti-S seroconversion rate and treatment with systemic steroids (RiskRatio 1.22, 95%CI 0.38-3.9, P=0.99), TIMT (RiskRatio 0.57, 95% CI 0.3-1.1, P=0.12), IMM (RiskRatio 1.65, 95% CI 0.85- 3.19, P=0.19) or combination treatment IMM/TIMT (RiskRatio 1.60, 95% CI 0.75-3.4, P=0.32). Appearance of COVID19 symptoms followed the epidemiological curve in Belgium (Fig1). Conclusion: In this real-life IMID cohort, the number of COVID19 cases confirmed by PCR prior to vaccination was low. Seroconversion rate for anti-N antibodies was lower at 6-months follow-up, suggesting decrease in antibody titre over time. Full COVID19 vaccination led to a high anti-S antibody seroconversion rate. Nonetheless, 5.1% of fully vaccinated patients showed no antibody seroconversion. So far, no significant association between anti-S antibody seroconversion and IMID treatment was noted.