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1.
Viruses ; 14(7)2022 06 24.
Article in English | MEDLINE | ID: covidwho-1911652

ABSTRACT

Antigenic imprinting, which describes the bias of the antibody response due to previous immune history, can influence vaccine effectiveness. While this phenomenon has been reported for viruses such as influenza, there is little understanding of how prior immune history affects the antibody response to SARS-CoV-2. This study provides evidence for antigenic imprinting through immunization with two Sarbecoviruses, the subgenus that includes SARS-CoV-2. Mice were immunized subsequently with two antigenically distinct Sarbecovirus strains, namely SARS-CoV-1 and SARS-CoV-2. We found that sequential heterologous immunization induced cross-reactive binding antibodies for both viruses and delayed the emergence of neutralizing antibody responses against the booster strain. Our results provide fundamental knowledge about the immune response to Sarbecovirus and important insights into the development of pan-sarbecovirus vaccines and guiding therapeutic interventions.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Animals , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , Immunization , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
2.
Aesthet Surg J ; 2022 Jun 16.
Article in English | MEDLINE | ID: covidwho-1901113

ABSTRACT

BACKGROUND: CBL-514 is a novel injectable drug that may be safe and efficacious for localized abdominal subcutaneous fat reduction. OBJECTIVES: To assess the safety and efficacy of CBL-514 in reducing abdominal subcutaneous fat volume and thickness. METHODS: This Phase IIa, open-label, random allocation study consisted of a 6-week treatment period and follow-up at 4- and 8-weeks following the last treatment. Participants were randomly allocated to 1.2 mg/cm 2 (180 mg), 1.6 mg/cm 2 (240 mg), or 2.0 mg/cm 2 (300 mg) of CBL-514 with up to 4 treatments, each with 60 injections into the abdominal adipose layer. Changes in abdominal subcutaneous fat were assessed by ultrasound at follow-up visits. Treatment-emergent adverse events were recorded. RESULTS: Higher doses of CBL-514 (unit dose: 2.0 and 1.6 mg/cm 2) significantly improved the absolute and percentage reduction in abdominal fat volume (p<0.00001) and thickness (p<0.0001) compared to baseline. Although the COVID-19 pandemic halted some participant recruitment and follow-ups, analysis was unaffected, even after sample size limitations. CONCLUSIONS: CBL-514 injection at multiple doses up to 300 mg with a unit dose of 2.0 mg/cm 2 is safe, well-tolerated and reduced abdominal fat volume and thickness by inducing adipocyte apoptosis. While other procedures exist to treat abdominal fat, they have limitations and may cause complications. At a dose of 2.0 mg/cm 2, CBL-514 safely and significantly reduced abdominal fat volume by 24.96%, making it a promising new treatment for routine, non-surgical abdominal fat reduction in dermatological clinics.

3.
Infect Control Hosp Epidemiol ; : 1-18, 2022 May 20.
Article in English | MEDLINE | ID: covidwho-1852305

ABSTRACT

One of six nursing home residents and staff with positive SARS-CoV-2 tests ≥90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data.

4.
Blood ; 138(SUPPL 1):1628, 2021.
Article in English | EMBASE | ID: covidwho-1770286

ABSTRACT

Background Plasma cell disorders (PCD) are at risk of inadequate immune responses to COVID-19 vaccines due to recognised humoral and cellular immune dysfunction which is multi-factorial and related to host and disease factors. With an estimated risk of 33% mortality from contracting COVID-19 in this population, protection with an anti-SARS-CoV-2 vaccination is critical. Initial extension to vaccination intervals in the United Kingdom to 12 weeks in December 2020 led to concerns that PCD patients would be left vulnerable for an extended period. Methods A clinical audit was performed on measured serological responses in PCD patients after first and second doses of the BNT162b2 and ChAdOx-1 nCoV-19 vaccines. Antibody levels were measured using Elecsys Anti-SARS-CoV-2S assay (Roche) for quantitative detection of IgG Abs, specific for the SARS-CoV-2 spike-protein. Positive cut-off of 0.80 U/mL defined serological response. Testing was performed at (or closest to) 4 and 8-weeks post-dose. Baseline nucleocapsid Ab results were available from previous screening in a subset of patients. All patients on CIT underwent 4-weekly swabs. Clinical information was retrieved from medical records. Results 188 PCD patients (155 multiple myeloma, 18 amyloid, 10 SMM/MGUS, other 5 PCD), median age 64 (range 32-84), had serological assessment after both vaccine doses. Fourteen with previous COVID-19 infection were excluded. Of 174 patients, 112 were tested after first dose. 88% (153) were on chemo-immunotherapy treatment (CIT). Seropositive rate after first dose was 63% (71/112);of those with available negative baseline antibody test, 62% (31/50) seroconverted. After second dose, 89% (154/174) were seropositive;of those with negative baseline antibody, 90% (61/68) seroconverted. Expectedly, paired median titres after second dose were significantly higher than post first dose (n=112, 3.245 U/mL (IQR 0.4-25.55) vs 518 U/mL (IQR 29.40-2187) p<0.0001) (Figure 1A). Of 41 patients seronegative after first dose, 25 (61%) seroconverted after second, though with lower titres than those only requiring one dose (Figure 1B). Active CIT, disease response less than PR, >=4 lines therapy, light-chain disease, male gender and not responding to first dose were significant factors for not responding to two vaccine doses. We explored <400 U/mL as sub-optimal response (in keeping with upcoming booster study eligibility, OCTAVE-DUO(1), also encompassing the lower quartile of reported healthy controls(2)), which included 43% (75/174) patients. Age 70 years, male gender, >=4 lines of treatment were independent predictors of less-than-optimal response (anti-CD38 CIT of borderline significance). Importantly, vaccine dosing intervals classified as =<42 vs >42 days (Figure 1C) or 28 +/- 14 days vs 84 +/- 14 days (excluding n=66 in neither) (Figure 1D) did not show difference in both definitions of response, neither did vaccine type. Fourteen with previous COVID-19 infection responded to one vaccine dose, median titres 2121 U/mL (IQR 23.48- 2500)) rising to median 2500 U/mL (IQR 2500-2500) after second dose (Figure 1E), significantly higher than those without previous infection. Conclusion Serological response to COVID-19 vaccine is lower in PCD patients than reported healthy controls at 63% after first dose, rising to 89% after second dose, despite extended dosing intervals. PCD patients should be prioritised for shorter intervals, as we show that patients seronegative after first dose, respond after second dose. Further work in PCD is needed to understand how Ab levels correlate to neutralisation capability, cellular responses, protection from infection and how long seroconversion lasts to better define correlates of protection. A booster vaccination or prophylactic passive antibody strategy may be required for those identified at risk, shown not to have responded to two vaccine doses or to have less-than-optimal response. Results from these trials will be eagerly awaited. (Figure Presented).

5.
Open Forum Infectious Diseases ; 8(SUPPL 1):S298-S299, 2021.
Article in English | EMBASE | ID: covidwho-1746601

ABSTRACT

Background. Background. Understanding the viral load and potential infectivity of individuals in nursing homes (NH) with repeat positive SARS-CoV-2 tests ≥ 90 days after initial infection has important implications for safety related to transmission in this high-risk setting. Methods. Methods. We collected epidemiologic data by reviewing records of a convenience sample of NH residents and staff with respiratory specimens who had positive SARS-CoV-2 rRT-PCR test results from July 2020 through March 2021 and had a SARS-CoV-2 infection diagnosed ≥ 90 days prior. No fully vaccinated individuals were included. Each contributed one repeat positive specimen ≥ 90 days after initial, which was sent to CDC and retested using rRT-PCR. Specimens were assessed for replication-competent virus in cell culture if Cycle threshold (Ct) < 34 and sequenced if Ct < 30. Using Ct values as a proxy for viral RNA load, specimens were categorized as high (Ct < 30) or low (if Ct ≥ 30 or rRT-PCR negative at retesting). Continuous variables were compared using Wilcoxon signed-rank tests. Proportions were compared using Chi-squared or Fisher's exact tests. Results. Results. Of 64 unvaccinated individuals with specimens from 61 unique NHs, 14 (22%) were sent for culture and sequencing. Ten of 64 (16%) had a high viral RNA load, of which four (6%) were culture positive and none were known variants of interest or concern (Figure 1). Median days to repeat positive test result were 122 (Interquartile range (IQR): 103-229) and 201 (IQR: 139-254), respectively, for high versus low viral load specimens (p=0.13). More individuals with high viral loads (5/10, 50%) reported COVID-19 symptoms than with a low viral load (1/27, 4%, p=0.003). Most individuals (46/58, 79%) were tested following known or suspected exposures, with no significant differences between high and low viral load (p=0.18). Conclusion. In this study, nearly 1 in 6 NH residents and staff with repeat positive tests after 90 days demonstrated high viral RNA loads and viable virus, indicating possible infectivity. While individuals with high RNA viral load may be more likely to be symptomatic, distinguishing asymptomatic individuals who have high viral loads may be difficult with timing since initial infection, other test results, or exposure history alone.

6.
Heart Lung and Circulation ; 30:S264-S265, 2021.
Article in English | EMBASE | ID: covidwho-1734425

ABSTRACT

Background: The COVID-19 pandemic has paved the way for the introduction of telehealth clinic consultations. Objectives: To examine the impact of the introduction of telehealth/telephone consultation in the COVID-19 era on clinic attendance rates in an adult congenital heart disease (ACHD) clinic. Methods: Single centre audit study to compare clinic attendance rates in a large tertiary ACHD clinic over a 12-month period immediately pre-telehealth/telephone (3/5/19-17/3/20) and post-telehealth/telephone (24/3/20-2/3/21). The overall fail to attend rate for the pre-telehealth/telephone and post-telehealth/telephone periods were compared using a chi-squared test. The ACHD clinic is held once a week except for one week per month. Patients receive lifelong follow-up and are reviewed on an annual basis, on average. Results: In the pre-telehealth/telephone period, there were 409 failures to attend for 1937 clinic bookings resulting in a 21.1% (409/1937) failure rate. In the post-telehealth/telephone period, there were 215 failures to attend for 1594 clinic bookings resulting in a 13.5% (215/1594) failure rate. There was a significant reduction in the fail to attend rate in the post-telehealth/telephone period compared with the pre-telehealth/telephone period (p<0.00001). Further research is currently underway to characterise (including geographical demographics) the patients now engaged due to telehealth/telephone consultation and those who still fail to attend. Conclusions: Clinic attendance rates in a tertiary adult congenital heart disease clinic significantly improved after introduction of telehealth/telephone consultation in the COVID-19 era. Further qualitative research is required to determine patient and clinician preferences for the use of telehealth in the ACHD clinic setting.

7.
N Engl J Med ; 386(9): 861-868, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1721753

ABSTRACT

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.


Subject(s)
Aromatherapy/adverse effects , Burkholderia pseudomallei/isolation & purification , Disease Outbreaks , Melioidosis/epidemiology , Aerosols , Brain/microbiology , Brain/pathology , Burkholderia pseudomallei/genetics , COVID-19/complications , Child, Preschool , Fatal Outcome , Female , Genome, Bacterial , Humans , Lung/microbiology , Lung/pathology , Male , Melioidosis/complications , Middle Aged , Phylogeny , Shock, Septic/microbiology , United States/epidemiology
8.
Pediatric cardiology ; : 1-8, 2022.
Article in English | EuropePMC | ID: covidwho-1652126

ABSTRACT

Studies describing gaps in care for youth with congenital heart disease (CHD), focus on those who have returned to care, but rarely those actively missing from care. Our objective was to determine barriers for young adults with CHD actively missing from cardiac care and to re-engage them in care. Retrospective single-center cohort study of cardiology clinic patients ages 15–21 years with CHD between 2012 and 2019 for patients actively missing from care (≥ 12 months beyond requested clinic follow-up). We conducted prospective interviews, offered clinic scheduling information, and recorded cardiac follow-up. Data analyzed using descriptive statistics, univariable, and multivariable logistic regression. Of 1053 CHD patients, 33% (n = 349) were actively missing. Of those missing, 58% were male and median age was 17 years (IQR 16–19). Forty-six percent were Non-Hispanic White, 33% Hispanic, and 9% Black. Moderately complex CHD was in 71%, and 62% had private insurance. Patients with simple CHD, older age at last encounter (18–21), and scheduled follow-up > 12 months from last encounter were more likely to be actively missing. Interviews were completed by 125 patients/parents (36%). Lack of cardiac care was reported in 52%, and common barriers included: insurance (33%), appointment scheduling (26%), and unknown ACHD center care (15%). Roughly half (55%) accepted appointment information, yet only 3% successfully returned. Many patients require assistance beyond CHD knowledge to maintain and re-engage in care. Future interventions should include scheduling assistance, focused insurance maintenance, understanding where to obtain ACHD care, and educating on need for lifelong care.

9.
Indian Journal of Hematology and Blood Transfusion ; 37(SUPPL 1):S146-S147, 2021.
Article in English | EMBASE | ID: covidwho-1635559

ABSTRACT

Introduction: Coagulopathy in COVID-19 progresses from initialpulmonary microthrombi without systemic coagulation activation to asystemic hypercoagulable stage with widespread activation of coagulation and then to a hypocoagulable picture seen in later phases ofthe disease.Aims &Objectives: We decided to conduct this study because of thesevere infections in 2021 compared to 2020 to understand theCoagulopathy in COVID-19 among our population using Thromboelastography (TEG) and V curve.Materials &Methods: All adult patients with a confirmed COVID-19 and TEG report were recruited in the study and followed up fortwo months. Citrated Kaolin TEG parameters included were R and Ktime, alpha angle, maximum amplitude, clotting index, lysis 30. Thefirst-degree velocity curve of (V curve) TEG which extrapolatesthrombin generation potential with maximum rate of thrombin generation and time as well as thrombin generated. Comparison betweensurvivors and thromboembolisms were made with TEG parameters.Result: Study included 43 patients after excluding three patients.Average age was 58.34 (± 15.35) and majority of them were males(34/43). TEG as well as V-curve were hypercoagulable compared toage matched reference range. Systemic hypercoagulable stage (34/43)and interestingly 13/34 patients had secondary fibrinolysis activity.Mortality rate and thrombotic incidents was 32.56% and 30.23%respectively. Risk factors for mortality were MA, LY 30, TG,Hypercoagulable TEG (OR-7.36), D Dimer (OR-1.40) and Thrombosis (OR-1.37). Incidents of Thrombosis in decreasing order wasacute coronary syndrome (n = 10), DVT with PTE (n = 2) and MCAinfarction (n-1). LY 30 was associated with an increased thromboticrisk (OR-15.3, r = 0.122, Correlation-0.40, P = 0.02). Repeat TEGwas performed in 11 patients which was consistent with a hypercoagulable picture even after 5 days of thromboprophylaxis.Conclusions: TEG is useful in diagnosing and categorizing Coagulopathy associated with COVID-19.

10.
Circulation ; 144(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1630426

ABSTRACT

Introduction: Cardiac complications of COVID-19 include acute cardiac injury, myopericarditis, cardiomyopathy and arrhythmias. This study aimed to describe the incidence of cardiac complications in patients admitted to hospital with COVID-19 in Australia. Methods: AUS-COVID is a multicentre observational cohort study across 21 Australian hospitals including all index hospitalisations with laboratory-proven COVID-19 in patients aged 18 years or older. All consecutive patients entered in the AUS-COVID Registry by 28 January 2021 were included in the present study. Results: Six hundred and forty-four hospitalised patients (62.5 ± 20.1 years old, 51.1% male) with COVID-19 were enrolled in the study. Overall in-hospital mortality was 14.3%. Twenty (3.6%) patients developed new atrial fibrillation or flutter during admission and 9 (1.6%) patients were diagnosed with new heart failure or cardiomyopathy. Three (0.5%) patients developed high grade atrioventricular (AV) block. Two (0.3%) patients were clinically diagnosed with pericarditis or myopericarditis. Among the 295 (45.8%) patients with at least one troponin measurement, 99 (33.6%) had a peak troponin above the upper limit of normal (ULN). In-hospital mortality was higher in patients with raised troponin (32.3% vs 6.1%, p<.001). New onset atrial fibrillation or flutter (6.4% vs 1.0%, p=.001) and troponin elevation above the ULN (50.3% vs 16.4%, p<.001) were more common in patients 65 years and older. There was no significant difference in the rate of cardiac complications between males and females. Conclusions: Among patients with COVID-19 requiring hospitalisation in Australia, troponin elevation was common but clinical cardiac sequelae were uncommon. The incidence of atrial arrhythmias and troponin elevation was greatest in patients 65 years and older.

11.
Circulation ; 144(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1630425

ABSTRACT

Introduction: To assess whether hypertension is an independent risk factor for mortality amongst patients hospitalised with COVID-19 and to evaluate the impact of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on mortality in patients with a background of hypertension. Methods: This observational cohort study included all consecutive index hospitalisations with laboratory proven COVID-19 aged 18 years or older across 21 Australian hospitals entered in the AUS-COVID Registry by 22nd January 2021. Patients were excluded if their past medical or medication history was not available or if they were transferred to another hospital in which case mortality outcomes were not available. Registry data were analysed for in-hospital mortality in patients with comorbidities including hypertension, and baseline treatment with ACE inhibitors or ARBs.Results: 546 consecutive patients (62.9±19.8 years old, 51.8% male) hospitalised with COVID-19 were enrolled. In the multivariable model, significant predictors of mortality were age (aOR 1.09, 95% CI 1.07-1.12, p<.001), heart failure or cardiomyopathy (aOR 2.71, 95% CI 1.13-6.53, p=.026), chronic kidney disease (aOR 2.33, 95% CI 1.02-5.32, p=.044) and chronic obstructive pulmonary disease (aOR 2.27, 95% CI 1.06-4.85, p=.035) (Figure 1). Hypertension was the most prevalent comorbidity (49.5%) but was not independently associated with increased mortality (aOR 0.92, 95% CI 0.48-1.77, p=.81). Amongst patients with hypertension, ACE inhibitors (aOR 1.37, 95% CI 0.61-3.08, p=.61) and ARBs (aOR 0.64, 95% CI 0.27-1.49, p=.30) did not affect mortality. Conclusions: In patients hospitalised with COVID-19, pre-existing hypertension was the most prevalent comorbidity but was not independently associated with mortality. Similarly, the baseline use of ACE inhibitors or ARBs had no independent association with in-hospital mortality.

12.
Open forum infectious diseases ; 8(Suppl 1):S298-S299, 2021.
Article in English | EuropePMC | ID: covidwho-1602640

ABSTRACT

Background Background. Understanding the viral load and potential infectivity of individuals in nursing homes (NH) with repeat positive SARS-CoV-2 tests ≥ 90 days after initial infection has important implications for safety related to transmission in this high-risk setting. Methods Methods. We collected epidemiologic data by reviewing records of a convenience sample of NH residents and staff with respiratory specimens who had positive SARS-CoV-2 rRT-PCR test results from July 2020 through March 2021 and had a SARS-CoV-2 infection diagnosed ≥ 90 days prior. No fully vaccinated individuals were included. Each contributed one repeat positive specimen ≥ 90 days after initial, which was sent to CDC and retested using rRT-PCR. Specimens were assessed for replication-competent virus in cell culture if Cycle threshold (Ct) < 34 and sequenced if Ct < 30. Using Ct values as a proxy for viral RNA load, specimens were categorized as high (Ct < 30) or low (if Ct ≥ 30 or rRT-PCR negative at retesting). Continuous variables were compared using Wilcoxon signed-rank tests. Proportions were compared using Chi-squared or Fisher’s exact tests. Results Results. Of 64 unvaccinated individuals with specimens from 61 unique NHs, 14 (22%) were sent for culture and sequencing. Ten of 64 (16%) had a high viral RNA load, of which four (6%) were culture positive and none were known variants of interest or concern (Figure 1). Median days to repeat positive test result were 122 (Interquartile range (IQR): 103–229) and 201 (IQR: 139–254), respectively, for high versus low viral load specimens (p=0.13). More individuals with high viral loads (5/10, 50%) reported COVID-19 symptoms than with a low viral load (1/27, 4%, p=0.003). Most individuals (46/58, 79%) were tested following known or suspected exposures, with no significant differences between high and low viral load (p=0.18). Conclusion In this study, nearly 1 in 6 NH residents and staff with repeat positive tests after 90 days demonstrated high viral RNA loads and viable virus, indicating possible infectivity. While individuals with high RNA viral load may be more likely to be symptomatic, distinguishing asymptomatic individuals who have high viral loads may be difficult with timing since initial infection, other test results, or exposure history alone. Disclosures John A. Jernigan, MD, MS, Nothing to disclose.

13.
23rd International Conference on Engineering and Product Design Education, E and PDE 2021 ; 2021.
Article in English | Scopus | ID: covidwho-1589469

ABSTRACT

This paper will examine how remote communication tools such as “BlueJeans” or Microsoft “Teams” can be employed in a studio project to enhance the undergraduate educational experience in the context of remote class instruction. Junior level students in the School of Industrial Design at the Georgia Institute of Technology take specific themed studio courses, one of which is “Health and Well Being” which is being taught in a “hybrid” delivery mode in response to COVID related concerns. Recognizing that remote instruction could compromise learning opportunities, the course was organized to follow a model used professionally by this author when managing multiple team projects as a design director. Three projects championed by outside sponsors included (1) the design of paramedic equipment transport solutions;(2) systems to reduce the acuity of Nexxspan medical headwalls in behaviour health or end-of-life scenarios;(3) and development of a system for arterial dialysis. Sponsors included a former fireman/paramedic/alumni, a commercial company that offers a range of hospital equipment management products and a transplant surgeon with the School of Medicine at the University of South Carolina. Sponsors pitched the projects to the students at the outset of the semester. Students formed teams of 3-4 students based on their affinity to individual projects;5 teams being fielded out of a class of 20 students. Teams initially met in person or remotely with their project sponsors to better understand their chosen projects. Users and/or subject matter experts were interviewed remotely during the research process. Remote sessions were held twice weekly with each team to review progress and provide feedback/advice. Each team presented their work to sponsors and the class as a whole at three points during the semester using the BlueJeans application to summarize research, concept development and concept refinement/documentation. In comparison with comparable projects conducted during previous semesters, it was observed that the option to participate remotely permitted outside sponsors to be MORE available to students with transportation and parking no longer being an impediment. Furthermore, by scheduling focused feedback/input to individual teams via a remote application, the effectiveness and efficiency of the instruction process was optimized for both the students and instructor. The drawbacks of this remote instruction relate more to issues of poor team dynamics or individual students lacking key design skills (which might be better addressed in person). Additionally, it has been observed that students not meeting face-face in studio limits peer-peer competition which decreases individual motivation for improvement in problematic students. © PDE 2021.

14.
Blood ; 138:3823, 2021.
Article in English | EMBASE | ID: covidwho-1582409

ABSTRACT

INTRODUCTION We have previously described AUTO1, a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR-T immune toxicity and improve engraftment. Its clinical activity has been tested in r/r paediatric and adult B-ALL. Cumulatively, this data confirms the intended function of the receptor, with low levels of CRS/ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Recently, CAR-T therapy has been explored in indolent lymphomas such as follicular (FL) and mantle cell lymphoma (MCL), but a high incidence of toxicity including Grade 3-4 ICANS has been reported. We have initiated testing of AUTO1 in the setting of indolent and high-grade B-NHL and CLL (NCT02935257). METHODS Manufacturing: CAR T-cell products were generated using a semi-automated closed process from non-mobilised leukapheresate. Study design: Subjects ≥ 16y underwent lymphodepletion with fludarabine (30mg/m 2 x3) and cyclophosphamide (60mg/kg x1) prior to AUTO1 infusion, with the exception of the DLBCL cohort who additionally received a single dose of pembrolizumab (200mg) on day -1 to potentiate CAR-T expansion. AUTO1 dose varies based on the indication. Split dosing of 230 x10

15.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-293261

ABSTRACT

SARS-CoV-2, a novel Betacoronavirus, was first reported circulating in human populations in December 2019 and has since become a global pandemic. Recent history involving SARS-like coronavirus outbreaks (SARS-CoV and MERS-CoV) have demonstrated the significant role of intermediate and reservoir hosts in viral maintenance and transmission cycles. Evidence of SARS-CoV-2 natural infection and experimental infections of a wide variety of animal species has been demonstrated, and in silico and in vitro studies have indicated that deer are susceptible to SARS-CoV-2 infection. White-tailed deer (Odocoileus virginianus) are amongst the most abundant, densely populated, and geographically widespread wild ruminant species in the United States. Human interaction with white-tailed deer has resulted in the occurrence of disease in human populations in the past. Recently, white-tailed deer fawns were shown to be susceptible to SARS-CoV-2. In the present study, we investigated the susceptibility and transmission of SARS-CoV-2 in adult white-tailed deer. In addition, we examined the competition of two SARS-CoV-2 isolates, representatives of the ancestral lineage A (SARS-CoV-2/human/USA/WA1/2020) and the alpha variant of concern (VOC) B.1.1.7 (SARS-CoV-2/human/USA/CA_CDC_5574/2020), through co-infection of white-tailed deer. Next-generation sequencing was used to determine the presence and transmission of each strain in the co-infected and contact sentinel animals. Our results demonstrate that adult white-tailed deer are highly susceptible to SARS-CoV-2 infection and can transmit the virus through direct contact as well as vertically from doe to fetus. Additionally, we determined that the alpha VOC B.1.1.7 isolate of SARS-CoV-2 outcompetes the ancestral lineage A isolate in white-tailed deer, as demonstrated by the genome of the virus shed from nasal and oral cavities from principal infected and contact animals, and from virus present in tissues of principal infected deer, fetuses and contact animals.

16.
Clin Infect Dis ; 2021 Nov 28.
Article in English | MEDLINE | ID: covidwho-1545912

ABSTRACT

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the COVID-19 pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. METHODS: Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. RESULTS: From December 14, 2020 to April 30, 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21-66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11-78 days) before MIS-A onset. All 20 patients had laboratory evidence of SARS-CoV-2 infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6-45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. CONCLUSIONS: Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring.

17.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-292925

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that has had significant impacts on human health and economies worldwide. SARS-CoV-2 is highly transmissible and the cause of coronavirus disease 2019 (COVID-19) in humans. A wide range of animal species have also been shown to be susceptible to SARS-CoV-2 infection by experimental and/or natural infections. Domestic and large cats, mink, ferrets, hamsters, deer mice, white-tailed deer, and non-human primates have been shown to be highly susceptible, whereas other species such as mice, dogs, pigs, and cattle appear to be refractory to infection or have very limited susceptibility. Sheep (Ovis aries) are a commonly farmed domestic ruminant that have not previously been thoroughly investigated for their susceptibility to SARS-CoV-2. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cell cultures and experimental challenge of sheep to investigate their susceptibility to SARS-CoV-2. Our results showed that sheep-derived cell cultures support SARS-CoV-2 replication. Furthermore, experimental challenge of sheep demonstrated limited infection with viral RNA shed in nasal and oral swabs primarily at 1-day post challenge (DPC), and also detected in the respiratory tract and lymphoid tissues at 4 and 8 DPC. Sero-reactivity was also observed in some of the principal infected sheep but not the contact sentinels, indicating that transmission to co-mingled naive sheep was not highly efficient;hovewer, viral RNA was detected in some of the respiratory tract tissues of sentinel animals at 21 DPC. Furthermore, we used challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the B.1.1.7-like alpha variant of concern (VOC), to study competition of the two virus strains. Our results indicate that sheep show low susceptibility to SARS-CoV-2 infection, and that the alpha VOC outcompeted the ancestral lineage A strain.

20.
Int Nurs Rev ; 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1532804

ABSTRACT

AIM: To explore Master of Nursing students' perspectives toward the impact of coronavirus disease 2019 (COVID-19) on the advanced practice nurse preparatory education and practice. BACKGROUND: Like many nursing education programmes, the advanced practice nurse preparatory training was greatly affected and had to radically change to adapt to the disruptions caused by the pandemic. The COVID-19 pandemic has created a strain on the healthcare system and advanced practice nurses have been expected to modify their normal practice to provide care in unprecedented ways. METHODS: The study used a descriptive qualitative design. Semi-structured video-conference interviews were conducted in an autonomous university (June-July 2020). The recruitment of participants (n = 14) concluded upon data saturation. A thematic analysis was conducted. The COnsolidated criteria for REporting Qualitative research (COREQ) guidelines were used. FINDINGS: Three main themes were identified: (1) overcome adversity through innovation, (2) acceptance of remote learning and (3) versatility of advanced practice nurses in an ongoing pandemic. Each theme was further explained by two subthemes to further elucidate the impact of COVID-19 on the advanced practice nurse preparatory training and practice. DISCUSSION: The evolution of the advanced practice nurse preparatory education catalysed by the COVID-19 pandemic brought on innovation. The ability of advanced practice nurses to adapt to evolving healthcare needs was also highlighted. CONCLUSION: Although face-to-face teaching and services are gradually returning, some innovations that arose during the pandemic may be worth keeping. IMPLICATIONS FOR NURSING: Nursing educators in higher education institutions can benefit from adopting technology to mitigate the challenges posed by the ongoing pandemic IMPLICATIONS FOR NURSING POLICY: Nurse leaders should review the role of advanced practice nurses to determine how best to capitalise on their practice to meet rising healthcare needs.

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