ABSTRACT
COVID-19 infection continues to be a health threat particularly to immunocompromised transplant recipients. These patients remain at high risk for the development of severe disease. So, it was imperative to study the humoral response to COVID-19 vaccines in these patient to learn and to establish protocols or policies for the prevention and treatment of their infection. We evaluated 90 sera from 36 heart and 34 from kidney transplant recipients for antibodies to COVID-19 (SARS-COV-2) following first, second or third vaccination. Antibodies were measured by 2 commercial methods of rapid test for qualitative detection of IgM and IgG or by single antigen beads. The latter was for semi-quantitative detection of IgG to RBD (receptor binding protein), S (Spike protein), S1 motif (receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2) and S2 motif (mediates viral RNA to cell membrane fusion) of spike protein. Our finding demonstrates that almost half of the patients had no detectable antibodies by either of the methods. The single antigen beads assay was a better method in detecting antibodies with less false negative as compared to the rapid method. In patients who had developed antibodies to COVID-19, level of antibodies measured by MFI values increased after 2nd and 3rd dose of vaccinations. Of 18 patients who received the 3rd vaccine (first boost), 7 remained to have no detectable antibodies, 5 seroconverted to be positive and the other 6 demonstrated increase in their antibody levels. Interestingly, the titer of antibodies to S2 was lower than RBD, S and S1 and diminished more rapidly. In addition, patients who had both Covid-19 infection and vaccinations had higher level of antibodies to all, including the S2 motif. Furthermore, our data showed that patients with longer transplants demonstrated better humoral response to vaccines. COVID-19 vaccination in immunocompromised solid organ transplant recipients have resulted in detectable antibody response in almost half of the patients which is expected to be protective and prevent severe complications. Our observation supports the need to develop policies for mandatory vaccination prior to transplant as 39% of immunocompromised solid organ transplants had no detectable antibodies even after 3 doses of vaccine. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Purpose: The diverse factors affecting the vaccine induced neutralizing antibody response in solid organ transplant recipients and their immunity against CoV2 variants are needed to be well characterize to understand how we improve the vaccine efficacy. Method(s): Anti-CoV2 receptor binding domain (RBD) plasma antibody response and their neutralization potency in 29 kidney and 22 heart transplant patients was determined with recombinant RBD protein binding ELISA and by calculating the 50% virus neutralization titer of the plasma antibody with ACE2-Hu-HeLa cell based pseudo virus neutralization assay against CoV2 wild type and delta variant. Result(s): We detected strong binding and protective neutralizing plasma antibody response in SOTR who were infected with CoV-2 either prior to or after the first dose of vaccine (n=8), who showed high median IC50 value > 10,000 against both the CoV2 wild type strain and the more transmissible delta variant. In contrast to this, the CoV2 uninfected and vaccinated SOTR ( naive vaccinees, n=43) had considerably lower anti-RBD plasma antibody binding titers, and only 19% of this population possessed minimally protective neutralizing antibody titer (IC50 >50) against the wild type CoV2 strain, which further decreased to 10% against the delta variant. While IgG and IgA were dominant isotypes of anti-RBD antibody induced by the CoV2 vaccines and correlated significantly (r=0.84, p=<0.001) with the CoV2 neutralization. The COV2 uninfected SOTR vaccinees who were within 1.5 years from transplantation or African American ethnicity were less likely to have detectable vaccine induced neutralizing antibody responses than the other populations. In the naive vaccinees, administration of corticosteroids in combination with calcineurin or mTOR inhibitors and antimetabolites also negatively affected the CoV2 antibody responses, while female and younger organ transplant recipients tended towards higher IgM and IgA titers. Kidney transplant recipients showed better IgG responses vs heart transplant recipients and elevated serum creatinine levels correlated with poorer antibody response to the vaccines in both kidney and heart transplant groups. Conclusion(s): These results suggest that in the absence of immunity due to CoV2 infection, vaccination in SOTRs induces much lower protective antibody levels than in healthy controls and identifies African-American ethnicity, less than 1.5 years post transplantation as additional risk factors that further exacerbate these effects. Poor kidney function negatively affected the vaccine induced antibody response.
ABSTRACT
ASSISTments is a free online learning tool for improving students’ mathematics achievement by providing immediate feedback and hints to students, detailed information on how students performed to teachers, and instructional suggestions for teachers to use. Researchers at the Friday Institute for Educational Innovation conducted an intrinsic, longitudinal multiple-case study of 7th-grade mathematics teachers’ implementation of ASSISTments and its impact on their instruction before and during the COVID-19 pandemic. The study examined teachers’ use of ASSISTments in three instructional contexts: in- person only, remote only, and both in-person and remote. Our findings indicate that teachers in all contexts changed their instructional practices for homework review and for determining whether their students had understood lessons. Teachers used the ASSISTments auto-generated reports to focus their homework reviews, based on their students’ performance, and to provide instructional interventions and/or re-teaching. They also used the instructional suggestions provided by the ASSISTments platform to plan lessons to re-teach concepts or to review prior instruction with their students. © 2022, Springer Nature Switzerland AG.
ABSTRACT
RATIONALE: Around 4.6 million people in the United Kingdom (UK) have asthma, with an estimated 5.7% treated for severe asthma. Benralizumab is indicated for the treatment of severe eosinophilic asthma (SEA) in adults inadequately controlled despite appropriate maintenance therapy. The Connect 360 Patient Support Programme (PSP) for patients on benralizumab includes options for home-based drug administration, education and adherence support by trained nurses - of particular relevance during the COVID-19 pandemic. Limited evidence exists on the benefit of PSPs for asthma patients or those administering biological therapies at home. This study aims to describe patient characteristics, key outcomes and experience with the PSP using UK data from Connect 360. METHODS: A non-interventional, retrospective cohort study of patients, enrolled in the PSP (Oct-2019 onwards) and consenting to the use of personal data for research purposes (“study cohort”). Patients opting for additional support services with at least one nurse interaction within described study timeframes formed the clinical cohort. Patients were observed up to 48 weeks post-PSP enrolment (interim data taken on 31-Mar-2021;data collection ongoing) with study endpoints assessed at baseline (0-4 weeks), 24 (±4) weeks and 48 (±8) weeks post-PSP enrolment. Characteristics at enrolment are described for the study cohort. Patient-reported clinical outcomes (hospitalisations, maintenance oral corticosteroid [mOCS] use, Asthma Control Questionnaire [ACQ-6] scores) and service satisfaction (1-5 point scale, 5 being most satisfied) were analysed where available from routine PSP nurse calls/visits. Analysis was descriptive;Kaplan-Meier estimators were used to estimate PSP discontinuation rates. RESULTS: The study cohort was 611 patients (mean enrolment age: 54.1 years, 63.2% female [N=323]). Most (98.9%) were benralizumab users on maintenance dosing (8-weekly) at enrolment. The clinical cohort consisted of 149 (baseline), 175 (24 weeks) and 195 (48 weeks) patients. PSP discontinuation rates were 4.4% and 11.6% at 24 and 48 weeks. Proportion of patients reporting mOCS use was 49.7%, 44.0% and 32.8% at each timepoint and hospitalizations were 10.9% and 4.1% at 24 and 48 weeks. Mean ACQ-6 scores decreased over time. Mean (SD) satisfaction scores were 4.6 (0.7) and 4.8 (0.5) at 24 and 48 weeks, respectively. (Table 1). CONCLUSIONS: Overall patients' experience with the PSP was positive, evidenced by high satisfaction with and persistence to the PSP. Where data were available, proportion of patients reporting mOCS and hospitalizations at 48 weeks were numerically lower than previous timepoints and mean ACQ-6 scores improved, suggesting a positive impact of benralizumab treatment within the PSP.
ABSTRACT
Purpose: The COVID-19 pandemic has disrupted many facets of life for rural and urban patients with cancer. Here, we characterize the impact of the pandemic on social and health behaviors of rural and urban cancer patients. Methods: N=1,326 adult cancer patients, who visited HCI in the last 4 years and enrolled in either Total Cancer Care or Precision Exercise Prescription studies, completed a COVID-19 survey. The survey was administered between Aug and Sept 2020 and included questions on demographic and clinical information as well as employment status, health behaviors, and COVID-19 prevention measures. Results: The mean age was 61 (19-92) years, with 54% female, 97% non-Hispanic White, 80% stage I-III, 42% employed full or part-time, 25% living in rural counties, and 85% reporting good to excellent overall health. Cancer patients in rural compared to urban counties were more likely to be older (rural=63 vs. urban=60 years;p=0.01), retired or not employed (rural=63% vs. urban=56%;p=0.04), not have health insurance coverage (rural=4% vs. urban=2%;p=0.01), and have ever smoked (rural=35% vs. urban=24%;p=0.001). However, urban patients reported “somewhat” to “a lot” of change in their daily lives more frequently than rural patients (urban=86% vs. rural=77%;p<0.001), but there were no differences in change in social interaction or feeling lonely between populations. Changes in health behaviors namely exercise habits due to the pandemic were more common in patients residing in urban vs. rural counties (urban=51% vs. rural=39%;p<0.001), with more urban patients either exercising less (urban=23% vs. rural=17%) or more frequently (urban=12% vs. rural=8%);however, there were no significant differences with respect to changes in alcohol consumption between these groups. In terms of prevention measures, urban patients compared to rural patients were more likely to use face masks “fairly” or “very often” (urban=94% vs. rural=83%;p<0.001) and also felt they were more likely to contract a COVID-19 infection (22% vs. 14%;p=0.003), but there were no differences for other risk mitigation behaviors, such as hand sanitizer use. Conclusion: These findings suggest that the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties. Rural patients were more likely to have risk factors associated with poor health outcomes, such as not having health insurance coverage and having a history of smoking. However, urban patients were more likely to experience larger changes in their daily lives and exercise habits. Urban patients were more likely to follow preventive measures (e.g., wearing face masks) and felt they were at a greater risk of contracting the virus. Further research is needed to better characterize the pandemic's short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions.
ABSTRACT
The COVID-19 pandemic has illustrated the global demand for rapid, low-cost, widely distributable and point-of-care nucleic acid diagnostic technologies. Such technologies could help disrupt transmission, sustain economies and preserve health and lives during widespread infection. In contrast, conventional nucleic acid diagnostic procedures require trained personnel, complex laboratories, expensive equipment, and protracted processing times. In this work, lyophilized cell-free protein synthesis (CFPS) and toehold switch riboregulators are employed to develop a promising paper-based nucleic acid diagnostic platform activated simply by the addition of saliva. First, to facilitate distribution and deployment, an economical paper support matrix is identified and a mass-producible test cassette designed with integral saliva sample receptacles. Next, CFPS is optimized in the presence of saliva using murine RNase inhibitor. Finally, original toehold switch riboregulators are engineered to express the bioluminescent reporter NanoLuc in response to SARS-CoV-2 RNA sequences present in saliva samples. The biosensor generates a visible signal in as few as seven minutes following administration of 15 µL saliva enriched with high concentrations of SARS-CoV-2 RNA sequences. The estimated cost of this test is less than 0.50 USD, which could make this platform readily accessible to both the developed and developing world. While additional research is needed to decrease the limit of detection, this work represents important progress toward developing a diagnostic technology that is rapid, low-cost, distributable and deployable at the point-of-care by a layperson.
Subject(s)
Biosensing Techniques , COVID-19 , Luminescent Measurements , RNA, Viral/isolation & purification , Saliva/chemistry , COVID-19/diagnosis , Humans , Luciferases , SARS-CoV-2ABSTRACT
Purpose: The COVID-19 pandemic has substantially changed social practices, economic stability, and access to medical care that may significantly affect cancer patients, especially those undergoing active treatment. We characterized the pandemic's influence on healthcare delivery, behavioral health, and financial stress in cancer patients. Methods: We included data from N = 1,253 adult cancer patients, who visitedHCI in the last 4 years, consented to the Total Cancer Care study, and completed a COVID-19 survey as part of the COPES consortium. The survey was administered between Aug and Sept 2020 and included questions on change/cancellation of medical visits, change in exercise and alcohol consumption, daily life, social interactions, and financial stress sinceMarch 2020. Results:The cohort'smean agewas 60.4 (19-92) years, with 54% female, 68% non-Hispanic White, 41% retired, 43% employed full or part-time, and 24% living in rural counties.Among the 27% of patients who reported receiving current treatment at HCI, 30% had to change or cancel a medical visit due to the pandemic, with 2% reported a change/cancellation in a biopsy, surgery, radiotherapy, and chemotherapy;5% reported a change/cancellation in imaging;and 3% and 23%reported a change/cancellation in cancer screening and doctor's visit, respectively. 18% rescheduled an appointment to a telehealth visit. Changes in exercise habits due to the pandemic were common (47%), with 10% no longer exercising regularly, 21% exercising less, and 11% exercising more than before. 5% reported increased alcohol consumption, while 6% reported a decrease. Most patients (84%) experienced a change in their daily lives (ranging from somewhat to a lot of change). 69% had fewer social interactions, and 49% reported financial stress due to the pandemic, with 11% reporting being quite a bit/very much financially stressed. Conclusions: These findings suggest that within approximately the first 6 months, the COVID-19 pandemic had a substantial impact on cancer patients' lives, with adverse effects on health behaviors and financial stress. Healthcare delivery continued for essential cancer care but was disrupted for other services, such as cancer screening. Further analyses are underway.
ABSTRACT
The novel coronavirus, designated by the World Health Organization as COVID-19 has required many countries around the world to close work spaces, schools and public venues. This has required policy makers and venue managers to investigate practical mitigation strategies using technology to exit the lockdown safely and enable the reopening of public spaces. This paper introduces Digital personal protective equipment (PPE), a dynamic and affordable wearable approach that remind people to keep their distance and keep track of their contact traces. This IoT based BLE probing technique approach empowers employers, city and venue managers to encourage social-distancing and trigger a friendly alert using vibration when social distancing is violated in privacy-preserving manner. © 2020 Owner/Author.