Olfactory Performance in Post Mild-to-Moderate Acute Covid-19 across 2 Years

Background: Previous longitudinal studies (n=6) of objective olfaction performance post-acute COVID-19 have a maximum follow-up of 6-month and do not often test biomarkers. Although olfactory dysfunction appears to improve within two months of symptom onset, 4/6 longitudinal studies show persistent olfactory impairment. Method(s): PCR-confirmed COVID-19 patients in the prospective ADAPT cohort (Sydney, Australia) were assessed across 18 acute symptoms and hospitalization status: 40% mild, 50% moderate, 10% severe/hospitalised - none deceased). Blood samples were taken 2 (N=179), 4 (N=148) and 12-month (N=118) post-diagnosis. The NIH Odor Identification Test (OIT) and the Cogstate brief cognitive battery were performed. 58 also had an olfaction test at 24-month. The OIT raw data were transformed into demographically-corrected T-scores. OIT's attrition was completely random and only initial age (40+/-15 versus 47+/-15) differed between patients lost to follow-up and those in the study at 24-month. We tested peripheral neurobiomarkers (NFL, GFAP, S100B, GM-CSF) and immune markers (Interleukin-IL panel: 1-beta, 1Ralpha, 4, 5, 6, 8, 10, 12p40, 12p70, 13, and MCP-1, TNF-alpha and INF-gamma), analyzed as Log transformed and elevated/normal range using published references. Our previous analyses had shown no relationship with the kynurenine pathway, but an association of impaired olfaction and impaired cognition at 2-month only. Linear mixed effect regressions with time effect (months) tested olfaction trajectories (random subject effect) and their association with the biomarkers (main and time interaction). Result(s): At 2 months post-diagnosis 30% had impaired olfaction and those who had acute severe disease were more likely to be impaired (54% versus 26%, p=.009). 21%, 31% and 37% had impaired olfaction at 4, 12 and 24-months. Olfactory performance declined over time (p< .0001), which was dependent on the initial performance (Fig 1). Neurobiomarkers were within the normal range. IFN-gamma, IL-1Ralpha, IL-13 and TNF-alpha increased across time, p< .03-p< .0005. TNF-alpha and IFN-gamma showed a time covariance with poorer olfaction performance. Conclusion(s): Post-acute mild to moderate COVID-19 is associated with a declining olfactory performance up to 2-yr post-diagnosis, especially when initially impaired with the provisio of attrition although random. Olfactory performance decline may be mediated by upregulated immune parameters which are distinct from those driving cognitive changes. (Figure Presented).

Modern a COVID-19 Vaccine-Induced Immune Thrombosis of Central Retinal Artery-Report of a Case

Objective: To report a rarely isolated central retinal artery occlusion (CRAO) following Coronavirus disease 2019 (COVID-19) Vaccine Moderna (mRNA-1273). Background: COVID-19 caused by severe acute respiratory syndrome coronavirus was firstly reported in Dec 2019 and became pandemic as of Mar 2020. Fortunately, novel rapidly developed COVID-19 vaccines are capable of lessening the pandemic effectively. As billions of people vaccinated, however, COVID-19 vaccine-induced thrombosis (VIT) are gradually emerging. Design/Methods: A previously healthy 70-year-old man presented with acute painless visual loss of the right eye five days after the first dose of Moderna vaccine. On examination of the right eye, visual acuity (VA) was counting finger at 15 cm. Fundoscopy revealed a diffuse whitened retina with cherry-red spot. Optical coherence tomography (OCT) showed hyperreflectivity. Screening tests for platelet and D-Dimer levels were unremarkable. CRAO was treated with clopidogrel and hyperbaric oxygen therapy. The serum level of anti-platelet factor-4 (PF4) antibody was 73.34 ng/ml (ref, 0-49.99 ng/ml).Two months later, VA was counting finger at 10 cm3 and OCT revealed hyperreflectivity and mild inner retina atrophy Results: COVID-19 vaccine-induced thrombosis and thrombocytopenia (VITT) based on the victims receiving AstraZeneca and Johnson & Johnson vaccines is through autoimmune antibody against PF4. VITT is typically manifested within 6-24 days post-vaccination;thrombotic sites are in the cerebral sinus, portal vein, splanchnic vein, and pulmonary emboli;as well as thrombocytopenia and increased level of D-Dimer. Our patient had isolated CRAO five days post-Moderna vaccination but normal platelet count and D-Dimer level. Moreover, VIT with isolated CRAO was not published on PubMed. Conclusions: VIT could occur in the unusual site such as CRAO in our case. Normal platelet and D-Dimer levels might not be sensitive tools to exclude VIT. Suspected patient with thrombotic event after COVID-19 vaccines should have anti-PF4 antibody test to assure an effective treatment.

QUINOLINIC ACID IS A BIOMARKER of COVID-19-ASSOCIATED COGNITIVE IMPAIRMENT

Background: COVID-19 infection-associated cognitive and olfaction impairments have an unclear pathogenesis, possibly related to systemic disease severity, hypoxia, or illness-associated anxiety and depression. A biomarker for these neurocognitive changes is lacking. The kynurenine pathway (KP) is an interferon stimulated myeloid cell mediated tryptophan degradation pathway important in immune tolerance, neurotoxicity and vascular injury, that is dysregulated in COVID-19. We hypothesized that neurocognitive impairments were associated with an activated KP. Methods: The current analysis includes COVID-19 patients as part of the ADAPT study, a prospective cohort (St Vincent's Hospital Sydney, Australia). Disease severity was assessed with 18 acute symptoms and hospitalization status. Blood samples were taken 2 months (N=136) and 4 months (N=121) post diagnosis along with cognitive (Cogstate Computerized Battery, CBB;NIH toolbox Odor Identification Test, OIT) and mental health screenings (DMI-10;IESR, SPHERE-34 Psychological subscale grouped into a composite score). KP metabolites (PIC, QUIN, 3HK, 3HAA, AA, KYN, TRP, log for analyses except for TRP) were measured by GC-MS and uHPLC. The CBB and OIT data were demographically-corrected. CBB follow-up data was also corrected for practice effect. Linear mixed effect regression models with time effect (days post diagnosis) tested whether cognition, and olfaction were associated the KP (main and time interaction);while correcting for disease severity, mental health and comorbidities. Results: 136 patients: mean age=46±15;40% females;90% English speaking background;disease severity: 40% mild, 50% moderate, 10% severe/hospitalised;34% treated comorbidities. At 2 months post diagnosis, 16% had cognitive impairment, and 25% had impaired olfaction. Cognitive impairment was more common in those with anosmia (p=.05). At 4 months, 23% had cognition impairment and 20% had impaired olfaction. QUIN (p=.001), 3HAA (p<.0001) increased over the study period, while TRP decreased (p=.02). QUIN level associated with poorer cognitive scores (p=.0007;QUIN (nM) between 800-1000 was most predictive). There was no time∗QUIN interaction. QUIN association to cognition persisted when severe cases were excluded (p<.005). Conclusion: COVID-19 is associated with KP activation, and the latter with cognitive impairment. QUIN was the only biomarker associated with cognitive impairment, and may be useful in monitoring and elucidating COVID-19 neuropathogenesis and treatment.

Searching for Service and Accessibility Excellence in Paroxysmal Nocturnal Hemoglobinuria in Canada: The Epic Program

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease affecting 1-10 per million per year, characterized by uncontrolled complement-mediated intravascular hemolysis, thrombosis, and marrow failure. PNH manifests in a wide variety of symptoms such as fatigue, dyspnea, chest pain, abdominal pain, and hemoglobinuria. Due to its nonspecific presentation, patients may experience a delay in accurate diagnosis of this rare disease, which has been shown to have a significant impact on quality of life (QoL) and survival. At any point in the patient's journey, they may experience delays or poor accessibility to care. Key challenges in PNH remain its initial identification, diagnosis, and subsequent timely treatment. Methods: The Canadian PNH Network (CPNHN) use the “CATCH criteria” to suspect diagnosis of PNH: Cytopenias, Aplastic anemia/myelodysplasia, Thrombosis, Coombs‘-negative hemolysis, and Hemoglobinuria. This screening tool has not been formally validated, however it was hypothesized to be useful for real-world practitioners. In this study, we aimed to: (1) identify opportunities and gaps during the journey of a patient with suspected or confirmed PNH, referred to a CPNHN center (Pilot sites: University Health Network (UHN) & Sunnybrook Health Sciences Centre (SHSC));(2) characterize time to diagnosis and treatment initiation, specifically considering CATCH criteria;and (3) assess the presentations with the highest frequency of being referred to a CPNHN center to create a process map. Results: A total of 19 participants were identified at UHN, 17 charts were reviewed, and 15 patients were available for 30-minute individual interviews. The timeline was based on the participants’ initial presentation to start of targeted treatment (i.e., eculizumab). Baseline demographic data are presented in Table 1. Mean age at diagnosis was 46.1 years (standard deviation [SD] 16.7), with varied symptoms at presentation (Figure 1). Median number of healthcare providers seen prior to diagnosis and/or referral was 6 (interquartile range [IQR] 4-10;Figure 2), and time from symptom onset to referral was 17 months (IQR 6-67). The most common CATCH criteria at presentation were hemoglobinuria, Coombs'-negative hemolysis, and cytopenias (i.e., anemia and thrombocytopenia) (Table 2). Flow cytometry revealed large granulocyte (85.9% ± 16.9), monocyte (84.7% ± 17.4), and type III RBC (20.8% ± 18.5) populations. From the interviews, we noted that individual participants had diverse experiences and journeys with PNH. Reflecting on the COVID-19 pandemic, participants reported no change in quality of care they had received, and some endorsed the convenience of virtual consultation without being required to travel long distances for in-person visits. Several suggestions included: improving community physician awareness and education on PNH, assistance with finances (transportation/parking), and need for ongoing patient education on available medications and clinical trials. Discussion and Conclusion: PNH is a rare disease that can manifest in many different, non-specific ways, contributing to delays in diagnosis and treatment initiation. We have characterized the patient journeys of a cohort of patients followed at our centers, and have identified gaps and potential areas for improvement. The variability and delay in assessment for PNH may be attributed to the diverse backgrounds of the participants, first presentation abroad, year of symptom presentation, and availability of high-sensitivity flow cytometry, which is the diagnostic gold standard. In addition to characterizing the initial presentations and barriers to diagnosis and treatment, we also evaluated humanistic factors such as QoL. As PNH is rare, the study was limited by the small sample size and some incomplete records, as some patients were diagnosed and managed elsewhere initially. We plan to expand our work across Canada, which will increase our cohort size and better allow an assessment of the impact of geographical differences on a cess to care. Following this, we plan to provide recommendations for diagnostic and treatment benchmarks to colleagues across the country, introduce the CATCH criteria, and subsequently evaluate the impact of these knowledge translation strategies with comparison to our initial cohort. [Formula presented] Disclosures: Chow: Alexion: Other: Site investigator for clinical trial. Patriquin: Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Speakers Bureau;Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Biocryst: Honoraria;Sanofi: Honoraria.

Writing memory: Three visual diaries related to 'pharmacy'

Diaries offer a private space to play tic-tac-toe with intellectual, artistic and personal complexities, practice wielding or calling upon language, confess amorous feelings, sharpen the switchblades of resentment, and so on. Accompanied by this general outline of what a diary is for, the diaries made by contemporary Chinese artists related to COVID-19 are neither written for themselves or for their future readers. It should belong to the third category as a public diary for living contemporary people. It challenges the concept of 'author' both in literal and art discourse and might make the identity of the diary more and more obscure. Are these diaries still private art? Or before it was created, has it already become public art? This article will focus on visual diaries made by three contemporary Chinese artists, and study how the artists 'write' their own 'memory'.

The preliminary data of vaccine hesitancy in high-risk geriatric population

Background: Vaccines to prevent SARS-CoV-2 infection are deemed one of the most promising measures to control the devastating pandemic that has disrupted the United States and many countries worldwide. New York city started distributing vaccines to the geriatric population aged 75 or older on January 11th, 2021. ALIGN (Acute Life Interventions, Goals, and Needs) program at the Mount Sinai Hospital is a specially designed outpatient service to offer intensive ambulatory care to the most vulnerable older patients with complex medical and psychosocial needs. Though two vaccines are already approved by the FDA and available to American population, previous surveys from Pew Research Center have shown that around 40% of population probably or definitely would not get the vaccine. Given that persons most at risk for complications of COVID-19 include the older population, and those with heart, lung, and diabetic diseases, it is critical to overcome the vaccine hesitancy especially in the high-risk geriatric population. As the vaccine has only just become available to the older population, the data specific for this population is lacking. Methods: All 68 patients followed by our outpatient program were eligible for the vaccine as part of Phase 1b and 1c. Eligible patients were contacted by phone and vaccine risks, benefits, and patientspecific recommendations were discussed with the patient or patient's healthcare proxy. The patients were also asked if they were willing to be vaccinated. If they answered 'yes', they proceeded with making appointments. If the answer was no, then the clinical team further probed for reasons and barriers for declining the vaccine. Qualitative data was categorized into themes and subgroups. Demographic data was collected by chart review. Results: Results including the proportion of older patients willing to be vaccinated, the reasons for vaccine hesitancy, and clinical team member debrief will be forthcoming. Conclusions: We conducted a brief qualitative report characterizing vaccine perceptions and hesitancy in a high-risk older population. This preliminary data informs healthcare providers of potential health literacy, cultural and language, and other potential barriers in order to help further understand how to optimize SARSCoV-2 vaccine acceptance and delivery.

In-basket scrubbing to improve geriatrician well-being

Background Our 2019 survey showed 50% of geriatricians had burnout by Maslach Burnout Inventory (MBI), 79% had electronic medical record (EMR) frustration, 54% spent >60 minutes on the EMR outside of workday and 32% spent >60 minutes/day on clerical work. The COVID-19 pandemic added to the strain. In September 2020, 69% of our geriatricians reported in-basket management makes them feel “most overwhelmed.” Prior research shows the benefit of nonphysician staff reviewers for in-basket messages. We will improve geriatrician well-being and productivity with a new Patient Coordinator In-basket Scrubber Intervention. Methods We will target 21 geriatricians providing primary care to older adults at three outpatient sites. We will recruit and train two Patient Coordinators (PCs) who will lead a novel In-basket Scrubber intervention. Initially, the PCs will be the first contact to scrub (screen and send to correct team member) all in-basket messages from the call center. They will identify inefficient communication patterns, code messages by “team member” and “domain” and determine the destination and/or outcome of the messages. The PCs will train administrative assistants (AAs) to assess, complete and/or appropriately redirect providers' in-basket messages to team nurses, social workers or the physician. We will also target our telehealth workflow to improve scheduling and appointment confirmation, reduce no-shows and convert canceled visits to tele-visits, thereby increasing reimbursable visits. Results Results forthcoming. At months 0, 6, 12, and 18, we will assess physician EMR burden, well-being, and productivity. Measures include: EMR burden (Number of Inbox Inputs per workday, Time in Inbox per workday, Work after Work 7pm to 7am);Well-being (Subjective Inbox Burden, Maslach Burnout Inventory);Productivity (In-person visits Televisits, Medicare Annual Wellness Visits, advance care planning bills, chronic care management bills, work relative value units). We expect the intervention to reduce EMR burden and improve well-being and productivity. We also expect new revenue to offset costs. By reducing clerical burden and optimizing billable time for care coordination, we expect to double our Chronic Care Management billing (estimated $75,000/year). Conclusions We will improve geriatrician well-being through a new In-basket Scrubber Intervention.

Creation of a diversity, equity, and inclusion initiative to address systemic racism

Background: Catalyzed by the horrific death of George Floyd, a Black man, significant concrete efforts to engage workplaces in Diversity, Equity, & Inclusion (DEI) initiatives has gained prominence and administrative backing among workplaces in the United States. A diverse academic geriatrics & palliative medicine department in New York City began meeting weekly in Town Hall sessions to debrief & discuss workplace, local, & national concerns. Discussions focused on COVID19, the Black Lives Matter movement, structural racism, & patient care inequities. These events ignited greater DEI initiatives to meet departmental needs. This report serves to highlight key program components & lessons learned in launching a structured DEI initiative in the academic medicine setting. Methods: First, a new DEI core & department administration met 2-4 times/month to plan & review DEI program activities, vision, & mission. Confidential roundtable discussions about DEI issues & 1:1 interviews were conducted to assess needs. A monthly Humanities, Arts, & Books (HAB) Initiative provided a safe space for discussion & l earning. The HAB platform supported a longitudinal curriculum emphasizing (1) group discussion & self-reflection on DEI topics, (2) knowledge dissemination including a “Learning Pathway” series, & (3) skill-based workshops. With each event, we collected anonymous feedback via survey. Comments were systematically recorded & engagement evaluation was conducted in order to iteratively shape future sessions. Departmental administration was engaged to track DEI-focused measures of recruitment, career advancement, & retention. Finally, we centralized DEI activities on a departmental website, including an anonymous online feedback box. Results: Quantitative & qualitative assessment of DEI initiatives are forthcoming. Metrics include DEI & professional development surveys, departmental demographic & diversity measures, increase in DEI-related projects and grants, & individual participation DEI programs. Conclusions: Creating a strong and sustainable DEI initiative within an academic medical setting requires a passionate and diverse core to centralize efforts, deliberate backing by administration, & thoughtful dissemination of sensitive content in the midst of a highly charged social justice landscape.