The temporal evolution in disease phenotype of COVID-19 hospitalisation, intensive care and case fatality rates in cancer patients across the United Kingdom (UKCCP)

Background: People living with cancer are reported to be at increased risk of hospitalization and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is proposed to be dependent on a combination of intrinsic patient and cancer factors such as cancer subtype, and emerging SARS-CoV-2 variants with differing pathogenicity. However, COVID-19 phenotype evolution across the pandemic from 2020 has not yet been systematically evaluated in cancer patients. Method(s): This study is a population-scale real-world evaluation of Coronavirus outcomes in the United Kingdom for cancer patients from 1st November 2020-31st August 2022. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years old. Case-outcome rates, including hospitalization, intensive care and casefatality rates were used to assess the evolution in disease phenotype of COVID-19 in cancer patients. Multivariable logistic regression models were fitted to compare risk of Coronavirus outcomes in the cancer cohort relative to the non-cancer population during the Omicron wave in 2022. Result(s): The cancer cohort comprised of 198,819 positive SARS-CoV-2 tests from 127,322 individual infections. Coronavirus case-outcome rates were evaluated by reference to 18,188,573 positive tests from 15,801,004 individual infections in the non-cancer population. From 2020 to 2022, the SARS-CoV-2 disease phenotype became less severe in both patients with cancer and the non-cancer population, though cancer patients remain at higher risk. In 2022, the relative risk of Coronavirus hospital admission, inpatient hospitalization, intensive care admission and mortality in cancer patients was 3.02x, 2.10x, 2.53x and 2.54x compared to the non-cancer population following multivariable adjustment, respectively. Higher risk of hospital admission and inpatient hospitalization were associated with receipt of B/T cell antibody and/or targeted therapy which also corresponded with an increased risk of Coronavirus mortality. Conclusion(s): The disease phenotype of SARS-CoV-2 in cancer patients in 2022 has evolved significantly from the disease phenotype in 2020. Direct effects of the virus in terms of SARS-CoV-2 hospitalization, intensive care and case fatality rates have fallen significantly over time. However, relative to the general population, people living with cancer and hematological malignancies remain at elevated risk. In order to mitigate the indirect effects of the SARS-CoV-2 pandemic in terms of disruption to cancer care, there should be increased focus on preventative measures. Used in conjunction with vaccination and early treatment programs, this will maximize quality of life for those with cancer during the ongoing pandemic and ensure the best cancer outcomes.

Resilience in adolescence during the COVID-19 crisis in Canada.

BACKGROUND: The COVID-19 pandemic constitutes a social crisis that will have long-term health consequences for much of the global population, especially for adolescents. Adolescents are triply affected as they: 1) are experiencing its immediate, direct effects, 2) will carry forward health habits they develop now into adulthood, and 3) as future parents, will shape the early life health of the next generation. It is therefore imperative to assess how the pandemic is influencing adolescent wellbeing, identify sources of resilience, and outline strategies for attenuating its negative impacts. METHODS: We report the results of longitudinal analyses of qualitative data from 28 focus group discussions (FGDs) with 39 Canadian adolescents and of cross-sectional analyses of survey data from 482 Canadian adolescents gathered between September 2020 and August 2021. FGD participants and survey respondents reported on their: socio-demographic characteristics; mental health and wellbeing before and during the pandemic; pre- and during-pandemic health behaviours; experiences living through a crisis; current perceptions of their school, work, social, media, and governmental environments; and ideas about pandemic coping and mutual aid. We plotted themes emerging from FGDs along a pandemic timeline, noting socio-demographic variations. Following assessment for internal reliability and dimension reduction, quantitative health/wellbeing indicators were analyzed as functions of composite socio-demographic, health-behavioural, and health-environmental indicators. RESULTS: Our mixed methods analyses indicate that adolescents faced considerable mental and physical health challenges due to the pandemic, and were generally in poorer health than expected in non-crisis times. Nevertheless, some participants showed significantly better outcomes than others, specifically those who: got more exercise; slept better; were food secure; had clearer routines; spent more time in nature, deep in-person social relationships, and leisure; and spent less time on social media. CONCLUSIONS: Support for youth during times of crisis is essential to future population health because adolescence is a period in the life course which shapes the health behaviours, socio-economic capacities, and neurophysiology of these future parents/carers and leaders. Efforts to promote resilience in adolescents should leverage the factors identified above: helping them find structure and senses of purpose through strong social connections, well-supported work and leisure environments, and opportunities to engage with nature.

COVID-19 disease modifying treatment guideline adherence in Western Australia

Introduction/Aim: Western Australia had its first wave of COVID-19 cases in March 2022. This retrospective study assessed the adherence to guidelines for prescribing COVID-19 disease modifying therapies (DMT), based on the National COVID-19 Clinical Evidence Taskforce Australian guidelines for the clinical care of people with COVID-19. Method(s): The first 100 cases admitted to the respiratory ward at Fiona Stanley Hospital (FSH) with confirmed COVID-19 were reviewed. Data was collected from the hospital Digital Medical Record to determine clinical severity on presentation and the need for DMT. Prescribing of DMT was assessed for adherence against the National guidelines and/or whether it was recommended by the infectious diseases (ID) team. Disease progression, length of stay, mortality and readmission rates were assessed within 28 days of admission. Result(s): During the audit period (11.03.2022 - 19.04.2022), the National guidelines underwent six updates. In the first 100 cases of COVID-19, the median (IQR) age was 65.11 years, the median (IQR) length of stay was 4 days and the mortality rate was 1%. There was a 7% readmission rate with 6% of patients treated with DMT having disease progression. 16% of patients were immunocompromised and 58% were partially vaccinated or unvaccinated. 63% of unvaccinated patients had severe disease. 84% of patients were recommended a DMT, of which, 63% received the correct combination of DMT. 14% of cases were recommended and not prescribed a DMT, though 71% of these cases were recommended budesonide alone. 12% were not recommended and not prescribed a DMT and 4% were not recommended, yet prescribed a DMT. Conclusion(s): Overall adherence with the National guidelines/ID advice for DMT was >80% excluding inhaled budesonide. The continually evolving nature of the National guidelines added complexity to prescribing. A dedicated medical proforma would aid with risk stratification and DMT prescribing for patients with COVID-19.

Procalcitonin and D-dimer levels at baseline, but not CRP, were informative of COVID-19 hospitalization outcomes

Background. The WHO estimates 512 million cases of COVID-19 and 6.2 million deaths globally as of May 4th, 2022. In Michigan (MI), the first case was diagnosed March 10th, 2020. We describe here outcomes of COVID-19 patients cared for in a large tertiary hospital in 2020 spanning two surges based on baseline lab values for C-reactive protein (CRP), Procalcitonin (PC), and D-Dimer (DD). Methods. After IRB approval, adult patients diagnosed via PCR with COVID-19 during the two surges in 2020 and admitted to Beaumont Hospital, Royal Oak, an 1,131 beds tertiary care referral center in MI, were reviewed. Demographic, clinical and laboratory characteristics were obtained from the EMR. ICD-10 classification diagnoses were utilized to identify comorbidities, and patient BMIs were based on the admission values in the EMR. Outcomes were defined as death during current admission, transfer to nursing home or other facility, or discharge home. Using a tree-based model and the combined levels of the three labs we defined a hierarchy of four lab levels, each progressively having increased risk of death. We then analyzed the outcome for the four levels, adjusting for time period (surge), age, sex, race, BMI and comorbidities. Data was analyzed using SAS statistical software version 9.4 (SAS Institute). Results. A total of 2197 patients were identified from March through December 2020, of whom 1118 had CRP, PC and DDavailable at baseline. The mean age was 66.7 years (SD 16.1) for the cohort in first surge (March-June), and 66.4 (15.6) in the latter surge (July-December, Table1). More patients had a PC of >0.5 in the first surge (25.7%) than the second (13.2%). After adjusting for all other factors, the hierarchical lab levels are significantly associated with outcomes. Of note, baseline CRP value was not informative. Compared to the 2nd level (Table 2), the lowest level (PC < 0.1) has significantly lower odds of death [OR=0.37, 95% CI (0.19, 0.73)], while the highest level, (DD >1000 and PC >= 0.26) has significantly higher odds of death [OR=3.01, 95% CI (1.59, 5.72)]. Conclusion. Baseline PC and DD, but not CRP, were informative in determining risk of death and can assist clinicians determine possible outcomes during COVID-19 hospitalization.

Development of an international COVID-19 specific healthrelated quality of life questionnaire, phase III pretesting and validation

Aims: This study aimed to develop, pilot-test and psychometrically analyse a patient-reported health-related quality of life questionnaire for patients with current or previous coronavirus disease (COVID-19). A disease-specific instrument was not available before, even though the patients experience a wide range of symptoms and reduced functioning. Method(s): We used an internationally recognized methodology for questionnaire development consisting of four phases. Adults with current or previous COVID-19, in hospital, nursing home or at home were eligible. In phase I, relevant issues were gathered through literature review, interviews with health-care workers and patients, and operationalized into items in phase II. In the current study, participants completed the questionnaire and were interviewed as part of phase IIIA and, in phase IIIB, participants completed a revised questionnaire and a debriefing form. Validity and reliability were assessed by correlation-based methods, Cronbach's alpha and intra-class correlation coefficient. Result(s): We enrolled participants from 11 countries within and outside Europe, 54 in phase IIIA and 371 in Phase IIIB. The mean time needed to complete the 80-item questionnaire in Phase IIIA was 16 min (range 4-45). Predefined criteria for retention were fulfilled for 71 items of which five needed some rewording. In phase IIIB, 80% of participants completed the 71-item questionnaire within 15 min, on paper (n = 175) or digitally (n = 196). The final questionnaire includes 61 items that fulfilled criteria for retention or were important to subgroups of patients. The item-scale correlations were>0.7 for all but nine items;three of these were changed. The internal consistency (alpha range 0.68-0.92) and test-retest (all but one scale>0.7) results were acceptable. The final scale structure of the Oslo COVID-19 quality of life (QLQ) weekly (W) 61 consists of 15 multi-item scales and six single items covering e.g. acute and long-term physical symptoms, psychological distress, and physical, social functioning. Patient representatives expressed satisfaction with the content of the questionnaire. Conclusion(s): COVID-19 is a disease with a pleomorphic symptomatology. In addition to many items assessing symptoms, multiple functional items were included. The Oslo COVID-19 QLQ-W61 is a cross-cultural instrument, now ready for use in research and clinical practice.

Pancreas and islet transplantation in the United Kingdom during the COVID-19 era

Introduction: WHO declared a pandemic of COVID-19 in March 2020. This study analyses the impact of COVID-19 on beta-cell replacement therapy in the UK. Method(s): Pancreas and islet donation and transplant activity in the period March 2020/2021 was compared with the same period the previous year. Result(s): 2,180 patients had a functioning graft during March 2020/2021. 5.8%(n=126) tested positive for COVID-19 and two died (1%). In this period there was a 43% reduction in solid organ donors n=1,615, compared with the previous year, n=2,840. Of the 625 solid organ donors with a pancreas offered, 32% had the pancreas retrieved compared with 51% the previous period. 97 whole pancreas and islet transplants were performed in the UK down 54% from the prior period. Of the 84 pancreas transplant recipients;four tested positive for COVID-19 but none died, and two grafts failed within the first week from vascular thrombosis (neither were COVID-19 positive). Of the 13 SIK and islet alone transplant recipients, two tested positive for COVID-19 but neither died. Of these SIK transplants, one is known to have failed within a month and this is equivalent to that seen in the previous time period. To our knowledge, no patient receiving beta cell replacement therapy died of COVID during the first year of the pandemic despite immunosuppression. Conclusion(s): In the UK, pancreas, and islet transplantation have continued during the pandemic at a lower rate. Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior. Take-home message: Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior.

Isolation of SARS-CoV-2-blocking recombinant antibody fragments and characterisation of their binding to variant spike proteins

COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2. From its initial appearance in Wuhan, China in 2019, it developed rapidly into a global pandemic. In addition to vaccines, therapeutic antibodies play an important role in immediately treating susceptible individuals to lessen severity of the disease. In this study, phage display technology was utilised to isolate human scFv antibody fragments that bind the receptor-binding domain (RBD) of SARS-CoV-2 Wuhan-Hu-1 spike protein. Of eight RBD-binding scFvs isolated, two inhibited interaction of RBD with ACE2 protein on VeroE6 cells. Both scFvs also exhibited binding to SARS-CoV-2 Delta variant spike protein but not to Omicron variant spike protein in a Raman spectroscopy immunotest. The study demonstrates the potential of recombinant antibody approaches to rapidly isolate antibody moieties with virus neutralisation potential. Copyright © 2022 Antoine, Mohammadi, McDermott, Walsh, Johnson, Wawrousek and Wall.

CNN Architecture for Lung Cancer Detection

Lungs play major role for the respiratory rate in a human being. Lung cancer can be detected only after the disease spreads to neighboring parts and hence detecting lung cancer in initial stage is difficult. Even in covid-19, lung gets affected as it deals with respiration which is the first symptom in serious covid conditions. In this paper, we have proposed a method to detect the lung cancer which involves feature extraction and ML algorithm or in another way using CNN architecture which is a DL algorithm helps in lung cancer detection. As the methods deal with binary classification which confirms yes/no of the lung cancer presence in human body, both SVM and CNN methods are simpler than any other ML/DL algorithms for this lung cancer data considered. Simulations are carried out in google colab. Feature extraction is carried out for ML algorithm and bar graph, histograms are plotted. © 2022 IEEE.

Quantitative MRI findings indicate diffuse white matter damage in Susac Syndrome.

BACKGROUND: Susac Syndrome (SuS) is an autoimmune endotheliopathy impacting the brain, retina and cochlea that can clinically mimic multiple sclerosis (MS). OBJECTIVE: To evaluate non-lesional white matter demyelination changes in SuS compared to MS and healthy controls (HC) using quantitative MRI. METHODS: 3T MRI including myelin water imaging and diffusion basis spectrum imaging were acquired for 7 SuS, 10 MS and 10 HC participants. Non-lesional white matter was analyzed in the corpus callosum (CC) and normal appearing white matter (NAWM). Groups were compared using ANCOVA with Tukey correction. RESULTS: SuS CC myelin water fraction (mean 0.092) was lower than MS(0.11, p = 0.01) and HC(0.11, p = 0.04). Another myelin marker, radial diffusivity, was increased in SuS CC(0.27µm2/ms) compared to HC(0.21µm2/ms, p = 0.008) and MS(0.23µm2/ms, p = 0.05). Fractional anisotropy was lower in SuS CC(0.82) than HC(0.86, p = 0.04). Fiber fraction (reflecting axons) did not differ from HC or MS. In NAWM, radial diffusivity and apparent diffusion coefficient were significantly increased in SuS compared to HC(p < 0.001 for both measures) and MS(p = 0.003, p < 0.001 respectively). CONCLUSIONS: Our results provided evidence of myelin damage in SuS, particularly in the CC, and more extensive microstructural injury in NAWM, supporting the hypothesis that there are widespread microstructural changes in SuS syndrome including diffuse demyelination.

Proficiency testing and ring trials.

The validation of diagnostic methods (and the subsequent results generated by a laboratory) are improved through participation in inter-laboratory comparisons (IC), such as proficiency-testing (PT) programmes and other exercises referred to as 'ring tests' or 'ring trials' (RTs). This is a requirement to comply with international quality standards. Validating a method is a continuous process and taking part in ongoing PT programmes supports the management of a method's life cycle, providing continuing assessment of fitness (sometimes referred to as the 'validation retention status'). Proficiency-testing panel designs ensure that the methods used, particularly diagnostic specificity and sensitivity, are suitably challenged. Appraising PT results over time can illustrate whether the laboratory's performance is stable, improving or worsening, and proficiency tests can also highlight variations in the performance of assays. The development of new proficiency tests can support the implementation of novel diagnostics technologies, such as whole genome sequencing and point-of-care testing, and assist in cross-sectoral partnerships focusing on One Health approaches, which are high on the agenda for infectious disease control. For example, the rapid design and distribution of emergency exempted assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) means that these assays were not as rigorously evaluated as assays for established infectious diseases. Therefore, participation in PT programmes for SARS-CoV-2 is essential to understand the performance of these assays. While other mechanisms help to underpin laboratory activities, PT has been, and should remain, an integral part of laboratory quality assurance. Resources must be directed towards increasing and improving the quality of PT (for example, availability and accessibility of suitable biological and reference materials are essential for a PT provider to execute its duties), to support established and novel methods such as genomic and point-of-care tests.

Les procédures de validation des méthodes de diagnostic (et les résultats obtenus par la suite par les laboratoires) peuvent être améliorées en participant à des comparaisons inter-laboratoires, sous forme notamment de programmes d'aptitude inter-laboratoires ou d'autres exercices désignés collectivement sous l'appellation d'essais comparatifs inter-laboratoires (ring trials en anglais). Cette participation constitue une obligation au regard de la conformité avec les normes internationales de qualité. La validation d'une méthode est un processus continu et la participation à des programmes d'aptitude inter-laboratoires offre des garanties quant à la gestion du cycle de vie de la méthode considérée, car elle se traduit par une évaluation continue de l'aptitude à l'emploi du test (également désignée comme la « conservation de son statut de validation ¼). Les panels des essais d'aptitude sont conçus de manière à garantir que les méthodes utilisées font l'objet d'essais appropriés, en particulier concernant leur spécificité et sensibilité diagnostiques. L'appréciation des résultats des essais d'aptitude dans le temps permet d'établir si les performances d'un laboratoire restent stables, s'améliorent ou se dégradent ; les essais d'aptitude mettent également en lumière les éventuelles variations dans les performances d'un essai. La mise au point de nouveaux essais d'aptitude peut encourager l'utilisation de technologies de diagnostic innovantes, par exemple le séquençage du génome entier et les tests utilisables sur le lieu des soins, et faciliter les partenariats intersectoriels axés sur des approches Une seule santé, qui figurent parmi les grandes priorités en matière de lutte contre les maladies infectieuses. Par exemple, la conception et la distribution rapides de tests de détection du coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) suivant un protocole d'exception imposé par l'urgence signifient que ces tests n'ont pas fait l'objet d'une évaluation aussi rigoureuse que les tests de détection de maladies infectieuses bien établies. Par conséquent, la participation à des programmes d'essais d'aptitude pour le SARS-CoV-2 est essentielle pour déterminer précisément les performances de ces tests. S'il existe d'autres mécanismes permettent d'étayer les activités d'un laboratoire, les essais d'aptitude ont été et doivent continuer à être une partie intégrante de l'assurance qualité des laboratoires. Il convient d'affecter des ressources à l'accroissement du nombre d'essais d'aptitude et à l'amélioration de leur qualité (il est notamment essentiel que les fournisseurs de tests d'aptitude puissent se procurer facilement des matériels biologiques et réactifs de référence appropriés afin de mener à bien leur tâche), de manière à soutenir aussi bien les méthodes classiques que celles qui procèdent d'innovations comme les tests génomiques et ceux utilisables sur le lieu des soins.

La validación de métodos de diagnóstico (y de los subsiguientes resultados obtenidos por un laboratorio) mejora con la participación en procesos de comparación entre laboratorios, como pueden ser los programas de pruebas de competencia u otros procesos denominados globalmente "pruebas interlaboratorios". Se trata de un requisito de obligado cumplimiento según dictan las normas internacionales de calidad. La validación de un método es un proceso permanente y, en este sentido, el hecho de tomar parte en programas continuos de pruebas de competencia ayuda a gestionar un método de prueba durante todo su ciclo de vida, aportando en todo momento una evaluación de su nivel de idoneidad (lo que a veces se denomina también el "estado de retención de la validación"). El diseño de paneles de pruebas de competencia sirve para garantizar que los métodos empleados, y en particular su especificidad y sensibilidad de diagnóstico, sean convenientemente evaluados. El análisis de los resultados de pruebas de competencia a lo largo del tiempo puede indicar si el laboratorio se mantiene en niveles estables de rendimiento o si este mejora o empeora. Las pruebas de competencia también pueden poner de manifiesto variaciones en el rendimiento de un ensayo. La creación de nuevas pruebas de competencia puede contribuir a la implantación de novedosas tecnologías de diagnóstico, como la secuenciación de genoma completo o las pruebas practicadas en el punto de consulta, y ayudar a trabajar en alianzas intersectoriales desde planteamientos en clave de "Una sola salud", extremo este de lo más prioritario en los planes de lucha contra las enfermedades infecciosas. Valga como ejemplo la celeridad con que se han concebido y distribuido ensayos aplicables al coronavirus del síndrome respiratorio agudo severo de tipo 2 (SARS-CoV-2), con las exenciones propias de un procedimiento de urgencia, lo que supone que estos ensayos no hayan pasado por un proceso de evaluación tan riguroso como el que se aplica a patógenos infecciosos más antiguos. Por ello, en el caso concreto del SARS-CoV-2, la participación en programas de pruebas de competencia es fundamental para aprehender el rendimiento que ofrecen estos ensayos. Si bien hay otros mecanismos que ayudan a reforzar el trabajo de laboratorio, las pruebas de competencia han sido, y deben seguir siendo, parte integrante de la garantía de calidad que ofrece un laboratorio. Para potenciar el uso de métodos ya arraigados o novedosos, como puedan ser la genómica o las pruebas en el punto de consulta, es preciso dedicar recursos a la realización de un mayor número de pruebas de competencia de mejor calidad (la existencia de material biológico y de referencia adecuado y la facilidad de acceso a él, por ejemplo, son sendos factores básicos para que un proveedor de pruebas de competencia pueda cumplir su cometido).

Teachers' Organizations Responses to COVID-19 in Canada: Balancing Resistance, Rapprochement, and Renewal

Teacher federations are often criticized as "roadblocks" to educational change. It is arguable, however, that their advocacy work has been paramount in securing safer return to school conditions across Canadian Educational jurisdictions. Utilizing Carter et al. (2010) framework of union responses to changing policy environments, this paper draws on publicly available documents and social media posts from March through to October of 2020 to examine the ways in which teacher unions in various Canadian contexts have responded to the issue of school reopening plans amid the COVID-19 pandemic. In particular, the paper analyzes the extent to which Canadian teacher unions have been able to move into the realm of union renewal as a means of building internal capacity and developing external networks to strengthen their public advocacy work.

POSC243 Systemic Challenges in Tele-Health and Structural Solutions to Enhance Access

Objectives: In light of the transition to virtual healthcare, this study's aims were to (i) characterize disparities in access to virtual care services during the COVID-19 pandemic compared to conventional care and (ii) propose decision-making interventions to enhance access based on common themes identified in current literature. Methods: We conducted a qualitative review and thematic analysis of literature adhering to ENTREQ guidelines, utilizing PubMed/Medline, EMBASE, and Google Scholar databases to examine studies from March 2020 (defined as pandemic onset) to present evaluating disparities in accessing virtual care during the pandemic. Keywords used in our search included: "socioeconomic", "disparity", "telemedicine", "tele-health", "virtual consults", and "vulnerable populations". Results: We identified 21 studies classifying five major themes, including geographical, social, economic, generational, and racial/demographic-based. All included studies comprised of data collected through surveys or interviews of patient cohorts. Of these, many demonstrated parallels to in-person healthcare access(18/21), determining systemic racial factors(13/21), socioeconomic inequities(10/21), and limitations in rural access to care(8/21). Three determined generational gaps in digital literacy were poor predictors of access to virtual care and that geographical proximity was linked to access. Indigenous, Asian, non-English speaking, ethnic minorities, and lower socioeconomic status individuals were less likely to use virtual, compared to in-person healthcare. We noted these factors reflected complex structural systems and personal circumstances access to virtual care did not address. Based on this data, we propose (i) the formation of centralized clinical networks consisting of low-resource medical centres and larger urban centres such as tertiary care facilities and (ii) the creation of a digital decision algorithm, where vulnerable patient populations are matched with high-resource centres with the adequate support and tools required. Conclusions: Current evidence suggests sustained disparity among already vulnerable groups owing to inherent institutional flaws present in healthcare, suggesting the need for patient- and systems-level intervention to enhance access.

Humoral and cellular immunogenicity of SARS-CoV-2 vaccines in chronic lymphocytic leukemia: a prospective cohort study.

Chronic lymphocytic leukemia (CLL), the most common leukemia worldwide, is associated with increased COVID-19 mortality. Previous studies suggest only a portion of vaccinated CLL patients develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies. Whether the elicited antibodies are functional and/or accompanied by functional T-cell responses is unknown. This prospective cohort study included patients with CLL who received SARS-CoV-2 and PCV13 vaccines (not concurrently). The primary cohort included adults with CLL off therapy. Coprimary outcomes were serologic response to SARS-CoV-2 (receptor binding domain [RBD] immunoassay) and PCV13 vaccines (23-serotype IgG assay). Characterization of SARS-CoV-2 antibodies and their functional activity and assessment of functional T-cell responses was performed. Sixty percent (18/30) of patients demonstrated serologic responses to SARS-CoV-2 vaccination, appearing more frequent among treatment-naïve patients (72%). Among treatment-naïve patients, an absolute lymphocyte count ≤24 000/µL was associated with serologic response (94% vs 14%; P < .001). On interferon-γ release assays, 80% (16/20) of patients had functional spike-specific T-cell responses, including 78% (7/9) with a negative RBD immunoassay, a group enriched for prior B-cell-depleting therapies. A bead-based multiplex immunoassay identified antibodies against wild-type and variant SARS-CoV-2 (α, ß, γ, and δ) in all tested patients and confirmed Fc-receptor binding and effector functions of these antibodies. Of 11 patients with negative RBD immunoassay after vaccination, 6 (55%) responded to an additional mRNA-based vaccine dose. The PCV13 serologic response rate was 29% (8/28). Our data demonstrate that SARS-CoV-2 vaccination induces functional T-cell and antibody responses in patients with CLL and provides the framework for investigating the molecular mechanisms and clinical benefit of these responses. This trial was registered at www.clinicaltrials.gov as #NCT05007860.

Sars-Cov-2 Antibody Levels in Blood Cancer Patients after a Third Sars-Cov-2 “Booster” Vaccination - Observational Data from the LLS National Registry

Immunosuppressed patients may be at high risk for breakthrough COVID-19 infection despite SARS-CoV-2 vaccination, due to an inadequate or negligible antibody response. Based on data from the Leukemia & Lymphoma Society (LLS) National Registry, 25% of patients with hematologic malignancies do not produce anti-Spike protein antibodies in response to mRNA vaccines, with B-cell malignancy patients at highest risk (Greenberger et al, 2021, Cancer Cell, on-line). While studies of T-cell immunity, antibody cocktails, and booster vaccinations are underway, some patients have elected to receive an additional “booster” vaccination after a full course of SARS-CoV-2 vaccination. The LLS National Registry (NCT04794387) has collected Patient Reported Outcomes and serology from 3300 patients with hematologic malignancies. This study was approved by the Western Institutional Review Board, and participants provided informed consent electronically. As of July 2021, the Registry includes 24 patients who obtained a 3 rd vaccination after full vaccination with mRNA vaccines. Twenty of these patients were seronegative >14 days post 2 nd vaccination (as measured by the Roche Elecsys assay). Four patients had low positive serology results. All patients were nucleocapsid antibody negative. Patient ages ranged from 51-79 years. Eleven had chronic lymphocytic leukemia (CLL), 7 non-Hodgkin's lymphoma (NHL), 5 Waldenstrom's macroglobulinemia (WM), and 1 multiple myeloma (MM). Six patients were not currently on anti-B cell therapy, 11 had received anti-CD20 therapy (8 within the last 6 months), 6 had received Bruton's tyrosine kinase (BTK) inhibitors within the last 6 months, and 1 patient had recently received chemotherapy. The booster vaccinations were obtained between April and June 2021, 21 to 114 days after completing the initial vaccination series between January and April 2021. Serology was performed 12-61 days post-booster vaccination. Fifteen patients received a heterologous adenovirus vaccine. Four patients received a heterologous mRNA vaccine, 5 patients received a homologous mRNA vaccine. Descriptive results are shown on the following table. All patients (4) who had some level of antibody response to the initial vaccines had an augmented antibody response after a booster (i.e. sero-enhanced). Patients who had prior anti-CD20 often failed to seroconvert after booster vaccination. Only 2 of 8 patients who received anti-CD20 antibody treatment in the 6 months prior to vaccination seroconverted after booster vaccination. Two out of 3 seronegative patients receiving anti-CD20 therapy in the last 2 years (but > 6 months) seroconverted after the booster. One patient with follicular lymphoma who received anti-CD20 therapy in 2019 remained seronegative despite a prolonged duration without therapy. Of the 6 seronegative patients taking BTK inhibitors, 3 seroconverted after the booster. Two of the 3 remaining seronegative patients were taking concomitant anti-CD20 therapy. Of the 4 seronegative patients not currently taking anti-B cell therapy, 3 seroconverted while one patient who currently required intravenous immunoglobulin remained seronegative. A patient currently receiving chemotherapy also did not respond to a booster. In this limited set of patients there was no evident pattern of antibody response amongst patients who received homologous versus heterologous vaccine nor between disease types. While anti-CD20 therapy appeared to reduce antibody response to booster vaccination, there was substantial heterogeneity. Although many patients with B-cell malignancies did not mount a robust response to full mRNA vaccine series, several patients demonstrated an antibody response to the booster vaccination. Clinical trials are needed to further understand who can benefit from a booster strategy as well as define the safety of the approach. The LLS Registry includes collection of Electronic Health Records, which will allow us to more specifically evaluate timing and dosage of boosters, the influence of prior therapeutics, as well as health and safety outcomes to better guide patients and physicians through the COVID-19 pandemic. [Formula presented] Disclosures: No relevant conflicts of interest to declare. OffLabel Disclosure: Booster vaccination (after full vaccination) using BNT162b2, mRNA-1273, or Ad26.COV2.S

Acute kidney injury and mortality risk in older adults with and without COVID-19: Data from gerocovid study

BACKGROUND AND AIMS: Research regarding COVID-19 and acute kidney injury (AKI) in older adults is scarce. We evaluated the risk factors and outcomes of AKI in hospitalized older adults with and without COVID-19. METHOD: Observational study of patients admitted to two geriatric clinics in the Stockholm Region of Sweden during the first wave of the COVID-19 pandemic from March 1st to June 15th 2020. The difference in incidence, risk factors and adverse outcomes for AKI between patients with or without COVID-19 were examined. Odds ratios (ORs) for AKI were obtained from logistic regressions. The hazard ratios (HRs) for the risk of in-hospital death were calculated from Cox proportional hazard regression models. RESULTS: We analyzed 316 older patients hospitalized for COVID-19 and 876 patients for non-COVID-19 diagnoses. The mean age was 8369 years, 57% were women, and mean baseline kidney function as depicted by estimated glomerular filtration rate (eGFR) was 62623 ml/min/1.73m2. AKI occurred in 92 (29%) of patients with COVID-19 vs. 159 (18%) without COVID-19. The severity of AKI was significantly worse in patients with COVID-19 compared with non-COVID patients. The odds for developing AKI were higher in patients with COVID-19 (adjusted OR, 1.70;95% CI, 1.04-2.76), low baseline kidney function [4.19 (2.48-7.05), for eGFR 30 ≥ <60 ml/min/1.73m2, and 20.3 (9.95-41.3) for eGFR <30ml/min/1.73m2], and higher C-reactive protein (CRP) level (OR 1.81(1.11-2.95)). The risk of in-hospital death was highest in patients with COVID-19 and AKI [adjusted HR 23.5, 95% CI (8.75-63.0)], followed by COVID-19 without AKI [9.10 (3.52-23.6)] and by patients without COVID-19 and with AKI [6.38 (2.28-17.9)] after adjusting for patient demographics, vital signs, baseline kidney function and medications and using non-COVID patients with no AKI as reference. CONCLUSION: Geriatric patients hospitalized with COVID-19 had a higher incidence of AKI compared with patients hospitalized with other diagnoses. AKI and COVID-19 were associated with in-hospital death. Optimal management of AKI may improve the outcome of COVID-19 in geriatric patients.