Troubled times: Canadian social workers' early adversities, mental health, and resilience during the COVID-19 pandemic

Canadian social workers were surveyed about early adversities, mental health, and resilience. Bivariate analysis (n = 236) was conducted to understand relationships between predictor and outcome variables;and logistic regression analyses were conducted for depression, post-traumatic stress disorder, anxiety, and resilience. The impact of pandemic-related factors was also investigated. The results indicate that social workers are experiencing concerning levels of mental health issues, with significantly lower levels of resilience in younger social workers. A trauma and resilience informed approach to workplace policies and practices is urgently required to support social workers' mental health needs.

Seasonal Increase in Syphilis Positive Testing Rate in Whole Blood Donors 2018-2021

Background/Case Studies: On December 17th 2021 the U.S Food and Drug Administration published a letter to clinical laboratory staff and health care providers detailing a risk of false Rapid Plasma Reagin (RPR) when using the Bio-Rad Laboratories BioPlex 2200 Syphilis Total & RPR kit in people who had received a COVID-19 vaccination. Specifically, this notice stated that Treponema pallidum particle agglutination (TP-PA) assays did not appear to be impacted by this issue. At our institution it has been observed that since 2018, the positivity rate of syphilis screening with negative confirmatory testing has been dramatically increased from previous years. Curiously a striking number of these positives occurred at the end of the year, mainly October through December. Study Design/Methods: All whole blood (WB) donations from 2011-2021 which demonstrated positive syphilis screening with negative confirmatory testing were evaluated. Screening for syphilis was performed using the Beckman Coulter PK TP Microhemagglutination assay with confirmatory testing using CAPTIA Syphilis (T. pallidum)-G. Results/Findings: There were 77 whole blood donations from 59 unique donors screened positive for syphilis with negative confirmatory testing from 2011-2021 (summarized in table 1). A dramatic increase in the unconfirmed syphilis positivity rate was observed in 2018-2021 (mean: 0.439%) compared to 2011-2017 (mean: 0.024%, unpaired t-test p-value: 0.0010), representing an 18-fold increase in positive screens. Of these 77 donations, 8 donors contributed 26 units (median: 3, range: 2-5) between 2018-2021. Three of these 8 donors made several (6, 31, and 85) WB donations with negative syphilis screening prior to becoming positive. The 5 remaining donors switched back and forth between negative and positive over the course their donation history. Conclusion(s): There has been a statistically significant increase in unconfirmed syphilis positivity rate among whole blood donors at our institute since 2018 when compared to the 7 years prior. Additionally, the positivity rate doubled from 2020 to 2021. No changes were made to the testing assay used during this time period that could explain these results. There appears to be an autumnal peak in unconfirmed positives suggesting a possible environmental trigger such as viral infection or influenza/COVID-19 (for the 2021 increase) vaccination. Further investigation would be needed to confirm such a hypothesis. (Table Presented).

Assessment of curbside anticoagulation pharmacy visits on clinical outcomes and patient satisfaction

Introduction During the coronavirus disease 2019 (COVID-19) pandemic, curbside international normalized ratio (INR) checks were implemented to monitor patients on warfarin therapy. Because of the lack of available data, clinical outcomes and patient satisfaction were assessed to determine if the implementation of curbside visits could be considered as an alternative to the standard of care. Objectives The objectives were to assess clinical outcomes, safety, and patient satisfaction in a patient cohort whose anticoagulation was managed inside the clinic in 2019 compared with the same patients managed in the curbside setting in 2020. Methods In this retrospective study, INR time in therapeutic range (TTR) was used as a marker for clinical appropriateness of anticoagulation therapy. Data were also prospectively collected in the form of patient satisfaction surveys. Adverse events and hospitalizations were assessed to ensure patient safety was not omitted. Results The median TTR in 2019 was significantly higher than in 2020, 95.7% (interquartile range [IQR] 33.3%) vs 84.3% (IQR 45.2%) (z = -3.99, P < .001). Clinically, the mean TTR remained higher in 2019 than in 2020 (81.3% vs 74.7%). Less patients experienced bleeding events in 2020, and there was an average of 1 less visit per patient in 2020 compared with 2019. Surveys indicated that more patients would like their visits to occur inside the clinic if there were no concerns for a pandemic. Conclusion Anticoagulation management assessed by TTR was significantly lower in the 2020 time frame compared with 2019;however, the average TTR in both time frames was above the clinically accepted threshold of adequate anticoagulation control. Patients demonstrated favor toward in-person visits unless there were concerns for a pandemic. If needed, curbside visits could be considered in the future at this site;however, more studies would need to be done to assess the impact of curbside visits at other institutions.

COVID-19 Antibody Detection and Assay Performance Using Red Cell Agglutination

Background. Serologic assays detecting antibodies against the SARS-CoV-2 spike or nucleocapsid proteins have been developed to advance our understanding of the prognosis and clinical course of the COVID-19 disease. We recently developed a red cell agglutination-based assay to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. This assay uses peptide fragments of the SARS-CoV-2 spike protein to label red cells (C19-kodecytes). We performed a clinical evaluation of this C19-kodecyte assay in COVID-19 convalescent plasma (CCP) donors previously assessed with 2 commercial immunoassays and a virus neutralizing assay. Methods. Red cells were coated with peptide fragments of the SARS-CoV-2 spike protein. We tested plasma samples from 140 CCP donors. The results were compared with those of a virus neutralizing assay and 2 commercial chemiluminescent antibody tests: anti-SARS-CoV-2 Total (IgG, IgM and IgA) assay and anti-SARS-CoV-2 IgG assay (Ortho). Inter-rater agreement between the different assays was measured using Cohen's kappa. Specificity was tested with 150 plasma samples, collected in 2008, more than a decade before the COVID-19 outbreak and with 125 plasma samples, collected in 2020 from consecutive healthy volunteer donors, who tested negative for the Ortho Total assay. Testing was performed using the column agglutination technique commonly employed for blood typing. Results. The area under the ROC curve (AUC) for the C19-kodecyte assay reached 0.95 (95% CI: 0.93 - 0.97) with sensitivity of 92.8% (95% CI: 86.9% - 96.3%) and specificity of 96.3% (95% CI: 93.2% - 98.1%). In almost all of the 40 CCP donors with longitudinal data, the antibody concentration decreased during the follow-up, which ranged from 7 to 44 weeks. In the 140 CCP donors, we compared the C19-kodecyte score to the antibody concentrations from the 2 FDA authorized assays (Ortho Total and Ortho IgG) and the titer in the neutralizing assay. There was a positive relationship between the results of all 4 assays. The Spearman's correlation of our assay was 0.20 with the neutralizing assay (0.49 with IgG, and 0.41 with Total assays). Conclusions. Sensitivity and specificity of the C19-kodecyte assay were within the minimum performance range required by the FDA for EUA authorization of serology tests. The limited correlation in assay reaction strengths suggested that the assays may be influenced by different antibody specificities. Unlike the other 84 FDA authorized serologic tests for SARS-CoV-2, this C19-kodecyte assay is a simple and rapid test that can be easily established in any blood typing laboratory worldwide using its routine setup for column agglutination or tube technique. The technique could vastly improve assay capacity, particularly in resource limited hospital blood banks. Disclosures: Bovin: Kode Biotech: Current Employment, Current holder of stock options in a privately-held company. Henry: Kode Biotech: Current Employment, Current holder of stock options in a privately-held company.

Longitudinal Transcriptional Analysis of Peripheral Blood Leukocytes in COVID Convalescent Donors

Introduction Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) can induce a strong host immune response. Several groups have investigated the course of antibody responses in patients recovering from SARS-CoV-2 infections but little is known about the recovery of cellular immunity. This study investigated the cellular immune response in people who had recovered from SARS-CoV2 infection. Methods 162 coronavirus disease 2019 (COVID-19) convalescent plasma donors (CCD) and 40 healthy donor (HD) controls were enrolled prospectively in an IRB-approved protocol (Clinical Trials Number: NCT04360278) and provided written informed consent to participate in the study. Using the nCounter platform and host response panel with 785 genes across more than 50 pathways, we compared transcriptomic profiles on RNA samples obtained from the peripheral blood leukocytes of these 162 CCD and 40 HD. Additionally, in 69 of the 162 CCD samples, we evaluated transcriptomic trends at more than one-time point during the convalescent period. Results Age, sex, ethnicity, and body mass index distributions were similar among the CCD and HD. With respect to baseline complete blood counts, hemoglobin, platelets, and absolute basophil and eosinophil counts, all were similar among CCD and HD (Table 1). However, despite sample collections occurring several days after convalescence, mean counts for absolute neutrophil counts, absolute monocyte counts, and absolute lymphocyte counts were significantly higher among CCD compared to HD. 30-90 days after diagnosis, 19 of 773 genes differed (FDR < 0.05) between the average CCD and HD samples. Up-regulated genes included MAFB, CTLA4, PTGS2, and the chemokine signaling genes CXCR4, CXCL5, CXCL2 and CCR4. Down-regulated genes included PTGER2, CASP8, and the interleukins IL36A, IL31, IL20 and IL21 (Figure 1 a,b). Differential gene expression persisted for months. At 90-120 days, 13 genes were differentially regulated, including again MAFB CXCR4, PTGS2, CXCL2 and PTGER2, plus SMAD4. At 120-150 days post-diagnosis, 58 genes were differentially expressed (FDR < 0.05) compared to HD. Pathways with up-regulated genes included Treg differentiation, type III interferon signaling and chemokine signaling. 150-360 days post-diagnosis, 4 genes remained up-regulated on average (FDR < 0.05): PTGS2, PIK3CR, CXCL1 and SMAD4 (Figure 1 c,d). Individual patients varied considerably from the mean trend. Scoring samples by their similarity to the gene expression profile of the mean HD sample, 21 CCD samples from 20 unique patients (12%) were identified as highly perturbed from HD. 84% of these highly perturbed samples were collected > 90 days post-diagnosis. Of these 21 samples, 6 were distinguished by > 2-fold up-regulation of a cluster of interleukin and type-1 interferon genes (Figure 2). Conclusions Overall, our study identified important gene expression trends in CCD compared to HD in the post-acute period. The changes varied with time and among donors. As the expression of T-cell inhibitory molecule CTLA4 fell, the number of differentially expressed increased with the most marked changes occurring 120 to 150 days post-diagnosis in genes in chemokine signaling, type III interferon signaling and Treg pathways. Persistent alterations in inflammatory pathways and T-cell activation/exhaustion markers for months after active infection may help shed light on the pathophysiology of a prolonged post-viral syndrome observed in individuals following recovery from COVID-19 infection. Our data may serve as the basis for risk modification strategies in the period of active infection. Future studies may inform the ability to identify druggable targets involving these pathways to mitigate the long-term effects of COVID-19 infection. [Formula presented] Disclosures: Danaher: NanoString Technologies: Current Employment, Current holder of individual stocks in a privately-held company.

Re-thinking Indigenous postgraduate whanaungatanga

The COVID-19 pandemic and resulting lockdowns in Aotearoa New Zealand have been a source of change, of uncertainty and of anxiety. The ways in which we engage with each other as Indigenous people have had to change drastically and suddenly;our ways of being, of sharing space, of being present, have all had to be adjusted. For Indigenous postgraduate students, COVID-19 and lockdowns have meant a re-shaping and re-thinking of how we come together as a community that supports each other within Westernised institutions and along our academic and research journeys. This situation report delves into some of the Indigenous postgraduate students’ realities and experiences, and the ways in which (whaka)whanaungatanga has been fluid during the COVID-19 pandemic and lockdowns. This discussion highlights the resourcefulness of Indigenous postgraduate students and the ways in which we operate from spaces of aroha ki te tangata. © 2020, Nga Pae o te Maramatanga. All rights reserved.

ERYTHEMA NODOSUM-LIKE RASH AFTER SARS-COV-2 VACCINATION: A CASE REPORT

TOPIC: Education, Research, and Quality Improvement TYPE: Medical Student/Resident Case Reports INTRODUCTION: With the rapid emergence of SARS-CoV-2 and the pandemic implications carried forth, the medical community continues to improve vaccination efforts while monitoring potential side effects not initially considered. Erythema nodosum is known as a delayed-type hypersensitivity reaction with a pathophysiology not yet fully understood.1 Its classic presentation is diagnosed clinically by noting painful erythematous nodules on the bilateral lower extremities notably in the calves and shins. The condition is typically self-limiting. We present a case of erythema nodosum evoked by the SARS-CoV-2 Moderna vaccine. CASE PRESENTATION: A 44-year-old Caucasian female with no significant past medical history presented to the emergency department (ED) at a community hospital with progressively worsening lower extremity rash. The rash started 7 days after the second administered dose of the SARS-CoV-2 vaccine (Moderna series). Prior to ED presentation, she had been seeing her primary care physician for her ongoing symptoms. Her vital signs in the emergency department were stable. Physical examination was benign other than multiple, tender, non-blanchable 6-8 cm erythematous nodules present on the bilateral calves and shins. Laboratory findings from her primary care physician's office noted negative ANA, rheumatoid factor, ESR, thyroid panel, upper respiratory viral panel including SARS-CoV-2, complete blood count, comprehensive metabolic profile, and coagulation PT-INR times. Her only notable finding was an elevated c-reactive protein of 23.5 mg/L. She was discharged from the ED and continued supportive care with nonsteroidal anti-inflammatory drugs. DISCUSSION: As SARS-CoV-2 vaccinations continue global administration, it becomes imperative to recognize and document noted adverse effects. This will allow education of potential side effects and lessen public fear from getting vaccinated. Cutaneous reactions are common enough to be noted from a variety of etiologies including infection, drugs, autoimmune processes and other disease and non-disease states. Specifically, erythema nodosum has been documented in the medical literature as sequela to SARS-CoV-2 infection.2 It has yet to be documented as a reaction to the vaccine. This presenting dermatologic pattern was of concern to the patient but should be recognizable to clinicians as self-limiting.3 Further citations of various presentations will continue to improve the characterization of the ongoing pandemic environment. CONCLUSIONS: As SARS-CoV-2 vaccination efforts continue on a global scale, it is important that both clinicians and patients have access to potential side effect manifestations and education. This will help reassure patients and the public in the safety of vaccine administration despite possible self-limiting cutaneous manifestations. It will also help improve navigation of the current healthcare landscape as more people get vaccinated. REFERENCE #1: Criado, Paulo Ricardo, et al. "Are the cutaneous manifestations during or due to SARS-CoV-2 infection/COVID-19 frequent or not? Revision of possible pathophysiologic mechanisms." Inflammation Research 69 (2020): 745-756. https://link.springer.com/content/pdf/10.1007/s00011-020-01370-w.pdf REFERENCE #2: Galvan Casas C, Catala A, Carretero Hernandez G, et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases [published online ahead of print, 2020 Apr 29]. Br J Dermatol. 2020;https://doi.org/10.1111/bjd.19163. REFERENCE #3: Inamadar AC, Adya KA. The rash with painful and erythematous nodules. Clin Dermatol. 2019 Mar-Apr;37(2):129-135. doi: 10.1016/j.clindermatol.2018.12.006. Epub 2018 Dec 5. PMID: 30981293. DISCLOSURES: No relevant relationships by Martin Herrera, source=Web Response No relevant relationships by Heather Holstein, source=Web Response No relevant relationships by Kathryn West, source=Web Response

COVID-19 antibodies in convalescent plasma evaluated by the C19-kodecyte (Anti-SARSCoV- 2 Red Cell) Assay

Background/Case Studies: We had developed a simple and rapid red cell agglutination assay for serologic screening of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated this new C19-kodecyte assay in a cohort of convalescent patients with PCR-confirmed SARS-CoV-2 infection and compared its analytical performance with three established assays. Study Design/Methods: Red cells modified with peptides from SARS-CoV-2 spike protein using the Kode Technology were prepared.We tested plasma samples from 140 convalescent plasma donors and 125 healthy donors that had tested negative for anti-SARS-CoV-2 Total (Ortho). Plasma samples were stored at -30 °C before testing. Testing was performed using the column agglutination technology commonly employed for blood typing. The results were evaluated and compared with the results of a virus neutralization assay and two commercial chemiluminescent antibody tests: Ortho anti-SARS-CoV-2 Total (IgG, IgM and IgA) assay and Ortho anti-SARS-CoV-2 IgG antibody assay. Results/Findings: The median time interval from the onset of symptoms and plasma donation was 94 days (range: 33 - 331 days). Our simple and rapid C19-kodecyte assay detected SARS-CoV-2 antibodies with a specificity of 95.2% and sensitivity of 92.1%. Correlation analysis of measurement data among the different platforms showed a weak to moderate concordance. The Pearson correlation coefficient ranged between 0.21 and 0.28 for C19-kodecyte versus Ortho anti-SARS-CoV-2 Total and Ortho anti-SARS-CoV-2 IgG assays while it was 0.24 between C19-kodecyte and neutralizing titer. Agreements among C19-kodecyte versus Ortho anti-SARS-CoV-2 Total and Ortho anti-SARS-CoV-2 IgG assays were moderate: 0.41 (0.09-0.73) and 0.41 (0.14-0.68), respectively. Conclusions: Sensitivity and specificity of the C19-kodecyte assay are within the estimated range of FDA issued EUA authorized serology tests (88% to 100% sensitivity and 95% to 100% specificity). The low correlation between C19-kodecyte versus Ortho anti-SARSCoV- 2 results and between C19-kodecyte versus neutralizing titer suggests that COVID-19 patients develop a broad antibody repertoire against multiple SARS-CoV-2 proteins and epitopes and different assays detect diverse antibody specificities. Our easily scalable approach using C19-kodecytes can be operated in blood typing laboratories worldwide using common routine setups. The availability of standard blood group serology techniques for SARS-CoV-2 antibody screening could vastly improve assay capacity. This would be particularly useful in developing countries, where dedicated virology and microbiology may be lacking the necessary turnaround capacity.

Serological assays and neutralizing activity in COVID-19 convalescent plasma donors

Background/Case Studies: In the absence of definitive treatment, plasma from convalescent donors is an investigational therapeutic option for COVID-19, caused by the virus SARS-CoV-2. We investigated total (Immunoglobulins A, M, and G), Immunoglobulin G and in vitro neutralizing anti-SARS-CoV-2 antibody titers in COVID-19 Convalescent Plasma (CCP) Donors. Study Design/Methods: We recruited donors who had laboratory evidence of past COVID-19 infection and recovery from COVID-19 for ≥ 28 days. Female donors were tested for HLA antibodies. All donor samples were tested for Anti-SARS-CoV-2 antibodies using the Ortho- Clinical Diagnostics VITROS Total and IgG COVID-19 Antibody Test, a qualitative (semi-quantitative) chemiluminescent CLIA immunoassay (EUA) targeting SARSCoV- 2 antigen subunit 1 [S1] of the spike protein and an in-house plaque reduction neutralizing test (PRNT). Results/Findings: We tested samples from 117 donors, mean age 46.9 ± 14.3 years, F:M=1.25:1;most (92.3%) had mild symptoms of COVID-19. ABO blood groups were O (34.2%), A (35.9%), B (12.8%), and AB (6.8%);30.7% of females had HLA antibodies. At initial presentation, total Anti-SARS-CoV-2 Ab, IgG Ab alone and presence of neutralizing activity were detected in 98.3%, 90.6%, and 82.9% of donors respectively. Neutralizing antibodies were detected in 84.9% (90/106) of IgG Ab positive donors. IgG Ab levels (S/Co) were positively correlated with Total Ab levels (R2=0.66, p <0.0001). IgG Ab levels showed a high degree of correlation with the neutralizing Ab titers (one-way ANOVA p <0.0001). Twentyeight (23.9%) donors presented for repeat donation, after a median interval of 37 days (range 21-72). On repeat presentation, total Ab level increased in 81.5% and IgG Ab decreased in 74.1% of donors;neutralizing Ab titers decreased in 44.4% and remained unchanged in 33.3% of repeat donors. There was no correlation observed between total Ab levels and number of days postsymptom onset (R2 = 0.09). Total Ab and IgG Ab levels were significantly different based on degree of symptomseverity (p = 0.019 and 0.022, respectively), with statistically significant differences between asymptomatic and severe cases (p = 0.041 and 0.030, respectively). There was no correlation between Total Ab, IgG Ab, or neutralizing Ab titers with age, sex, ABO blood group or HLA antibody status. Conclusions: 98% of CCP donors had detectable anti- SARS-CoV-2 antibody, and 83% had neutralizing antibodies. IgG Ab correlated strongly with neutralizing Ab titers. On repeat presentation, neutralizing Ab titers decreased in 44.4%, and remained unchanged in 33%.

Contingency planning for COVID-19: Feasibility of twice weekly hemodialysis in a large canadian cohort

Background: Reducing hemodialysis treatments from three times weekly to twice weekly is a potential strategy to lessen potential exposure/transmission of COVID-19 while allowing hemodialysis units to operate with fixed/reduced resources. As part of contingency planning at a large Canadian center, all facility-based hemodialysis patients were reviewed in advance for candidacy of a reduced 'twice weekly' schedule. Methods: All prevalent patients receiving at least thrice weekly, facility-based hemodialysis - affiliated with the QEII Halifax, Nova Scotia, Canada - were systematically reviewed in a stepwise manner, using accepted criteria for implementing twice weekly hemodialysis (Fig. 1). Results: Of 473 patients assessed, only 18 (4%) fulfilled criteria for twice weekly hemodialysis (Fig 1.) Of these patients, average age was 63 ± 12 (SD) years, 61% were diabetic, 95% Caucasian;and at least 67% receiving dialysis for 6+ months prior to assessment. 83% of qualifying patients missed 0 treatments in the preceding month, and none missed >1 treatment. Average for serum albumin was 36 ± 4 g/L, Urea reduction ratio, 72.7, and residual urea clearance, 5.7 ± 2.7 mL/min/1.73m2. Conclusions: Although feasible, a twice weekly hemodialysis strategy applied to a small proportion of our patient population, potentially reflecting an 'intention to defer' strategy for initiating dialysis.