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Background: The impact of immunosuppressants on COVID-19 vaccination response and durability in patients with immune-mediated infammatory diseases (IMID) is yet to be fully characterized. Humoral response may be attenuated in these patients especially those on B cell depleting therapy and higher doses of corticosteroids, but data regarding other immunosuppressants are scarce. Objectives: We aimed to investigate antibody and T cell responses and durability to SARS-CoV-2 mRNA vaccines (BNT162b and/or mRNA 1273) in IMID patients on immunomodulatory maintenance therapy other than B-cell depleting therapy and corticosteroids. Methods: This prospective observational cohort study examined the immuno-genicity of SARS-CoV-2 mRNA vaccines in adult patients with IMIDs (psoriatic arthritis, psoriasis, infammatory bowel disease and rheumatoid arthritis) with or without maintenance immunosuppressive therapies (anti-TNF, methotrexate/azathioprine [MTX/AZA], anti-TNF + MTX/AZA, anti IL12/23, anti-IL-17, anti-IL23) compared to healthy controls. Automated ELISA for IgGs to spike trimer, spike receptor binding domain (RBD) and the nucleocapsid (NP) and T-cell release of 9 cytokines (IFNg, IL2, IL4, IL17A, TNF) and cytotoxic molecules (sFasL, GzmA, GzmB, Perforinin) in cell culture supernatants following stimulation with spike or NP peptide arrays were conducted at 4 time points: T1=pre vaccination, T2=me-dian 26 days after dose 1, T3=median 16 days after dose 2 and T4=median 106 days after dose 2. Neutralization assays against four SARS-CoV-2 variants (wild type, delta, beta and gamma) were conducted at T3. Results: We followed 150 subjects: 26 healthy controls and 124 IMID patients: 9 untreated, 44 on anti-TNF, 16 on anti-TNF with MTX/AZA, 10 on anti-IL23, 28 on anti-IL12/23, 9 on anti-IL17, 8 on MTX/AZA (Table 1). Most patients mounted antibody and T cell responses with increases from dose 1 to dose 2 (100% sero-conversion at T3) and some decline by T4, with variability within groups. Antibody levels and neutralization efficacy was lower in anti-TNFgroups (anti-TNF, anti-TNF + MTX/AZA) compared to controls and waned by T4 (Figure 1). T cell responses were not consistently different between groups. Pooled data showed a higher antibody response to mRNA-1273 compared to BNT162b. Conclusion: Following 2 doses of mRNA vaccination there is 100% seroconver-sion in IMID patients on maintenance therapy. Antibody levels and neutralization efficacy in anti-TNF group are lower than controls, and wane substantially by 3 months after dose 2. These fndings highlight the need for third dose in patients undergoing treatment with anti-TNF therapy and continued monitoring of immunity in these patient groups, taking into consideration newer variants and additional vaccine doses.
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Purpose Virtual reality (VR) technology is a potential tool for tourism marketers to maintain the attractiveness of their destinations and recover from the COVID-19 pandemic. However, the effectiveness of VR technology in motivating potential tourists' visit intention under lockdown conditions remains unknown. An integrated model based on the experience economy framework and mood management theory was, therefore, used to explain how tourists' VR experiences affect their mood management processes and subsequent behaviors. This research also examined how perceived travel risk influenced the relationship between mood management processes and future decisions. Design/methodology/approach This study used a cross-sectional design based on a sample collected from a Chinese survey company, Sojump. The author surveyed 285 respondents who had experienced VR tourism activities during the COVID-19 pandemic. The research model was tested using partial least squares-structural equation modeling. Findings The results demonstrated that the four dimensions of VR experiences differently affected mood management processes, while perceived travel risk differently moderated the influence of mood management processes on visit intention and VR stickiness. This provides insights for tourism marketers to adapt to the current tourism environment and develop recovery strategies. Originality/value In response to gaps in the literature, this research examined the effectiveness of VR technology in driving tourists' visit intention during the COVID-19 pandemic, providing insights for tourism marketers to successfully implement VR tourism and plan timely recovery strategies.
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Background: The COVID-19 pandemic has exacerbated multiple barriers to healthcare for vulnerable seniors. They may experience more difficulties in meeting their basic needs for food, medicine, and social support. The objective of the project was to connect with seniors to show our care, to assess food security, medication possession, mental health, and to refer those needing services to appropriate providers. Methods: Using a computer-assisted telephone interview (CATI) approach, we called patients served by our primary care providers from April to December 2020. The CATI assessed their mental health by Personal Health Questionnaire-2 (PHQ2) and General Anxiety Disorder-2 (GAD2). The California Health Place Index (HPI) was used to measure social determinants of health associated with community resources. Descriptive analyses examined the proportion of patients needing follow-up services and being referred to services to address food insecurity (if had <3 days of food), medication needs (if had <30 days of medicine), and mental health services (PHQ2>2 or GAD2>2). Multivariable logistic regression analyses examined demographic and health factors associated with the odds for needing and being referred for follow-up services. Results: Of 1921 respondents, their average age was 76 years (SD11). 52% female and 48% non-female (including male, transgender, and other);74% White, 7% Asian, 7% Hispanic, 3% Black, and 8% other. Medication needs existed among 595 (31%) patients, 196 (10%) faced food insecurity, and 292 (15%) needed mental health services. Regression results suggest, Blacks (OR1.86, p<0.05) had higher odds of being at risk of medication shortage than Whites;Blacks (OR2.30, p<0.05) and Hispanics (OR 2.30, p<0.05) had significantly higher odds of food insecurity than Whites. Higher odds for food insecurity referral were found among non-females (OR7.56, p<0.05) and Blacks (OR10.33, p<0.05). Blacks (OR13.34, p<0.05) and those living in 2nd quartile of HPI (OR2.57, p<0.05) had higher odds for mental health referrals. Conclusions: Significant disparities existed across gender, race, and community resource groups in need for food, medications, and mental health services. Findings underscore the imperatives for health and social services organizations to systematize outreach and follow-up services for vulnerable seniors.
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Introduction: Emerging data suggests that seroresponse (SR) in patients with hematologic malignancy following COVID-19 vaccination is likely lower than in patients without blood cancer. The objective of this study was to perform a systematic review and meta-analysis on SR in patients with hematologic malignancy who received COVID-19 vaccination (submitted to PROSPERO for registration). Methods: We searched PubMed and EMBASE from December 1, 2020, to July 22, 2021, to identify studies of SR following COVID-19 vaccine in adult patients with hematologic malignancy (including studies in which patients with hematologic malignancy represented a subset of a broader population). Patients with positive serologic response at baseline (prior to vaccination) or known COVID-19 infection were excluded. The primary outcomes were pooled SR estimates following COVID-19 vaccination in patients with hematologic malignancy, and pooled SR estimates of subgroups based on hematologic malignancy type. Secondary outcomes were pooled relative risk ratio (RR;compared to non-cancer controls) based on dichotomous-effect SR in all patients, and subgroups based on hematologic malignancy type, treatment status, and use of anti-CD20 therapy. Pooled estimates and RR with its associated 95% confidence intervals (CIs) were calculated using MetaXL (EpiGear), and Reference Manager (Cochrane) using random effects model. Results A total of 17 studies comprising 2834 patients with hematologic malignancy from Europe, United Kingdom and North America were included (Figure 1). The pooled estimate for SR was 58% (95% CI 48-67%, I 2 95%), with a RR of 0.53 (95% 0.42-0.66, I 2 94%) when compared to controls (10 studies with comparison group, 1092 hematologic malignancy patients, 830 controls;Figure 2). The pooled estimate for SR varied by type of hematologic malignancy: lymphomas SR 52% (95% CI 36-68%, 7 studies, 832 patients, I 2 94%);chronic lymphocytic leukemia (CLL) SR 42% (95% CI 25-60%, 6 studies, 921 patients, I 2 93%);plasma cell dyscrasias SR 66% (95% CI 47-83%, 8 studies, 611 patients, I 2 95%);myeloproliferative neoplasms (MPNs, including chronic myelogenous leukemia) SR 83% (95% CI 68-95%, 6 studies, 227 patients, I 2 58%);acute leukemia SR 86% (95% CI 77-94%, 2 studies, 67 patients, 46 acute myelogenous leukemia [AML] and 15 acute lymphocytic leukemia], I 2 0%). The RR for SR also varied by type of hematologic malignancy: lymphomas (excluding CLL) RR 0.48 (95% CI 0.34-0.68, 4 studies, 337 patients, I 2 89%);CLL RR 0.37 (95% CI 0.25-0.53, 3 studies, 194 patients, I 2 54%);plasma cell dyscrasias RR 0.73 (95% CI 0.62-0.86, 5 studies, 323 patients, I 2 70%);RR MPN 0.78 (95% CI 0.62-0.99, 3 studies, 199 patients, I 2 90%). The pooled estimate for SR in those receiving treatment was 42% (95% CI 26-58%, 9 studies, 683 patients, I 2 94%). The pooled estimates for SR for those receiving anti-CD20, bruton tyrosine kinase inhibitor (BTKi), or venetoclax were 13% (95% CI 1-32%, 6 studies, 367 patients, I 2 88%), 42% (95% CI 17-71%, 3 studies, 319 patients, I 2 75%), and 20% (95% CI 0-54%, 3 studies, 39 patients, I 2 66%), respectively. The RR for those receiving treatment for their hematologic malignancy compared to those who were not receiving treatment was 0.51 (95% CI 0.37-0.71, 8 studies, 579 patients, I 2 89%;Figure 3). The RR of patients receiving anti-CD20 therapy compared to non-cancer controls was 0.13 (95% CI 0.02-0.93, 102 patients, I 2 73%). For patients treated with anti-CD20 therapy, the RR of those receiving vaccination within 9-12 months compared to beyond 9-12 months was 0.12 (95% CI 0.06-0.25, 2 studies, 74 patients, I 2 0%;Figure 4). Conclusion: Our systematic review and meta-analysis suggests that patients with hematologic malignancy have a lower SR rate following vaccination compared to controls. Furthermore, SR is variable across different types of hematologic malignancy, with very good response rates seen in patients with myeloid diseases (MPN and AML) and poor response rates seen in lymphoma and CLL. Active treatment, particu arly anti-CD20 therapy within 12 months of vaccination, is associated with a particularly low SR following vaccination. Additional studies are needed to understand non-humoral responses to vaccination, and to guide decisions regarding how to optimize vaccine response in patients with blood cancer. We plan to update the systematic review and meta-analysis as more data become available. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
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Background: Primary care physicians (PCPs) provide essential support for cancer patients. Both primary and cancer care have been affected by the COVID-19 pandemic. In the US, cancer related encounters and screening decreased over 40% and 80% respectively in January to April 2020 compared to 2019 (London et al JCO Clin Cancer Inform 2020). However, the impact of the pandemic on primary care access for cancer patients remains unclear. Methods: This was a population-based, retrospective cohort study using administrative healthcare databases held at ICES in Ontario, Canada. Patients with a new gastrointestinal (GI) malignancy diagnosed within the year prior to the pandemic, between July 1 and Sept 30, 2019 (COVID-19 cohort), were compared to patients diagnosed in years unaffected by the pandemic, between July 1 - Sept 30, 2018 and July 1 - Sept 30, 2017 (pre-pandemic cohort). Both groups were followed for 12 months after initial cancer diagnosis. In the COVID-19 cohort, this allowed for at least 4 months of follow-up data occurring during the pandemic. The primary outcome was number of in-person and telemedicine visits with a PCP. Secondary outcomes were number of in-person and telemedicine visits with a medical oncologist, number of emergency department (ED) visits, and number of unplanned hospitalizations. Outcomes, reported as number of visits per person-year, were compared between the COVID-19 and pre-pandemic cohorts. Results: 2833 individuals diagnosed with a new GI malignancy in the COVID-19 cohort were compared to 5698 individuals in the pre-pandemic cohort. The number of in-person visits to PCPs per person-year significantly decreased from 7.13 [95% CI 7.05 - 7.20] in the pre-pandemic cohort to 4.75 [4.66 - 4.83] in the COVID-19 cohort. Telemedicine visits to PCPs increased from 0.06 [0.05 - 0.07] to 2.07 [2.01 - 2.12]. Combined in-person and telemedicine visits to PCPs decreased from 7.19 [7.11 - 7.26] to 6.82 [6.71 - 6.92]. In-person visits to medical oncologists decreased from 3.73 [3.68 - 3.79] to 2.87 [2.80 - 2.94], and telemedicine visits increased from 0.10 [0.10 - 0.11] to 0.95 [0.91 - 0.99]. Combined in-person and telemedicine visits to medical oncologists remained stable (3.84 [3.78 - 3.89] vs. 3.82 [3.74 - 3.90]). The number of ED visits per person-year decreased from 1.04 [1.01 - 1.07] in the pre-pandemic cohort to 0.93 [0.89 - 0.97] in the COVID-19 cohort. Unplanned hospitalizations did not show a significant change (0.56 [0.54 - 0.58] vs. 0.53 [0.50 - 0.56]). Conclusions: PCP visits for patients with newly diagnosed GI malignancies overall decreased during the pandemic, with a dramatic shift from in-person to telemedicine visits. Visits to medical oncologists also shifted from in-person to telemedicine, but the overall combined visits remained the same. While the number of ED visits decreased, the shift in ambulatory practices did not seem to impact the number of unplanned hospitalizations.
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Introduction: Primary care physicians are essential to cancer care. They frequently identify signs and symptoms leading to a diagnosis of cancer, and provide ongoing support and management of non-cancer health conditions during cancer treatment. Both primary care and cancer care have been greatly affected by the COVID-19 pandemic. In the United States, cancer-related patient encounters and cancer screening decreased over 40% and 80% respectively in January to April 2020 compared to 2019 (London et al. JCO Clin Cancer Inform 2020). However, the impact of the COVID-19 pandemic on primary care access for cancer patients remain unclear. Methods: We undertook a population-based, retrospective cohort study using healthcare databases held at ICES in Ontario, Canada. Patients with a new lymphoid or myeloid malignancy diagnosed within the year prior to the COVID-19 pandemic, between July 1, 2019 and September 30, 2019 (COVID-19 cohort) were compared to patients diagnosed in years unaffected by the COVID-19 pandemic, between July 1, 2018 - September 30, 2018 and July 1, 2017 - September 30, 2017 (pre-pandemic cohort). Both groups were followed for 12 months after initial cancer diagnosis. In the COVID-19 cohort, this allowed for at least 4 months of follow-up data occurring during the COVID-19 pandemic. The primary outcome was number of in-person and virtual visits with a primary care physician. Secondary outcomes of interest included number of in-person and virtual visits with a hematologist, number of visits to the emergency department (ED), and number of unplanned hospitalizations. Outcomes, reported as crude rates per 1000 person-months, were compared between the COVID-19 and pre-pandemic cohorts using Poisson regression modelling. Results: We identified 2882 individuals diagnosed with a new lymphoid or myeloid malignancy during the defined COVID-19 timeframe and compared them to 5997 individuals diagnosed during the defined pre-pandemic timeframe. The crude rate of in-person primary care visits per 1000 person-months significantly decreased from 574.4 [95% CI 568.5 - 580.4] in the pre-pandemic cohort to 402.5 [395.3 - 409.7] in the COVID-19 cohort (p < 0.0001). Telemedicine visits to primary care significantly increased from 5.3 [4.8 - 5.9] to 173.0 [168.4 - 177.8] (p < 0.0001). The rate of combined in-person and telemedicine visits to primary care did not change from 579.8 [573.8 - 585.8] in the pre-pandemic cohort to 575.5 [566.9 - 584.2] in the COVID-19 cohort (p = 0.43). In-person visits to hematologists decreased from 504.1 [498.5 - 509.7] to 432.8 [425.3 - 440.3] (p < 0.0001), and telemedicine visits to hematologists increased from 6.6 [6.0 - 7.3] to 75.9 [72.8 - 79.1] (p < 0.0001). The rate of combined visits to hematologists did not change from 510.7 [505.1 - 516.4] to 508.7 [500.6 - 516.8] (p = 0.68). The rate of ED visits significantly decreased from 95.1 [92.7 - 97.6] in the pre-pandemic cohort to 84.7 [81.4 - 88.0] in the COVID-19 cohort (p < 0.0001). The rate of unplanned hospitalizations did not change from 64.8 [62.8 - 66.8] to 65.7 [62.9 - 68.7] (p = 0.60). Conclusions: Primary care visits for patients with hematologic malignancies did not significantly change during the pandemic, but there was a sizeable shift from in-person to telemedicine visits. Similar findings were seen for visits to hematologists. While the rate of visits to the ED decreased, potentially due to concern of being exposed to the COVID-19 virus, the shift in ambulatory practices did not seem to impact the rate of unplanned hospitalizations. Disclosures: No relevant conflicts of interest to declare.
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Background: Acute kidney injury (AKI) is a frequent extrapulmonary manifestation of COVID-19 and is associated with increased morbidity and mortality. We investigated alterations in the urine metabolome associated with AKI among patients with COVID-19, with the hypothesis that changes in nicotinamide adenine dinucleotide (NAD+) metabolism described in ischemic, toxic, and inflammatory AKI will be also associated with AKI in patients with COVID-19. Methods: This is a case-control study among two adult populations with COVID-19: critically ill patients hospitalized in Boston, Massachusetts, and a general hospitalized patient population in Birmingham, Alabama. Cases had AKI stages 2 or 3 by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Controls had no AKI by KDIGO criteria. Metabolites were measured by liquid chromatography -mass spectrometry. Results: 14 cases and 14 controls were included from Boston, and 8 cases and 10 controls included from Birmingham. Urinary quinolinate to tryptophan ratio, an indicator which increases with impaired NAD+ biosynthesis, was higher among cases than controls at each location and pooled across locations (median [IQR]: 1.34 [0.59-2.96] in cases, 0.31 [0.13-1.63] in controls, unadjusted p = 0.0013;p=0.03 in analyses adjusted for age and sex). We identified alterations in tryptophan, nicotinamide, and other components of energy metabolism as well as decreases in purine metabolites which contributed to a distinct urinary metabolomic signature that could reliably differentiate patients with and without AKI (supervised random forest class error: 1/14 for AKI and 1/14 for no AKI groups in Boston, 0/8 for AKI and 0/10 for no AKI groups in Birmingham). Conclusions: Conserved urinary metabolic alterations spanning multiple biochemical pathways distinguish AKI vs. non-AKI in the context of COVID-related hospitalization at two large academic medical centers. AKI is further associated with derangements in NAD+ biosynthesis that suggest impaired energy metabolism in the kidney. Augmenting renal NAD+ by administering biosynthetic precursors may present a novel therapeutic opportunity to mitigate COVID-19 associated AKI.
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Deep learning has led to major advances in fields like natural language processing, computer vision, and other Euclidean data domains. Yet, many important fields have data defined on irregular domains, requiring graphs to be explicitly modeled. One such application is drug discovery. Recently, research has found that using graph neural network (GNN) models, given enough data, can perform better than using human-engineered fingerprints or descriptors in predicting molecular properties of potential antibiotics.We explore these state-of-the-art AI models on predicting desirable molecular properties for drugs that can inhibit SARS-CoV-2. We build upon the GNN models with ideas from recent breakthroughs in geometric deep learning, inspired by the topologies of the molecules. In this poster paper, we present an overview of the drug discovery framework, drug-target interaction framework, and GNNs. Preliminary results on two COVID-19 related datasets are encouraging, achieving a ROC-AUC of 0.72 for FDA-approved chemical library screened against SARS-CoV-2 in vitro. © 2020 IEEE.
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INTRODUCTION: The objective was to investigate the changes in urology practice during coronavirus disease 2019 (COVID-19) pandemic with a perspective from our experience with severe acute respiratory syndrome (SARS) in 2003. METHODS: Institutional data from all urology centres in the Hong Kong public sector during the COVID-19 pandemic (1 Feb 2020-31 Mar 2020) and a non-COVID-19 control period (1 Feb 2019-31 Mar 2019) were acquired. An online anonymous questionnaire was used to gauge the impact of COVID-19 on resident training. The clinical output of tertiary centres was compared with data from the SARS period. RESULTS: The numbers of operating sessions, clinic attendance, cystoscopy sessions, prostate biopsy, and shockwave lithotripsy sessions were reduced by 40.5%, 28.5%, 49.6%, 44.8%, and 38.5%, respectively, across all the centres reviewed. The mean numbers of operating sessions before and during the COVID-19 pandemic were 85.1±30.3 and 50.6±25.7, respectively (P=0.005). All centres gave priority to cancer-related surgeries. Benign prostatic hyperplasia-related surgery (39.1%) and ureteric stone surgery (25.5%) were the most commonly delayed surgeries. The degree of reduction in urology services was less than that during SARS (47.2%, 55.3%, and 70.5% for operating sessions, cystoscopy, and biopsy, respectively). The mean numbers of operations performed by residents before and during the COVID-19 pandemic were 75.4±48.0 and 34.9±17.2, respectively (P=0.002). CONCLUSION: A comprehensive review of urology practice during the COVID-19 pandemic revealed changes in every aspect of practice.