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Background and AimsProviding respiratory support (RS) to patients may improve their oxygenation and ventilation, reducing the work of breathing. Emergency department (ED) patients often need RS;COVID-19 has heightened this need. Patients receiving RS may need escalation of their treatment;hence, studies considering the prevalence of escalation are warranted. MethodThis is a protocol for a prospective, observational, multicenter point prevalence study (PPS). Researchers will collect data over 2 days. All participants are adult ED patients needing RS. The setting is four EDs in New Zealand. The primary research question asks, "Which patients receiving RS require escalation of therapy in the ED?" For example, transitioning from conventional oxygen therapy (COT) to intubation is deemed an escalation of therapy. A sample size of 80 participants is required to resolve the primary research question. Secondary research questions: (1) Which patients receive nasal high flow (NHF) in the ED? (2) How is NHF therapy delivered in the ED? (3) What are the effects of NHF therapy on physiological and patient-centered outcomes? Research Electronic Data Capture (REDCap) will be used for data organization. Data will be imported for analysis from REDCap to IBM SPSS software (Statistics for Windows, Version 27.0). Data reporting on the primary outcome shall be considered by analysis of variance, regression modeling, and determination of two treatment effects: Odds Ratio and Number Needed to Treat. Statistical significance for inferential statistics shall use a two-sided alpha with p-values fixed at <= 0.05 level of significance and 95% confidence intervals. This protocol has ethical approval from Massey University, New Zealand. ConclusionThis novel PPS may reduce the evidence and clinical practice gap on RS delivery and ED patient outcomes, as evidenced by the emergence of COVID-19.
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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 Previous studies have reported ongoing cardiac inflammation as assessed by cardiac magnetic resonance imaging (CMR) in a significant proportion of patients several months after recovery from SARS-CoV-2 infection, many of whom had no or minimal symptoms at the time of infection. The aim of SETANTA was to investigate the prevalence of cardiac abnormalities by CMR in unselected patients in Ireland after acute SARS-CoV-2 infection and the correlation with immunological response and biomarkers of coagulation. Methods This was a prospective, observational, communitybased study (clinicaltrials.gov identifier NCT04823182). Consecutive patients recovered from recent SARS-CoV-2 infection at 3 primary care sites were invited to participate. Key inclusion/ exclusion criteria and outcomes of interest are shown in figure 1. Results 100 participants were enrolled (Feb-Sept 2021) at a median of 188 (IQR, 125, 246) days after positive SARSCoV- 2 swab. At index infection, 18% and 35% reported severe and moderate symptoms, respectively;14% were hospitalized;3% were admitted to intensive care for ventilatory support. At enrolment, 83% had ongoing symptoms. 85% had detectable SARS-CoV-2 antigens. CMR and laboratory findings are shown in Figure 1. Clinical follow up to 12 months is ongoing. Conclusion Among an unselected cohort of patients recovered from acute SARS-CoV2 infection, we report a low prevalence of cardiac abnormalities by CMR, despite a high prevalence of moderate/severe symptoms at presentation and a high prevalence of persistent symptoms. Correlation with biomarkers of immunity and coagulation add results of follow up at 12 months will be available for presentation at ICS 2022.
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Nanosensors for the optical detection of dopamine in brain slice has been validated in wildtype C57/C6 mice as well as a Parkinson's model mouse. Using nanosensors, endogenous dopamine release in striatal brain slice is triggered by electrical stimulation and quantified using microscopy. We have established the workflow for this procedure and have prepared a population of Parkinson's and wildtype mice to image in the coming quarter. We have confirmed that the method can quantitatively distinguish dopamine release between subregions of the striatum, a critical step in confirming the method for use in Parkinson's studies. COVID-19 shutdowns stalled research starting in Mar. Research facilities are reopening and the project is expected to resume this quarter.
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Residents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30-60% of all COVID-19 deaths in many European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.
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Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus pandemic, several highly effective and safe vaccines have been produced at remarkable speed. Following global implementation of vaccination programmes, cases of thrombosis with thrombocytopenia following administration of adenoviral vector-based vaccines started being reported. In this review we discuss the known pathogenesis and epidemiology of so-called vaccine induced thrombocytopenia and thrombosis (VITT). We consider the available guidelines, diagnostic laboratory tests and management options for these patients. Finally, we discuss important unanswered questions and areas for future research in this novel pathoclinical entity.
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32 Figure 1ConclusionThe SETANTA study will evaluate the prevalence and characteristics of abnormalities on cardiac MRI in primary care patients in Ireland following recovery from acute SARS-CoV-2 infection and assess correlation with immune response and coagulopathy. Data from the study will help inform the long-term management of patients recovered from SARS-CoV-2 and assist in planning of health care service provision.
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BACKGROUND: Nasal High Flow (NHF) therapy delivers flows of heated humidified gases up to 60 LPM (litres per minute) via a nasal cannula. Particles of oral/nasal fluid released by patients undergoing NHF therapy may pose a cross-infection risk, which is a potential concern for treating COVID-19 patients. METHODS: Liquid particles within the exhaled breath of healthy participants were measured with two protocols: (1) high speed camera imaging and counting exhaled particles under high magnification (6 participants) and (2) measuring the deposition of a chemical marker (riboflavin-5-monophosphate) at a distance of 100 and 500 mm on filter papers through which air was drawn (10 participants). The filter papers were assayed with HPLC. Breathing conditions tested included quiet (resting) breathing and vigorous breathing (which here means nasal snorting, voluntary coughing and voluntary sneezing). Unsupported (natural) breathing and NHF at 30 and 60 LPM were compared. RESULTS: Imaging: During quiet breathing, no particles were recorded with unsupported breathing or 30 LPM NHF (detection limit for single particles 33 µm). Particles were detected from 2 of 6 participants at 60 LPM quiet breathing at approximately 10% of the rate caused by unsupported vigorous breathing. Unsupported vigorous breathing released the greatest numbers of particles. Vigorous breathing with NHF at 60 LPM, released half the number of particles compared to vigorous breathing without NHF.Chemical marker tests: No oral/nasal fluid was detected in quiet breathing without NHF (detection limit 0.28 µL/m3). In quiet breathing with NHF at 60 LPM, small quantities were detected in 4 out of 29 quiet breathing tests, not exceeding 17 µL/m3. Vigorous breathing released 200-1000 times more fluid than the quiet breathing with NHF. The quantities detected in vigorous breathing were similar whether using NHF or not. CONCLUSION: During quiet breathing, 60 LPM NHF therapy may cause oral/nasal fluid to be released as particles, at levels of tens of µL per cubic metre of air. Vigorous breathing (snort, cough or sneeze) releases 200 to 1000 times more oral/nasal fluid than quiet breathing (p < 0.001 with both imaging and chemical marker methods). During vigorous breathing, 60 LPM NHF therapy caused no statistically significant difference in the quantity of oral/nasal fluid released compared to unsupported breathing. NHF use does not increase the risk of dispersing infectious aerosols above the risk of unsupported vigorous breathing. Standard infection prevention and control measures should apply when dealing with a patient who has an acute respiratory infection, independent of which, if any, respiratory support is being used. CLINICAL TRIAL REGISTRATION: ACTRN12614000924651.
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Exhalation , Oxygen Inhalation Therapy/adverse effects , Oxygen Inhalation Therapy/methods , Adult , Breath Tests/methods , COVID-19/therapy , Cannula , Female , Humans , Male , Microscopy, Video , Nose/chemistry , Respiration , Respiratory RateABSTRACT
Background: Cancer patients have many medical and psychosocial needs, which may increase during the coronavirus pandemic and may be difficult to identify or address in the absence of in-person patient visits. We sought to (1) risk stratify hematology/oncology patients using general medicine and cancer-specific methods to identify those at high risk for acute care utilization, (2) measure the correlation between risk-stratification methods, and (3) perform a phone-based needs assessment with intervention for these patients. Methods: Patients were risk-stratified using a general medical health composite score (HCS) embedded in the electronic medical record, and a cancer-specific risk (CSR) stratification based on disease and treatment characteristics. The correlation between HCS and CSR was measured using Spearman's correlation. A multi-disciplinary team developed a focused needs assessment script with recommended interventions for patients categorized as high-risk by either method. The number of patient needs identified and referrals for services made in the first month of outreach are reported. Results: 1,421 patients were risk stratified, with 15% high-risk using HCS and 21.2% high-risk using CSR. Overall correlation between HCS and CSR was modest (r = 0.39). During the first month of the pilot, 287 patients were called for outreach with 245 contacted (85%). Commonly identified needs were financial difficulties (17%), uncontrolled symptoms (15%), and interest in advance care planning (13%), resulting in referral for supportive services for 33% of patients. Conclusions: There is a high burden of unmet medical and psychosocial needs in hematology/oncology patients during the coronavirus pandemic. A phone-based outreach program results in identification of and intervention for these needs, however additional cancer-specific risk models are needed to improve targeting to highrisk patients. This process can serve as a framework for other institutions wishing to implement similar outreach programs during this pandemic.