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Background & Aim: Despite the successful implementation of vaccines worldwide, COVID-19 remains a risk in patients with a compromised immune system. Emerging viral variants have also reduced the effectiveness of monoclonal antibody therapies in these patients. New treatment options are therefore required to improve clinical outcomes. Methods, Results & Conclusion(s): T cell immunotherapy has proven effective for the treatment of a number of refractory viral diseases in patients with a compromised immune system. We have now completed the manufacture of a bank of SARS-CoV-2 specific T cells and commenced an open-label phase I clinical trial at the Royal Brisbane and Women's Hospital, Australia. Patients enrolled in the study receive two doses of partially HLA-matched allogeneic T cells at a fortnightly interval. We have thus far recruited and treated three immune compromised patients with SARS-CoV-2 T cells. In two of the three patients treated thus far, the administration of T cell therapy was coincident with the clearance of viral load after 28 days. Viral clearance in these patients was also associated with an increase in circulating SARS-CoV-2 specific T cells. Our preliminary observations suggest that SARS-CoV-2 specific T cell therapy is well tolerated and has the potential to impact viral control in immune compromised patients.Copyright © 2023 International Society for Cell & Gene Therapy
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stress. We studied admissions, readmission (RAD) rates, and demographics of ALD patients before and after the onset of the COVID-19 pandemic. Methods: We reviewed the number of hospitalizations before and after the onset of the COVID-19 pandemic for ALD at four teaching hospitals in the Northwell Health System, two bordering New York City to the east (region A) and two in NYC (region B). Coding data of hospital discharges for ALD (alcoholic hepatitis, alcohol-associated cirrhosis, nonspecific alcohol liver disease) during the 14 months between January 2019 and February 2020 (period 1) were compared to those between June 2020 and July 2021 (period 2) for admissions, RAD, and demographics. Data from March to May 2020 were excluded due to New York City lockdown, limited and delayed access to health care due to COVID-19 pandemic. The Fisher's exact test and Mann- Whitney test are used for statistic comparisons. Results: The number of hospitalizations for ALD increased by 32% during the COVID-19 pandemic. However, the increase was only observed in region A, but not in region B (55% vs -1%). With the onset of the pandemic, the median age for ALD admissions decreased by 4.5 years overall, significantly in region B (7.5 years), but not in region A (2 years). In both regions, the percentage of the white race admissions also decreased. No significant difference was observed in the gender distribution, Medicaid insurance status and overall rate of RAD (Table 1). However, the white population had decreased RAD rates from 32% to 17% in region B, the non-white population RAD rates increased from 17% to 31% in region A, and in regions A and B combined (Table 2). Conclusion: Our study shows that admission for ALD increased during the COVID-19 pandemic in areas bordering NYC but not in NYC. These rates differed by race, accompanied with a slight shift to younger age. Our results suggest that observations based on certain communities or regions may not be universally applicable. Future research for the impact of COVID-19 on ALD and other social-economic adaptation should take demographic and geographic variations into consideration. (Table Presented)
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Primary central nervous system (CNS) tumors are a leading cause of death and disability amongst pediatric cancer patients. The early identification of symptom onset is critical in preventing diagnostic delays. In 2018, Akron Children's Hospital published data on our response time to brain tumor diagnosis and launched educational programs in an effort to decrease diagnostic delays. The goal was to reduce the total diagnostic interval (TDI) in our patient population and reduce tumor- and treatment-related morbidities for these patients. Our post intervention group (2018-2021) was drastically affected by the numerous hospital changes secondary to the COVID-19 pandemic. We sought to examine the impact of COVID-19 related changes on TDI and attempted to identify groups at potential increased risk for diagnostic delays due to the unique pandemic constraints. A retrospective chart review was performed on patients at Akron Children's Hospital to evaluate both for pre- (diagnosed Jan 1, 2018-February 29, 2020) and post- COVID-19 (diagnosed Mar 1, 2020-June 8, 2021) groups. Both subsets were evaluated statistically and were similar in all respects including demographics, symptomatology, tumor location, tumor type, and survival. The pre-COVID-19 group demonstrated a median TDI of 43.5 days, while the post-COVID-19 group demonstrated a 30-day median. The TDI for low-grade lesions increased from 32 to 59 days and for high-grade lesions decreased from 60 to 27.5 days in the post-pandemic cohort. Overall, this demonstrates a maintained average time to diagnosis for patients despite the pandemic restrictions in place. In addition, the differences in low vs. high-grade lesions suggest that tumors with a more subtle onset of symptoms were disproportionately affected, and highlight a population for intervention during the continued pandemic.
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Background: In March-April 2020, the New York City (NYC) metropolitan area faced one of the largest COVID-19 outbreaks in the world. During the subsequent citywide and nationwide lockdowns, national alcohol sales reported a 54% increase. We attempted to determine whether the increase in alcohol use led to increase volume of emergency department (ED) visits for alcohol-related illnesses. Methods: Coding data from May 2019 to March 2021 for alcohol-related illnesses, including intoxication, independence, withdrawal, and alcoholic liver disease from six teaching hospitals within the Northwell Health System from three geographic regions was reviewed. The six hospitals represent the region connecting Queens and Long Island (Gr. A), the borough of Staten Island (Gr. B), and the borough of Manhattan (Gr. C). Results: The number of patients that visited the ED for alcohol-related illnesses was 7,343 during the 11 months before April 2020. This number decreased to 5,056 during the 11 months after April 2020, a 31% decrease. Individually, the mean±SD of monthly volume significantly decreased from 290±41 to 174±27 (P<0.0001) in Gr. C and from 211±29 to 132±2 (P<0.0001) in Gr. B, but insignificantly decreased in Gr. A from 167±16 to 154±14 (P=0.65). The monthly numbers at the three hospital groups are depicted in image attached. In Gr. A, the monthly volume of cases was unvarying during the 11 months before April 2020 and was essentially unchanged during the pandemic (probability of difference in trend = 0.29), after showing a drop in April corresponding with New York State's severe COVID-19 outbreak. A similar drop during April also occurred in Gr. B and C. In Gr. B, the monthly volume of cases partially recovered after April, but resumed its slight insignificant decrease before April (probability of difference in trend = 0.79). In Gr. C, the monthly volume also partially recovered after April, but showed an upward trend, contrasting the decrease prior to the April outbreak (probability of difference in trend <0.0001). Conclusion: Our study showed that the ED visits for alcohol-related illnesses during the COVID-19 pandemic did not increase in these three neighborhoods of NYC. It suggested that communities may have had varied behavioral responses and the differences warrant further investigation. Future research of the impact of COVID-19 on alcohol-related social-medical issues is urged to take such geographic difference into consideration.
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COVID-19 is a novel disease caused by SARS-CoV-2 which has conquered the world rapidly resulting in a pandemic that massively impacts our health, social activities, and economy. It is likely that vaccination is the only way to form "herd immunity" and restore the world to normal. Here we developed a vaccine candidate for COVID-19 based on the virus-like particle AP205 displaying the spike receptor binding motif (RBM), which is the major target of neutralizing antibodies in convalescent patients. To this end, we genetically fused the RBM domain of SARS-CoV-2 to the C terminus of AP205 of dimerized capsid proteins. The fused VLPs were expressed in E. coli, which resulted in insoluble aggregates. These aggregates were denatured in 8 M urea followed by refolding, which reconstituted VLP formation as confirmed by electron microscopy analysis. Importantly, immunized mice were able to generate high levels of IgG antibodies recognizing eukaryotically expressed receptor binding domain (RBD) as well as spike protein of SARS-CoV-2. Furthermore, induced antibodies were able to neutralize SARS-CoV-2/ABS/NL20. Additionally, this vaccine candidate has the potential to be produced at large scale for immunization programs.
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INTRODUCTION: Coronavirus disease-19 (COVID-19) is associated with a prothrombotic state and increased incidence of thromboembolic disease. Despite limited evidence, many ICUs have implemented increased prophylactic anticoagulation dosing protocols. However, anticoagulant medications increase the risk of bleeding and warrant additional monitoring. As a result, based on the Thromboembolism and Anticoagulant Therapy During the COVID-19 Pandemic: Interim Clinical Guidance from the Anticoagulation Forum, the study site increased doses of venous thromboembolism prophylaxis (VTEP) to a standard dose of enoxaparin 40 mg subcutaneous (subcut) Q12H for critically ill patients with COVID-19. For patients less than 60 kg, the dose was decreased to enoxaparin 30 mg subcut Q12H. Additionally, anti-Xa level monitoring was utilized to enhance monitoring for patients receiving enoxaparin. METHODS: This retrospective, observational study aimed to describe the anti-Xa level findings and enoxaparin dose adjustment needs. Patients with an estimated creatine clearance of less than 30 mL/min were excluded. Data collection included weight, serum creatinine, enoxaparin dose, anti-Xa levels, peak D-dimer, incidence of pulmonary emboli (PE), deep vein thrombosis (DVT), major bleeding, and minor bleeding, and ICU length of stay (LOS), hospital LOS, and mortality. Data below are presented as median (IQR). RESULTS: Seventeen adults were in the included and 76.5% (n=13) were started on enoxaparin 40 mg subcut Q12H. Twenty-three anti-Xa levels drawn at steady state. Of those, 82.6% (n=19) were within goal range, 8.7% (n=2) were below goal range, and 8.7% (n=2) were above goal range. Peak D-dimer was 2594 ng/mL (1575.5, 13086.3), two patients (10%) had a DVT, and no PEs were detected. Neither of the patients were receiving enoxaparin for VTEP at the time of the DVT. One patient (5%) had minor bleeding and no major bleeding was observed. The ICU LOS was 7 days (5, 15). Prior to the implementation of increased enoxaparin dosing, 4 anti-Xa levels were drawn for 4 patients on enoxaparin 40 mg subcut Q24H and 3 (75%) were below goal range. CONCLUSIONS: In conclusion, when utilizing increased doses of enoxaparin for VTEP, the majority of anti-Xa levels were within goal range and only 1 patient experienced minor bleeding.
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Background and Aim: The aerosol-generating nature of gastroscopy has prompted a revision of endoscopic standard operating procedures during the coronavirus disease 2019 (COVID-19) pandemic, the health impacts of which are yet to be determined. Patient outcomes may be affected by restricted endoscopic services (50% reduction in activity in Melbourne, Victoria, performing elective category 1 and 2p procedures only), patient COVID-19 health questionnaires and screening, staffing availability, personal protective equipment changes, and health care worker-perceived exposure risk. Additionally, public fear of transmission has led to a reduction in non-COVID-19-related hospital presentations.1 Furthermore, a recent study found that patients presenting with upper gastrointestinal bleeding (UGIB) during COVID-19 had higher rates of hypotension and anemia, higher transfusion requirements, longer hospital lengths of stay, and lower rates of gastroscopy.2 We aimed to evaluate the impact of COVID-19 on presentation and outcomes in patients with UGIB at a single tertiary center in Melbourne. Methods: We conducted a retrospective cohort study of adult patients who presented to our tertiary center with hematemesis and/or melena over the 11-week period from 1 April to 17 June 2020, during the first lockdown period in Melbourne, when there were significant restrictions to endoscopic services (COVID-19 group). Presenting symptoms, comorbidities, laboratory results, hemodynamics, severity scores (Rockall, AIMS65, and Glasgow-Blatchford scores), and patient outcomes were evaluated and compared with those for patients presenting with UGIB during the same period in 2019 (2019 group). Patient outcomes included time to endoscopy, endoscopy procedure duration, endoscopic findings, rebleeding rate, inpatient and 30-day mortality, intensive care unit (ICU) admission, hemodynamic nadir, and transfusion requirements. Results: A total of 27 patients were admitted with UGIB during the COVID-19 period, compared with 25 in the preceding year. Patients in the COVID-19 group were younger (P = 0.05), but baseline demographics, comorbidities, and anticoagulation use were otherwise similar between the two groups. Patients in the COVID-19 group were more likely to present with hematemesis (P < 0.01) and less likely to present with melena (P = 0.02). Platelet count and albumin levels were significantly lower in the COVID-19 group compared with the 2019 group (P = 0.05);laboratory results and hemodynamics were otherwise similar between the two groups at presentation. Rockall, AIMS65, and Glasgow-Blatchford scores were also similar. Both groups were equally likely to receive gastroscopy. Etiology of UGIB at endoscopy was similar. Transfusion requirement, nadir hemoglobin level, and rebleed rates were similar between the two groups, although a subgroup analysis of those swabbed for COVID-19 showed a greater reduction in hemoglobin level compared with the 2019 group (P = 0.03). There were no differences in ICU admissions, inpatient and 30-day mortality, or length of stay. There was a non-significant trend towards longer anesthetic preparation time for the COVID-19 group, but endoscopic procedure length was similar in the two groups. This was also similar in the subgroup analysis of the six patients who were swabbed for COVID-19 during their UGIB admission. Conclusion: Our study showed that patients were more likely to present with hematemesis than melena and that hemoglobin reduction was significantly greater during COVID-19 than in the preceding year. However, measures of severity at presentation, ICU admission, endoscopic findings, and patient outcomes, including timing to endoscopy, length of hospital stay, and mortality, were similar. Our data suggest that the imposed restrictions to endoscopic services and general public concerns about COVID-19 did not adversely affect patient outcomes during the first COVID-19 wave. This is in direct contrast to the findings of a study in New York City, an epicenter of the global COVID-19 pandemic, which reported signi icantly worse patient outcomes during COVID-19,2 and suggests that COVID-19 inpatient burden may be the primary driver accounting for these findings. At the time of writing, Melbourne is amid a second and far more serious wave of COVID-19, with more than six times the daily confirmed case rate necessitating a more stringent lockdown period. Data will be updated to include and contrast this second lockdown period and will be presented at Australian Gastroenterology Week.
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Background and Aim: Public hospital outpatient departments are a critical interface between acute and specialist hospital services and primary care. Failure of patients to attend is an expensive and persistent issue worldwide, with reported did-not-attend (DNA) rates of up to 30% in some centers. Non-attendance is influenced by many factors, such as logistics in getting to the hospital, work commitments, financial hardship, transportation access, and competing health interests. Telehealth has been available for some years, but its implementation and uptake have been limited. Telehealth is defined as “information and communications technologies to deliver health and transmit health information over both long and short distances,”1 and it can be conducted via videoconferencing or telephone. It represents an attractive model to increase outpatient clinic appointments, which is important given the long waiting times for many clinics. Telehealth also provides avenues to continue critical outpatient management during the coronavirus disease 2019 (COVID-19) pandemic and for ongoing clinical management for furloughed or isolated staff who can still be engaged in outpatient care. At our institution, the COVID-19 pandemic stimulated the immediate and almost universal implementation of the telehealth model of care for outpatient appointments. We aimed to evaluate the experience of the telehealth model in the first 3 months of the COVID-19 pandemic in Victoria, focusing on the impact of telehealth on the number of scheduled appointments and clinic DNA rates. Methods: Over a 9-week period during the first COVID-19 lockdown in Melbourne, scheduled appointment numbers and patient attendance rates at 13 gastroenterology and hepatology outpatient clinics at a single tertiary hospital were evaluated through the hospital's online patient administration system, following rapid implementation of the telehealth model of outpatient care. Appointment numbers and attendance were compared with the average attendance rate over the same period in the preceding 5 years. Data collected included patient DNA rates for every scheduled clinic and appointment type (videoconferencing, telephone, or face-to-face consultation). Results: A total of 2626 outpatient clinic appointments were scheduled during the first 9-week COVID-19 lockdown, with 2237 appointments (85%) attended and 389 DNAs (15%), an improvement of 2.2% in attendance rate compared with the average attendance rate during the same 9-week period in the preceding 5 years (P = 0.035). Of the 2626 appointments, 1319 (50%) were video consultations, and 1307 (50%) were telephone consultations. In the preceding 5 years, an average of 2304 outpatient clinic appointments (322 fewer appointments) were scheduled during the same 9-week period, with 1912 appointments (83%) attended and 392 (17%) not attended. Of these 2304 appointments, 2271 (99%) were face-to-face consultations and only 33 (1%) were video consultations. Attendance rates differed according to clinic type. Compared with previous years, outpatient clinics with significantly lower DNA rates during COVID-19 included combined general gastroenterology (15% vs 20%, P = 0.014), satellite inflammatory bowel disease (2% vs 10%, P = 0.033), satellite liver clinic (20% vs 28%, P = 0.198), and privatized liver clinic (13% vs 18%, P = 0.051). Clinics with higher numerical DNA rates included hepatoma (18% vs 12%, P = 0.731) and weight management (20% vs 15%, P = 0.343). When evaluating the appointment type, we found that consultations carried out by telephone resulted in a significantly lower DNA rate, compared with video consultations (9% vs 21%;P < 0.001). Furthermore, an additional 37 clinic lists occurred during this 9-week period, equivalent to four additional lists per week, compared with the average number in the preceding 5 years. Conclusion: Despite the upheaval of clinical services during the COVID-19 pandemic, the major and rapid systems change to overhaul outpatient clinics to an almost exclusively telehealth model was highly succes ful. A total of 1319 video consultations occurred during the 9-week period, compared with just 43 in the preceding year, demonstrating the rapid and widespread implementation of telehealth. Importantly, there was a significant overall reduction in DNA rates, by 2.2%, using the telehealth model. Phone calls were particularly effective for clinic consultations, with DNA rates of only 9.0%. Telehealth has the potential to improve outpatient clinic attendance and efficiency, and our data strongly advocate for ongoing support for telehealth models, including both video and telephone consultation, beyond the COVID-19 era.
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Background and Aims: With an emphasis now on treat to target care in inflammatory bowel disease (IBD) and a focus on strict control of inflammation, IBD management has become more dynamic, and regular monitoring is required to optimize care. This can be burdensome for patients;faceto- face clinic appointments often require absenteeism from work, which can create barriers to accessing care. In the setting of the coronavirus 2019 (COVID-19) pandemic, much of outpatient IBD care has rapidly transitioned to a telehealth model. Our aims were to (i) assess patient satisfaction with the telehealth platform for IBD appointments in the COVID-19 period;(ii) review the failure to attend clinic rates for telehealth appointments during COVID-19, compared with a similar period before COVID-19;(iii) review rates of work absenteeism among patients attending telehealth appointments during COVID-19, compared with a similar period before COVID-19;and (iv) explore patients' beliefs with respect to the safety of their immunomodulatory (IM) therapy in the COVID-19 era, whether they could be reassured by nursing or medical staff with respect to the risks of IM treatment during the COVID-19 pandemic, and their adherence to IM therapy. Methods: At a large tertiary IBD center in Melbourne, Australia, patients with IBD who had attended a scheduled IBD telehealth clinic via video link or phone call from April to June 2020 were invited, via text message, to participate in a web-based survey (ethics approval: QA 20056). The 15-question survey assessed patient satisfaction, concerns, and behavior regarding their treatment and the impact of telehealth clinic appointments on patients' working schedules. The questions regarding patient satisfaction were modeled on the validated Short Assessment of Patient Satisfaction questionnaire. Results: A total of 483 patients were invited to participate in this survey, and 86 have so far completed the survey. Of these, 76 patients (92%) were either satisfied or very satisfied with the treatment they have received, 74 (88%) were satisfied or very satisfied with the health counseling they received, and 74 (88%) agreed or strongly agreed that they had a thorough assessment. There were 69 patients (84%) who were either satisfied or very satisfied with the overall care they received during their telehealth appointment. Failure-to-attend rates were similar for telehealth appointments during the COVID-19 pandemic and for standard appointments during the same period before COVID-19 (10.5% vs 11.4%). Seventeen patients (20%) needed to take time off work to attend a telehealth appointment, compared with 55 (64%) who would previously have taken time off work for a traditional face-to-face clinic appointment. We found that 47 patients (55%) were concerned that their IM therapy put them at increased risk of COVID-19 infection, but most (98%) did not make any alterations to their therapy without the advice of our IBD unit, despite their concerns. After advice received from our IBD unit, most patients (42, 69%) who were concerned about their IM use could be reassured. Conclusion: In this study, patients report high levels of satisfaction with telehealth for their IBD care during the COVID-19 pandemic. This model of care was not associated with a higher rate of clinic non-attendance. Telemedicine reduced work absenteeism when compared with traditional face-to-face clinic appointments. A significant proportion of patients with IBD had concerns about their IM use during the COVID-19 pandemic, but most could be reassured after specialist nursing or medical consultation. We would encourage health providers and payors to consider the expansion of telemedicine beyond the COVID-19 pandemic as an acceptable way of delivering clinic care, and one that is associated with reduced work absenteeism compared with traditional face-to-face outpatient models of care.