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1.
Medicine Today ; 22(4):43-46, 2021.
Article in English | Scopus | ID: covidwho-2011566

ABSTRACT

Coronavirus disease 2019 (COVID-19) is known to result in gastrointestinal symptoms and liver damage. Consideration needs to be given to COVID-19 as a potential cause of new-onset gastrointestinal symptoms. Awareness of special issues affecting patients with chronic gastrointestinal and liver diseases in a pandemic is important. © 2021 Medicine Today Pty Ltd. All rights reserved.

2.
Cytotherapy ; 24(5):S147, 2022.
Article in English | EMBASE | ID: covidwho-1996729

ABSTRACT

Background & Aim: Blood is one of the most vital resources in modern medicine. Blood transfusions have become an essential and often lifesaving procedure for accidents, during surgery, for patients with chronic disorders such as anemia, sickle cell disease, cancer, and myriad other circumstances. However, despite the rapidly growing world population, the availability of healthy blood donors is declining with aging populations. Furthermore, natural and man- made calamities often produce sudden and concentrated shocks in demand, which strains global supply chains. The COVID-19 pandemic has demonstrated this issue on a global scale by reducing the number of blood drives and donations, resulting in 39% of blood centers in the United States being left with only one- to two-day supplies, and a 50% drop of blood units collected in countries such as Zambia. Additionally, storage limitations of 42 days for donor blood limits stock availability during peak demand. Large-scale generation of universal red blood cells (RBCs) from O-ve human induced pluripotent stem cells (hiPSCs) offers the potential to alleviate blood shortages and provide a secure year-round supply. Mature iPSC-derived RBCs and reticulocytes could also find important applications in research in malaria and COVID-19 studies. (Figure Presented) Fig. 1 ( 700). Methods, Results & Conclusion: In this study, we have reprogrammed hiPSC from CD34+ O-ve cells and demonstrated the smallscale generation of high-density cultures of erythroblasts in a stirred perfusion bioreactor system. Twenty O-ve iPSC lines were derived, screened, and characterized for their ability to differentiate towards the erythroid lineage, showing high expression of mesoderm (KDR+, 64.9%), hematopoietic (CD34+/CD45+, 68.4%;CD34+/CD43+, 84.9%), and erythroid markers (CD235a+, 83,5%), and were able to undergo enucleation in vitro. Using the best clones, we were able to achieve erythroblast peak cell density of 34.7 million cells/mL with 92.2% viability in an Applikon perfusion bioreactor using an ultrasound system (Sonosep) to concentrate cells while removing waste media. This resulted in a cumulative-fold expansion of over 1,500 after 29 days of culture. Cells carried O2 effectively as demonstrated by hemoglobin dissociation curves. The perfusion culture platform paves the way for controlled high-density bioreactor culture for the generation of RBCs.

3.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927799

ABSTRACT

Organoids are emerging to be an excellent tool for studying human development and disease. The COVID-19 pandemic has highlighted the importance of physiologically relevant alveolar infection models that include both alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. To address the need for an alveolar organoid culture system for respiratory research, we developed the PneumaCult™ Alveolar Organoid Expansion and Differentiation Media for the highly efficient expansion of isolated primary human AT2 cells and subsequent differentiation into AT1 cells. Alveolar organoids were established from a panel of various donors (n=5) by culturing purified human AT2 cells in Corning® Matrigel® domes with serum-free PneumaCult™ Alveolar Organoid Expansion Medium. Typically by day 10-14 the organoids are fully established and display a spherical morphology. Alveolar organoids can then be either expanded long-term by passaging cultures as single cells in Expansion Medium or differentiated into AT1 cells using the PneumaCult™ Alveolar Organoid Differentiation Medium. Organoids in PneumaCult™ Alveolar Organoid Expansion Medium contain self-renewing AT2 cells marked by the expression of HT2-280 in 89.9 +/- 14.5 (mean +/- SD;n=5 donors) of cells and the presence of Pro-SPC, demonstrate a great expansion potential of > 10,000-fold with more than 13 population doublings within 10 passages (n=5 donors). Alveolar organoids differentiated for 10 days in the PneumaCult™ Alveolar Organoid Differentiation Medium downregulate AT2 markers HT2-280 and Pro-SPC and start expressing AT1 markers HT1-56 in 93.8 +/- 7.2 (mean +/- SD;n=5 donors) of cells and are positive for RAGE and GPRC5a. Furthermore, we assessed the expression of SARS-CoV-2 entry receptor ACE2, which is present in both undifferentiated and differentiated alveolar organoids.To investigate the use of these alveolar organoids for infectious disease modeling, AT2-containing alveolar organoids were transduced with a GFP-labelled Respiratory Syncytial Virus (RSV). Alveolar organoids were susceptible to viral infection and replication was confirmed by fluorescence microscopy and quantitative PCR. In summary, the PneumaCult™ Alveolar Organoid Expansion and Differentiation Media are highly efficient and reproducible tools for the feeder-free expansion of AT2 cells and robust differentiation into AT1 cells, which can be used for infectious disease modeling.

4.
Epidemiology ; 70(SUPPL 1):S260-S261, 2022.
Article in English | EMBASE | ID: covidwho-1853993

ABSTRACT

Background During COVID-19, social distancing was prevalent to curb disease transmission, particularly for vulnerable older adults. However, this isolation leads to low mood, functional decline and frailty. Hence, such preventative measures have brought to the fore the heavy implications of social isolation, the lack of social contact and interaction. Associated but separate is loneliness, the feeling of being alone or separated from others. While it is evident that either or both impact health negatively, attributable risk factors and relationship with geriatric syndromes such as frailty and sarcopenia are still unclear. Understanding these aspects would be important in developing healthcare policies to reduce social isolation and loneliness in our older adults. Hence, we aim to investigate the differential determinants of social isolation and loneliness in community dwelling older adults. Methods We surveyed 299 community dwelling older adults ≥60years. Parameters documented include demographics, 6-item Lubben Social Network Scale, UCLA loneliness scale, EQ5D, Montreal Cognitive Assessment, Geriatric Depression Scale, functional screening with Barthel index, Lawton instrumental activities of daily living scale, FRAIL scale and SARC-F. Linear regression analysis was performed. Results 234(78.26%) were female, mostly of Chinese ethnicity(90.30%), mean age 74.31±7.81years. 62(20.74%) were living alone. 220(73.58%) had primary school education or less. Mean number of chronic diseases 1.57±0.07 and 81(27.09%) classified as frail, ie FRAIL score 3 and above. Social isolation was significantly correlated with perceived health status (β=0.08;95%CI 0.04 to 0.13;p<0.01), self-care (β= -2.18;95%CI -4.19 to -0.17;p=0.03), sarcopenia (β= -0.57;95%CI -1.12 to -0.02;p=0.04) and cognition (β=0.26;95% CI 0.12 to 0.39;p<0.01). Loneliness was significantly correlated with pain (β= -0.23;95%CI -0.45 to -0.01;p=0.04). Conclusion Social isolation was linked to lower perceived health and cognition, but better physical function as seen from lower levels of sarcopenia and issues with self-care. This finding highlights that isolated older adults may not only be limited by physical disabilities. Mood and cognition have to be considered. Loneliness on the other hand was linked to pain, emphasising that this common symptom has far-reaching implications. Our study is important in identifying key risk factors to be investigated. More work is needed to delineate mechanisms.

5.
Open Forum Infectious Diseases ; 8(SUPPL 1):S17-S18, 2021.
Article in English | EMBASE | ID: covidwho-1746814

ABSTRACT

Background. Allogeneic stem cell transplant (SCT) recipients are at an increased risk of poor outcomes from COVID-19. While the mRNA-1273 (Moderna) and BNT162b2 (Pfizer) COVID-19 mRNA vaccines are highly immunogenic in the general population, the immune response in SCT recipients is poorly understood. We characterized the immunogenicity and reactogenicity of COVID-19 mRNA vaccines in a cohort of SCT patients. Methods. We performed a prospective cohort study of 16 allogeneic SCT patients and 23 healthy controls. Blood samples for both cohorts were collected prior to first vaccination (baseline), at the time of second vaccination, and approximately 28 days post-second vaccination. Anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG levels were measured quantitatively from plasma using a multiplexed single molecule array (Simoa) immunoassay. Reactogenicity was captured for the SCT cohort via a self-reported post-vaccination diary for 7 days after each dose. Results. Demographics and SCT recipients' characteristics are shown in Table 1. In the SCT cohort, we observed a significantly lower anti-S (p< 0.0001), S1 (p< 0.0001), and RBD (p< 0.0001) IgG responses as compared to healthy controls, both at the time of dose 2 and 28 days post-vaccine series (Fig 1). Overall, 62.5% of SCT recipients were responders after vaccine series completion, as compared to 100% of healthy controls (Fig 2). While no patients had a reported history of COVID-19 diagnosis, 2 patients in the SCT cohort had elevated anti-S IgG levels and 1 showed elevated anti-N at baseline. 10/16 participants in the SCT cohort completed at least one post-vaccination diary. Local and systemic reactions were reported by 67% and 22% of participants, respectively, after dose 1, and 63% and 50% after dose 2 (Figure 3). All reported events were mild. Anti-Spike (A), anti-S1 (B), anti-RBD (C), and anti-nucleocapsid (D) IgG titers were measured at baseline, time of second dose, and approximately 28 days after second vaccination. IgG levels were measured quantitatively using multiplexed single molecule array (Simoa) immunoassays, and are reported as Normalized Average Enzymes per Bead (AEB). Allogeneic stem cell transplant recipients (mauve) showed significantly lower anti-S, S1, and RBD IgG responses as compared to healthy controls (mint). Low titers of anti-N IgG demonstrates no history of COVID-19 natural infection during the course of the study. 10 allogeneic stem cell transplant recipients completed at least one diary for 7 days after vaccination. Reactions after dose 1 are shown in light blue, and reactions after dose 2 are shown in dark blue. Local reactions (A) were reported by 67% (6/9) of participants after dose 1, and 63% (5/8) after dose 2. Systemic reactions (B) were reported by 22% (2/9) of participants after dose 1, and 50% (4/8) after dose 2. All reported events were mild (Grade 1). Conclusion. Among SCT recipients, mRNA COVID-19 vaccines were well-tolerated but less immunogenic than in healthy controls. Further study is warranted to better understand heterogeneous characteristics that may affect the immune response in order to optimize COVID-19 vaccination strategies for SCT recipients. Figure 2: Response Rate to COVID-19 Vaccination An internally validated threshold for responders was established using pre-pandemic sera from healthy adults. A positive antibody response was was defined as individuals with anti-Spike IgG levels above the 1.07 Normalized AEB threshold.

6.
Anesthesia and Analgesia ; 133(3 SUPPL 2):874-875, 2021.
Article in English | EMBASE | ID: covidwho-1444950

ABSTRACT

High-fidelity simulation training in CPR (CPR-HFST) could identify weaknesses in pre-COVID-19 Code Blue (CB) practices. Importantly, PPE donning may delay CPR thus worsening patient outcomes. We sought to determine the effect of our CPR-HFST on clinical practice. A retrospective review of CB events in a 1000-bedded hospital, pre- and intra-pandemic was conducted from 01/05/2019 to 30/10/2020. Onset of the pandemic was taken as 04/02/2020. CPR-HFST commenced in January 2020. The primary objective was to determine pre- and intra-pandemic response times. Intubation times, patient outcomes (quantified by CB survival rates and the CPC score), and incidence of HCW infection were our secondary objectives. The CCI score was used to stratify patients with similar comorbidities. Two-tailed Chi-square and Mann-Whitney tests were used for statistical comparisons, alpha = 0.05. 158 CB events were reviewed. Median response time was longer intra-pandemic compared to prepandemic;4.0 mins (IQR: 3-5) vs. 3.0 mins (IQR:1-4), p=0.0007. Cardiac rhythms were asystole (25.5%), PEA (53.8%), VT (5.7%), and VF (11.3%). 67.1% of patients required CPR, of which, 88.7% were intubated. There were no significant differences in median intubation times: 12.0 (prepandemic) vs. 11.0 mins (intra-pandemic), p=0.89. Survival to hospital discharge were similar;14.1% (pre-pandemic) vs. 21.4% (intra-pandemic), p=0.33. We did not find any significant differences in survival rates and CPC scores (Table 1). There were no HCW infections. Survival to hospital discharge rates of patients requiring in-hospital CPR may be lower intrapandemic;Miles et al reported 3.2% vs 12.8% respectively, p<0.01. These were significantly different compared to our intra-pandemic cohort (3.2% vs. 21.4%, p<0.01) but not in our pre-pandemic cohort (12.8% vs. 14.1%, p=0.82). Reasons for the differences are likely multifactorial. Nonetheless, in our experience and data, we believe CPR-HFST prevents deterioration in the standards of care and may help in optimising CPR outcomes. (Table Presented) .

7.
Blood ; 136:4-5, 2020.
Article in English | EMBASE | ID: covidwho-1344058

ABSTRACT

Characterization of molecular alterations in acute myeloid leukemia (AML) has led to development of targeted therapies, including FLT3 and IDH1/2 inhibitors. Maintenance therapy following hematopoietic cell transplantation (HCT) has shown substantial promise. Enasidenib (ENA), a selective IDH2 inhibitor, was associated with impressive rates of response in relapsed/refractory (R/R) AML and is now FDA-approved for this indication. We sought to assess the tolerability and define the maximum tolerated dose (MTD) of ENA as maintenance following HCT for IDH2-mutated myeloid malignancy. HCT-eligible patients (pts) ≥ 18 years with AML in remission, or myelodysplastic syndrome (MDS) with <5% marrow blasts, were enrolled. There were no restrictions on conditioning or donor type. A 2-step registration process was utilized;1 before HCT and 1 before ENA initiation. Before HCT, pts were required to have normal organ and recovered marrow function (neutrophils > 1000/µL and platelets > 50000/µL). Those with prior HCT, active disease, QTc ≥450ms, and active infections were excluded. ENA was initiated between day 30 and 90 after HCT, at which time the following were required: chimerism ≥70% of donor origin among blood/marrow cells, no acute graft versus host disease (aGVHD) requiring ≥0.5mg/kg/day prednisone or equivalent, and no relapse. ENA was taken orally (po) daily (qd) in 28-day cycles. The period for dose-limiting toxicity (DLT) evaluation was the first cycle, escalation to successive levels was guided by DLT incidence, and 2 levels (50mg,100mg) were studied. Following establishment of MTD or recommended phase 2 dose (RP2D), 10 pts would be enrolled in an expansion cohort. Pts were monitored for relapse and toxicity and continued until disease progression, intolerable toxicity, or receipt of 12 cycles. Nineteen pts have been registered prior to HCT at 3 sites, Massachusetts General Hospital, Dana Farber Cancer Institute, and Johns Hopkins Hospital. Three pts could not initiate ENA following HCT;2 due to logistic challenges of the COVID pandemic and 1 due to relapse. The remaining 16 pts initiated ENA treatment. The median age was 61 years (range 31-76);12 (75%) were male, and 13 (81%) were Caucasian. Fourteen (88%) had AML, of which 6 were AML with MDS related changes and 2 had antecedent myeloproliferative neoplasm. Two pts (13%) had MDS. Among these 16 pts, 9 (56%) had IDH2 R140, and 5 (25%) had IDH2 R172 mutations. IDH2 subtype data was unavailable for 2 pts. Of 15 pts with available data from time of diagnosis, 11 (73%) had intermediate-risk and 4 (27%) had adverse-risk cytogenetics. Among these 15 pts, common concurrent mutations were DNMT3A (47%), SRSF2 (33%), and RUNX1 (33%). Eleven AML pts (85%) received intensive versus non-intensive therapies (15%) prior to HCT, and among all pts, 7 (44%) had received ENA prior to HCT. HCT data was available for all 16 pts;4 pts (25%) received myeloablative, and 12 (75%) received reduced-intensity conditioning. Nine pts (56%) had a matched unrelated, 6 (38%) had haploidentical, and 1 (6%) had a matched related donor HCT. Three pts were enrolled at the 50mg dose level, 6 pts at 100mg, and after no DLTs were detected, the remaining were enrolled in an expansion cohort at 100mg qd. Median follow-up (F/U) for surviving patients is currently 11.7 months (range 1.5-18.9). 2 pts (13%) have relapsed during F/U, at 96 and 364 days post HCT. Additional ≥grade (G) 3 toxicities detected during treatment, possibly or probably related to ENA, included neutropenia, anemia, and bilirubinemia. Six pts (38%) required dose interruptions lasting a median 19 days (range 7-25), 4 required a dose reduction to 50mg, and 1 stopped treatment due to G3 bilirubinemia. In total, 3 pts (18%) discontinued study treatment, 1 for aforementioned G3 bilirubinemia, 1 to pursue a GVHD trial, and 1 for relapse. Six pts have completed the 12-month f/u without relapse, and 7 remain on study. 15 of 16 pts remain alive. Thus far, 3 pts have experienced ≥ G2 aGVHD, and 4 had moderate chronic GVHD. Serial me surement of 2HG is being conducted on samples, and these will be reported. Enasidenib is well-tolerated as post-HCT maintenance therapy for myeloid malignancy at the RP2D of 100mg qd. No DLTs have been detected, and a low rate of post-HCT relapse has been identified to date, although longer f/u is needed. Larger, randomized studies of ENA in the post-SCT setting would determine the true efficacy of this agent as maintenance therapy. Disclosures: Fathi: Blueprint: Consultancy;Jazz: Consultancy;Amgen: Consultancy;Newlink Genetics: Consultancy;Pfizer: Consultancy;Abbvie: Consultancy;Seattle Genetics: Consultancy, Research Funding;Agios: Consultancy, Research Funding;PTC Therapeutics: Consultancy;Takeda: Consultancy, Research Funding;Boston Biomedical: Consultancy;Amphivena: Consultancy;BMS/Celgene: Consultancy, Research Funding;Kite: Consultancy;Trovagene: Consultancy;Forty Seven: Consultancy;Novartis: Consultancy;Daiichi Sankyo: Consultancy;Astellas: Consultancy;Trillium: Consultancy;Kura Oncology: Consultancy. Soiffer: Gilead: Consultancy;Novartis: Consultancy;Juno: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;VOR Biopharma: Consultancy;alexion: Consultancy;Rheos Therapeutics: Consultancy;Cugene: Consultancy;Precision Bioscience: Consultancy;Be the Match/ National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees;Kiadis: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Consultancy. Levis: Menarini: Honoraria;Amgen: Honoraria;FujiFilm: Honoraria, Research Funding;Astellas: Honoraria, Research Funding;Daiichi-Sankyo: Honoraria. Mims: Novartis: Speakers Bureau;Kura Oncology: Membership on an entity's Board of Directors or advisory committees;Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study;Agios: Consultancy;Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees;Jazz Pharmaceuticals: Other: Data Safety Monitoring Board;Abbvie: Membership on an entity's Board of Directors or advisory committees. Devine: Magenta Therapeutics: Consultancy. Defilipp: Incyte: Research Funding;Regimmune: Research Funding;Syndax Pharmaceuticals: Consultancy. Spitzer: Jazz Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees;Bluebird Bio: Membership on an entity's Board of Directors or advisory committees. Frigault: Celgene: Consultancy;Arcellx: Consultancy;Novartis: Consultancy, Research Funding;Gilead/Kite: Consultancy, Research Funding. Amrein: Amgen: Research Funding;AstraZeneca: Consultancy, Research Funding;Takeda: Research Funding. Hobbs: Incyte: Research Funding;Merck: Research Funding;Bayer: Research Funding;Constellation: Honoraria, Research Funding;Jazz: Honoraria;Celgene/BMS: Honoraria;Novartis: Honoraria. Brunner: Janssen: Research Funding;Acceleron Pharma Inc.: Consultancy;GSK: Research Funding;Xcenda: Consultancy;Takeda: Consultancy, Research Funding;Novartis: Consultancy, Research Funding;Jazz Pharma: Consultancy;Forty Seven, Inc: Consultancy;Celgene/BMS: Consultancy, Research Funding;Biogen: Consultancy;Astra Zeneca: Research Funding. Narayan: Genentech: Other: Prior Spouse employment within 24 months and prior spouse equity divested within past 24 months;Takeda: Other: Prior Spouse employment within 24 months;Sanofi-Genzyme: Other: Current Spouse employment. Chen: AbbVie: Other: Data and Safety Monitoring Board Member;Incyte Corporation: Consultancy;Takeda: Consultancy;Actinium: Other: Data and Safety Monitoring Board Member;Equillium: Other: Data and Safety Monitoring Board Member;Magenta: Consultancy;Kiadis: Consultancy. OffLabel Disclosure: Enasidenib as post-transplant maintenance therapy

8.
Sexually Transmitted Infections ; 97(Suppl 1):A22-A23, 2021.
Article in English | ProQuest Central | ID: covidwho-1301677

ABSTRACT

BackgroundWe evaluated the impact of the Coronavirus Disease (COVID-19) on the sex work industry, and assessed how it has impacted the health and social conditions of sex workers in Singapore.MethodsWe conducted a sequential exploratory mixed methods study amidst the COVID-19 pandemic from April to October 2020, including in-depth interviews with 24 stakeholders from the sex work industry and surveyor-administered structured surveys in the field with 171 sex workers. The in-depth interviews allowed the team to qualitatively explore and generate themes around how COVID-19 had impacted sex workers in Singapore, and informed the design of the quantitative surveyor-administered survey questionnaire. Qualitative data were analyzed through framework analysis while survey data were analyzed through descriptive statistics, and multivariable Poisson regression models.ResultsCOVID-19 had a substantial impact on sex workers’ income, while the illegality of sex work, stigma, and the lack of work documentation were cited as exclusionary factors for access to alternative jobs or government relief. Sex workers had experienced an increase in food insecurity (57.3%), housing insecurity (32.8%), and sexual violence and compromise (8.2%), as well as a decrease in access to medical services (16.4%). Being transgender female was positively associated with increased food insecurity (aPR=1.23, 95%CI [1.08, 1.41]), housing insecurity (aPR=1.28, 95%CI [1.03, 1.60]) and decreased access to medical services (aPR=1.74, 95%CI [1.23, 2.46]), being a venue-based sex worker was positively associated with increased food insecurity (aPR=1.46, 95%CI [1.00, 2.13]), and being a non-Singaporean citizen or permanent resident was positively associated with increased housing insecurity (aPR=2.59, 95%CI [1.73, 3.85]).ConclusionsOur findings suggest that COVID-19 has led to a loss of income for sex workers, leading to a worsening of social and health conditions for sex workers. A lack of access to government relief among sex workers exacerbated such conditions.

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