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Rationale: The FDA granted an emergency use authorization for tixagevimab/ cilgavimab in December 2021 for COVID-19 pre-exposure prophylaxis for individuals that are moderate to severely immunocompromised and has since recommended repeat dosing every 6 months. Given its novelty and resultant hesitation for use among some physicians and patients, our study aimed to observe safety and efficacy of tixagevimab/ cilgavimab, including against one of the newest variants, Omicron BA.5, among our patient population with immunodeficiencies 6 months post-administration via a telephone survey. We hypothesized that adverse outcomes would be minimal and COVID-19 incidence and severity would lessen following tixagevimab/cilgavimab administration. Methods: The Atrium Health Wake Forest Baptist Allergy, Asthma, and Immunology department recruited 15 patients with immunodeficiencies receiving immunoglobulin replacement and tixagevimab/ cilgavimab in March 2022 for a prospective cohort study. A telephone survey was conducted 6 months later regarding tixagevimab/ cilgavimab adverse effects and incidence/severity of COVID infection before and after administration. Results: Two patients experienced minor adverse effects (fatigue, bruising) following tixagevimab/ cilgavimab administration. No severe reactions were reported. Two patients required hospitalization for severe COVID-19 infection prior to tixagevimab/cilgavimab administration, whereas 0 patients required hospitalization for COVID-19 in the 6 months following administration. Four of 5 patients that had COVID-19 following administration had not yet received the bivalent Omicron booster vaccine and 2 had received no COVID-19 vaccines. Conclusions: Tixagevimab/ cilgavimab is associated with minor adverse effects and reduction of COVID-19 severity, albeit perhaps not associated with diminished incidence of newest COVID-19 strains, in a prospective, population-based cohort.
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This web-based survey explored factors associated with food insecurity (FI) among health sciences students during the COVID-19 pandemic. FI was assessed using the USDA 6-item tool. Multivariable logistic regression was used for data analyses. Of the 816 respondents, 74.7% were female and 22.1% were food insecure. An annual income of <$25,000, housing instability, use of a food pantry over the past 12 months, and receiving financial support from family were independently associated with increased odds of being food insecure even after adjusting for other covariates. Further research exploring FI screening and interventions among health sciences university students is needed.
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Introduction: There are no effective treatments for non-active secondary progressive MS (SPMS), which is mediated by compartmentalized CNS inflammation, including activated microglia. We found that fully human anti-CD3 intranasal monoclonal antibody (Foralumab) suppressed disease in a chronic EAE model by dampening microglia and astrocyte inflammation. Nasal Foralumab does not enter the bloodstream or brain. A dose-finding study of nasal Foralumab in controls dosed at 10ug, 50ug and 250ug for 5 days found the drug to be safe with immune effects seen at 50ug. COVID patients dosed with 100ug of nasal Foralumab for 10 days was well-tolerated and exhibited positive effects on blood markers and lung inflammation. Objective(s): To determine if nasal Foralumab has a therapeutic effect on patients with non-active SPMS. Method(s): Two patients were identified with non-active SPMS and sustained clinical progression, despite use of approved DMT. EA1 is a 61-year-old male diagnosed for over 20 years and EA2 is a 42-year-old male diagnosed for 8 years, both last treated with ocrelizumab for 3 years. Treatment occurs in 3-week cycles with intranasal Foralumab 50ug/day administered 3x/week for 2 weeks with 1 week rest. Each cycle, clinical and neurological assessments are repeated, and imaging is repeated every 3 months. Result(s): EA1 has completed 6 months and EA2 has completed 3 months of treatment. To date, there have been no adverse reactions, local irritation, or laboratory abnormalities, and symptom progression has subsided. EA1 is feeling more stable, subjectively, and has noted improvement in lower extremity strength. EDSS, pyramidal motor score and T25FW have stabilized or improved. SDMT and 9HPT were stable during treatment. Microglial activation as measured by [F-18]PBR06 PET scan was significantly reduced 3 months after the start of nasal Foralumab, and this reduction was sustained after 7-week washout and at 6 months. Serum protein measurements of cytokines showed reduction of IFN-gamma, IL-18, IL-1s and IL-6 levels (Olink assay). Cellular immune studies showed increase in CD8 naive cells and decrease in CD8 effector cells, and alteration in gene expression as measured by single cell RNA sequencing. EA2 3-month laboratory and imaging results are pending and will be presented. Conclusion(s): Nasal Foralumab in non-active SPMS patients treated for at least 3 months reduced microglial activation, decreased levels of proinflammatory cytokines, and had positive clinical effects.
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Much home learning research explores the benefits from the perspectives of the child or staff. Less is written about how parent’s view home learning. This became more noticeable recently when nurseries closed because of Covid-19 lockdown. Staff had to design digital home learning activities at speed to help parents support their children’s learning and development while maintaining their relationships with parents. However, we realised we did not know enough about what parents would find helpful and decided to seek their views to categorise their perspectives of home learning and therefore provide more relevant home learning. This paper records a small-scale explorative study in a group of 9 London nurseries where using ethnographic interviews, we sought the views of 15 sets of parents. The study presented some early evidence that parent’s views of home learning can be categorised and suggests an emerging typology made from four groups of parents whose views of home learning reflect their levels of confidence and experience but for some, their views appear to be filtered through the current public debate in England about school readiness. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
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Background: Acute COVID-19 is associated with marked endotheliopathy, VWF-ADAMTS13 axis imbalance and abnormal pulmonary angiogenesis. Persistent endotheliopathy and elevated VWF levels have also been reported in convalescent COVID-19 patients. Aim(s): We investigated the hypothesis that altered pulmonary microvascular architecture may persist in COVID-19 convalescence, resulting in ongoing endothelial cell (EC) activation and VWF-ADAMTS13 axis imbalance, possibly contributing to Long COVID pathogenesis. Method(s): 50 patients (median age 50 years, 60% male, median 68 days post acute COVID-19) were reviewed. Six-minute- walk tests (6MWT) were performed (median 6MWT distance 430m) and plasma samples collected. Plasma VWF:Ag and ADAMTS13 levels were measured by ELISA, and angiogenesis markers assessed by membrane-based antibody array. Result(s): Plasma VWF:Ag levels were significantly elevated in convalescent COVID-19 patients compared to controls (1.1 vs. 0.84 IU/ml;p = 0.004), with 30% (15/50) having VWF:Ag levels above the upper limit of normal. In contrast, plasma ADAMTS13 was significantly reduced in convalescent COVID-19 (median 467 ng/ml vs. 636 ng/ ml p < 0.001). ADAMTS13 levels were significantly lower in those who required hospitalization for acute COVID-19 compared with those managed as outpatients (median 454 ng/ml vs. 513 ng/ml, p = 0.04). Overall, the VWF/ADAMTS13 ratio was significantly elevated in convalescent COVID-19 compared with controls (2.1 vs. 1.1 p = 0.0002) and interestingly was elevated in patients with reduced 6MWT distance (distance >=430 m or <430 m: 1.8 vs. 2.4, p = 0.02). In total, 15 angiogenesis markers were elevated in convalescent COVID-19 compared to controls. An additional 17 angiogenesis (Figure Presented) markers were unique to convalescent COVID-19 and were not found in control plasma (Table 1). Conclusion(s): Collectively, these novel findings demonstrate that endotheliopathy is sustained for months following acute COVID-19 in some patients. As a result, plasma VWF levels are significantly increased;ADAMTS13 levels reduced, and there is ongoing dysregulation of angiogenesis. Further studies will be required to define whether these alterations play a role in Long COVID pathogenesis.
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Background: Severe COVID-19 is associated with marked endothelial cell (EC) activation that plays a key role in immunothrombosis and pulmonary microvascular occlusion. However, the biological mechanisms through which SARS-CoV-2 causes EC activation and damage remain poorly defined. Aim(s): We investigated EC activation in patients with acute COVID-19, and in particular focused on how proteins stored within Weibel-Palade bodies (WPBs) may impact key aspects of disease pathogenesis. Method(s): 39 patients with confirmed COVID-19 were recruited. Weibel-Palade body biomarkers [von Willebrand factor (VWF), angiopoietin-2 (Ang-2) and osteoprotegerin (OPG)] and soluble thrombomodulin (sTM) levels were determined. In addition, EC activation and angiogenesis were assessed in the presence or absence of COVID-19 plasma incubation. Result(s): Markedly elevated plasma VWF:Ag, Ang-2, OPG and sTM levels were observed in acute COVID-19 patients. The increased levels of both sTM and WPB components (VWF, OPG and Ang-2) correlated with COVID-19 severity. Incubation of COVID-19 plasma with ECs triggered enhanced VWF secretion and increased Ang-2 expression (Figure 1). In keeping with the autopsy reports of intussusceptive angiogenesis, treatment with COVID-19 plasma also caused significantly increased EC angiogenesis (Figure 1). Conclusion(s): We propose that as COVID-19 develops, progressive loss of TM and increased sTM, as well as increased Ang-2 expression result in loss of EC quiescence, WPB exocytosis, and a local pro-angiogenic state.
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Introduction: Prone positioning is commonly used when treating ventilated Covid-19 patients. Whilst there have been some reports of ICU proning-related injuries to the brachial plexus well before the pandemic (Goettler et al. 2002), it is usually a very uncommon complication. Despite guidance from the Faculty of Intensive Care Medicine on the care of the proned patient, cases of peripheral neuropathies following ICU admission have significantly increased during the Covid-19 pandemic at our centre (Miller et al. 2021). Nerve injury is associated with reduced quality of life, impaired activity participation and persistent pain (Bailey et al. 2009). Objectives: The aim of this quality improvement project was to identify the effect that new guideline development and related healthcare professional education had on the number and severity of peripheral neuropathies identified following Covid-19 ICU admission. Methods: Between March 2020 and May 2021, we collected clinical data from patients who sustained peripheral neuropathies during their inpatient stay for Covid-19. Data were collected via face-to-face patient assessments within acute nerve clinics or post-ICU rehabilitation wards. A grading system was used to categorise the peripheral nerve injuries into severe, intermediate and mild (Power et al. 2020). Electronic ICU clinical noting was examined to identify the frequency and duration of each proning episode for each patient who presented with nerve injury. Following the first surge in 2020 updated proning guidelines were developed with ICU team leaders and disseminated. This involved face-to-face education of frontline staff. Results: At our centre 93 patients survived Covid ICU between March -June 2020 (surge 1) and 21 of those sustained nerve injury (22.58%). 309 patients survived Covid ICU between September 2020 -May 2021 (surge 2) and 12 of those sustained nerve injury (3.88%). For patients who sustained nerve injury, the average number of prones changed between surges from 6 to 13. The average duration of each episode of proning changed from 17.8hrs to 18.6hrs. Despite the increase in prone frequency, nerve injury occurrence reduced (proportionate to the number of patients who survived Covid ICU) by 82%. 14/21 (66%) injuries acquired in the first surge were of high grade and 4/ 12 (33%) were of high grade during the second surge. Conclusion: Optimising positioning of the proned ventilated patient may reduce the incidence of nerve injury. However, we must also acknowledge that changes in medical management between surges (i.e. use of dexamethasone, remdesivir) may have contributed to this. Individuals still developed severe injury despite this change in practice. Further research looking into risk factors and further methods of optimising the prone positioning on ICU is warranted to reduce the occurrence of this potentially life-changing injury.
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Introduction A global trial is currently investigating the impact of high-intensity interval training (HIIT) on survival in advanced prostate cancer (the INTERVAL trial). To ensure greater accessibility, we designed a parallel trial (EXACT), to determine the feasibility of exercise in those contraindicated to HIIT. Methods Men with metastatic castrate-resistant prostate cancer being actively treated with androgen deprivation therapy and a novel hormone therapy (abiraterone acetate or enzalutamide) are eligible to participate in 12- weeks of home-based walking and strengthening. Participants complete physical (e.g. 6-min walk test and timed sit-to-stand) and quality of life (e.g. BPI-SF;EQ-5D-5L;FACIT-fatigue;FACT-P) outcomes at baseline (T1), 12 (T2) and 24 weeks (T3). This trial was adapted to enable remote recruitment and delivery during the COVID-19 pandemic. Results To date, 118 patients have been screened, with 33 approached by their clinician to participate. 25 patients have consented, with 12 completing the trial without any intervention-related adverse events and 6 withdrawn. Recruitment and trial delivery was operational throughout the COVID-19 pandemic. Currently positive trends are evident for physical and quality of life outcomes at T2 and T3. Conclusions Although this trial is ongoing, early trends suggest this intervention is safe and feasible for men with advanced castration resistant prostate cancer and could improve physical capacity and quality of life.
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The optimal time to initiate research on emergencies is before they occur. However, timely initiation of high quality research may launch during an emergency under the right conditions. These include an appropriate context, clarity in scientific aims, preexisting resources, strong operational and research structures that are facile, and good governance. Here, Nebraskan rapid research efforts early during the 2020 coronavirus disease pandemic, while participating in the firstuse of U.S. federal quarantine in 50 years, are described from these aspects, as the global experience with this severe emerging infection grew apace. The experience has lessons in purpose, structure, function, and performance of research in any emergency, when facing any threat.
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This paper discusses the methodological challenges in studying health risks that could arise from consuming terrestrial snails infested with pathogenic microorganisms. In Cameroon, snails remain an inexpensive protein source and are collected from free-living environments termed “farms.” Our focus has been on understanding health risks due to the handling and consumption of snails collected from locations that include decaying vegetation and untreated human and household wastes. To complement preliminary field observations and get more in-depth understanding of the existing situation, we adopted a qualitative approach using lived experiences, participant observation, in-depth interviews, and a focus group. We made use of informal settings where snail vendors and consumers narrated their routines and experiences from snail harvesting to consumption and the strategies they use to keep their families safe from foodborne illnesses. The study adopted two frameworks: Soft Systems Methodology to explore and model the “messy” nature of the social system and Social Practice Theory to explore the local practices identified through systemic model. The challenges discussed are set in the context of conducting social research in a developing world situation in a time of social and political tension and a global pandemic (COVID-19). With this in mind, the methodological decisions discussed include the type of enquiry and selection of frameworks, selection of field sites, recruitment and engagement with participants, design of interview instruments, interpretation, and trustworthiness of the study findings. We also discuss the strengths and limitations of using our approach. © The Author(s) 2022.
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Introduction: Severe COVID-19 has been associated with aberrant coagulation factor activities, particularly in patients with a thrombotic event (TE). Management of anticoagulant is critical in the care of hospitalized patients with COVID-19.Hypothesis: Evaluation of a point-of-care (POC), functional, clot-time-based coagulation test to detect the anticoagulant effect of therapeutic unfractionated heparin (UFH) in hospitalized SARS-CoV-2-positive patients who developed a TE. Methods: An IRB-approved analysis of 36 citrated plasma specimens from 26 SARS-CoV-2-positive patients and 10 matched negative controls was performed. A Clotting Time Score (CTS), a measure of factor-specific inhibition (i.e. anticoagulant activity), was derived for each patient. CTS results were compared with traditional coagulation tests. Five UFH COVID-19 samples with low CTS scores (<10) were spiked with uniform dosing of UFH, low molecular weight heparin (LMWH), apixaban, or argatroban and retested to assess anticoagulation response. Results: The CTS detected subtherapeutic UFH anticoagulation levels more frequently in COVID-19 cases compared with controls (76% vs. 17%). Prothrombin Times, activated Partial Thromboplastin Times, anti-Xa levels, and antithrombin activity did not correlate with each other or with the CTS in the COVID-19 samples. CTS correlated with both FV and Factor X activity (R =0.49, Spearman R=-0.68), which form the prothrombinase complex. The CTS was 94% sensitive and 67% specific for the occurrence of TEs in patients on UFH. CTS demonstrated a consistent anticoagulant response only to argatroban (100%) compared with other anticoagulants (60%). Conclusions: The CTS, generated using a novel, low-volume, rapid POC coagulation test is a strong indicator of the therapeutic effect of UFH anticoagulation in COVID-19 patients and may provide a predictive measure of TEs potentially occurring from anticoagulation resistance.
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Background: As secondary bacterial infections have been associated with increased mortality in respiratory virus pandemics, we sought to determine if prior pneumococcal vaccination improves clinical outcomes in COVID-19 patients. Methods: We analyzed an observational registry of patients tested for COVID-19 at the Cleveland Clinic because of symptoms or other qualifying criteria from 3/8/2020-5/8/2020. Overlap propensity-score weighted logistic/linear regressions investigated associations between pneumococcal vaccination status and COVID-19- related clinical outcomes. Results: 18,197 patients (median age 50.2 yrs [IQR 30.4], 40% male, 67% white) were included. 2785 (15.3%) tested SARS-CoV-2-positive and 738(26.5%) were hospitalized. Prior pneumococcal vaccination in SARS-CoV-2 positive patients did not reduce ICU admission, oxygen usage, radiographic infiltrates, or need for mechanical ventilation. Pneumococcal vaccine recipients were less likely to test positive for SARSCoV- 2 (OR 0.77, 95% CI [0.68,0.87]). Pneumococcal vaccine recipients aged 15-65 years testing positive for SARS-CoV-2 had increased risk of hospitalization (OR 1.54 [1.001, 2.38] and death (OR 12.51 [1.92,81.36]) compared to non-recipients, and those >65 years were more likely to develop pneumonia (OR 8.45, 95% CI [1.77,40.42]). Conclusions: Pneumococcal vaccination status serves as a marker of underlying co-morbidities with greater risk of hospitalization and death from COVID-19 for those age 15-65 and of pneumonia for those >65, with no impact on other important adverse outcomes. The reduced prevalence of SARS-CoV-2 among pneumococcal vaccine recipients could reflect off-target vaccine effects or patterns of health behavior that persist despite propensity score adjustments. Our study supports evaluation of vaccination status, and vaccination of those at risk.
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This paper addresses the economic impact of the COVID-19 pandemic by providing timely and accurate information on the impact of the current pandemic on income and poverty to inform the targeting of resources to those most affected and assess the success of current efforts. We construct new measures of the income distribution and poverty with a lag of only a few weeks using high-frequency data from the Basic Monthly Current Population Survey (CPS), which collects income information for a large, representative sample of US families. Because the family income data for this project are rarely used, we validate this timely measure of income by comparing historical estimates that rely on these data to estimates from data on income and consumption that have been used much more broadly. Our results indicate that at the start of the pandemic, government policy effectively countered its effects on incomes, leading poverty to fall and low percentiles of income to rise across a range of demographic groups and geographies. Simulations that rely on the detailed CPS data and that closely match total government payments made show that the entire decline in poverty that we find can be accounted for by the rise in government assistance, including unemployment insurance benefits and the Economic Impact Payments. Our simulations further indicate that of those losing employment the vast majority received unemployment insurance,though this was less true early on in the pandemic, and receipt was uneven across the states, with some states not reaching a large share of their out of work residents. Updated results during the pandemic for a subset of the tables in this article can be found at povertymeasurement.org.