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Background: COVID-19 presents a particular challenge in oncology, as in-person visits and treatments can be delayed during infection and patients are at risk for prolonged viral shedding. Our center uses two consecutive negative PCR tests for patients to return to clinic. As vaccination rates increase, we questioned the need for this strategy vs a time-based clearance approach. Method(s): We identified cancer patients who tested positive for COVID-19 from 10/1/2021 to 3/31/2022 at a single tertiary care center and performed chart review under an IRB-approved protocol. Subgroups were compared using the Welch's t-test and Welch's ANOVA for 2 or > 2 groups, respectively. Result(s): 169 patients were identified. 153 had documented clearance defined as two consecutive negative PCR tests. The mean clearance time was 35.7 days (95% CI 32.3-39.0). There was a trend toward longer clearance time in patients with hematologic vs solid tumors (39.6 vs 33.2, p =.06) and a significant increase in patients treated with B cell depletion (58.0) vs chemo/targeted therapy (35.7, p =.01) or immunotherapy (29.0, p =.004). No significant difference was found by vaccination status or between the Delta and Omicron waves. If defined as one negative test, mean clearance time was 25.9 days (95% CI 23.6- 28.1), and there was a significant difference in patients with hematologic vs solid tumors and in those treated with B cell depletion vs other therapies. However, 16.0% (27/169) of patients had a subsequent positive test after a first negative result, with increased incidence in patients with hematologic malignancy (26.2%, 16/61) and stem cell/adoptive cell transplant (46.2%, 6/13). Conclusion(s): COVID- 19 is a significant barrier to oncologic care, and clearance times remain longer than reported for the general population. In this single center study, clearance time was > 1 month and further increased in patients with hematologic malignancy or on B cell depleting therapy. While adjusting clearance criteria to a single negative test or specific timeframe may be an attractive option to reduce delays, a large proportion of patients may have further positive PCR testing.
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Background: Management of acute respiratory distress in patients with COVID-19 has changed over the course of the pandemic. The impact of length of time on High Flow Nasal Cannula (HFNC) prior to mechanical ventilation is unknown. Methods: This is a multi-center retrospective chart review of COVID-positive hospitalized patients, who received mechanical ventilation from March 2020- October 2021. The primary outcome variable was survival to discharge, variables collated included patient demographics, vital signs, comorbidities, including the Charlson comorbidity index (CCI), as well as critical care therapeutic and diagnostic interventions. Results: All COVID-19 positive patients, with respiratory failure who underwent mechanical ventilation across study sites were included (N=709), of which 318 (45%) were accrued in March-May 2020. Patients had an average age of 62 (SD=15) years, majority male (67%), and an average CCI of 3.65 (SD=3.11). The unadjusted mortality for mechanically ventilated patients in our cohort was 56% (n=397). 169 (54%) of the remaining 312 were discharged home. Mortality varied over the study period, with the highest noted Nov 1st 2020 - Jan.31st 2021 (N=141, 69.8%) compared to other time periods (47-53%, p<0.0001). Notably at this time patients had the longest duration of pre-intubation high-flow oxygen support (mean 6.3 days vs. 4.2 days overall), the highest rate of Non-Invasiave Positive Pressure Ventilation (NIPPV) utilization (49% vs. 33% overall) and the lowest PaO2 to FiO2 ratio (mean 125 vs. 139 overall) (p<0.01). Duration of HFNC was independently associated with a higher risk of post-intubation mortality: OR (95% CI) = 3.1 (1.8-5.4) for 3-7 days, 7.2 (3.8-13.7) for ≥8 days (reference: 1-2 days) (p<0.0001) (accounting for age, gender, BMI and CCI). Furthermore, the magnitude of this association was found to vary between age groups: for 3-7 days duration (ref: 1-2 days), OR = 4.8 (1.9 - 12.1) in ≥65 years old vs. 2.1 (1.0 - 4.6) in <65 years old. Notably, at 8 days or more of HFNC, the association with age was reversed for ≥8 days duration (ref: 1-2 days): OR = 5.3 (2.0 - 13.9) in ≥65 years old vs. 8.6 (3.7 - 20.0) for <65 years old. Conclusion: The prolonged use of high flow oxygenation prior to mechanical intubation increased the risk of mortality, particularly in young patients use of HFNC for 8 days or more was associated with significantly higher mortality.
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Objective: This study investigates the effects of COVID-19 on brain microstructure among those recently recovering from COVID-19 through self isolation. Background: Microstructural differences have previously been detected in comparisons of COVID-19 patients with controls, particularly in regions related to the olfactory system. The olfactory system is connected with the caudate, putamen, thalamus, precuneus, and cingulate regions. Design/Methods: Here we report diffusion magnetic resonance imaging (3 T Siemens MRI) findings from 40 patients (mean age: 43.7, 68% female) who self-isolated after testing positive for COVID (COV+), and 14 COVID negative (COV-) subjects (mean age: 43, 64% female) who had flu-like symptoms. This is part of the Canadian-based NeuroCOVID-19 study. Fractional anisotropy (FA), mean diffusivity (MD), mode of anisotropy (MO), free water fraction (F), tissue-specific FA (FAt) and tissue-specific MD (MDt) were obtained using data with b=700 and 1400 (DIPY free-water model). Regions of interest in the grey matter and white matter were delineated using FreeSurfer. Differences between groups were assessed using an analysis of variance (ANOVA), the Kruskal-Wallis Test and the Mann-Whitney Test, corrected for false-discovery rate of 0.05. Effect size (Cohen's d) was also computed (d>0.45 deemed large effect). Results: In the COV+ group, all three tests revealed decreased FA and FAt in the insula, and increased MD in the parstriangularis cortex. Increased FA and FAt in the cuneus (along with decreased MD) was also found. MD was reduced in COV+ in the temporal and supramarginal areas. MO was lower in COV+ in the insula and amygdala regions. Conclusions: In patients, higher MD with lower FA and MO suggest increased extracellular fluids, while lower MD with decreased FA and MO may suggest necrotic debris built up following inflammation. The cuneus and insula are involved in visual and taste processing, respectively. This study highlights the need to study neurological effects of COVID-19.
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Objective: This study investigates the chronic effects of COVID-19 on brain microstructure. Background: Microstructural differences have previously been detected in comparisons of COVID-19 patients with controls, particularly in the insula, cuneus, inferior temporal and anterior cingulate regions. Design/Methods: Here we report diffusion magnetic resonance imaging (3 T Siemens MRI) findings from 20 participants (mean age: 45.3, 55% female), both immediately after recovery and at a 3-month follow-up. Fractional anisotropy (FA), mean diffusivity (MD), mode of diffusivity (MO), free water fraction (F), tissue-specific FA (FAt) and tissue-specific MD (MDt) were obtained using DTI data with b=700 and 1400 (DIPY free-water model). Regions of interest in the grey matter and white matter were delineated using FreeSurfer. To assess differences between baseline and follow-up, a paired t-test, the Wilcoxon Test and Friedman Test were performed, corrected for false-discovery rate of 0.05. Effect size (Cohen's d) was also computed (d>0.45 deemed large effect). Results: All three tests revealed decreased F in the hippocampus and decreased MD in the parahippocampal region of the WM at follow-up. In the GM, F was increased in the medial orbitofrontal region. In the WM, MD was increased in the paracentral region and MDt was increased in the parahippocampal and lateral orbitofrontal regions. Conclusions: These results suggest that microstructural abnormalities persist following recovery. Increased extracellular fluid (i.e. F and MD) in the frontal lobe suggest spreading of COVID-19 impact, while decreased F and MD in the hippocampal region suggest debris accumulation as part of the inflammatory process. None of the regions affected in sub-acute COVID-19 appear to fully recover within three months.
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Background: CLD patients may experience substantial burden and disruption of life associated with COVID-19 pandemic. The aim was to assess the impact of COVID-19 pandemic on CLD patients. Methods: CLD patients from our Global Liver and Global NASH Registries (GLR/GNR) were invited to complete a COVID-19 survey with 23 items starting March 2020. Questions included whether patients had been infected with COVID-19, characteristics of the illness for those who had been infected, and various aspects of pandemicrelated disruptions of life regardless of being diagnosed with COVID-19. Results: Out of 10,500 GLR/GNR enrollees, 2500 from 7 countries completed the survey: 20% chronic hepatitis B (CHB), 14% chronic hepatitis C (CHC), and 66% non-alcoholic fatty liver disease (NAFLD), mean (SD) age 49±13 years, 53% male. Of all survey completers, 9.3% had had COVID-19. Of those infected, 86% were diagnosed by laboratory test, 93% had least one symptom, 75% received treatment for their symptoms. The mean duration of illness was 12.5±10.5 days, 64% reported receiving antiviral treatment, 19% were hospitalized, 13% needed oxygen support, no one required mechanical ventilation. Of patients regardless of COVID-19 diagnosis, 11.3% reported that the pandemic had an impact on their liver disease with 73% reporting delays in follow-up care. The Life Disruption Event Perception (LDEP) questionnaire confirmed that 81% of COVID-19-infected patients vs. 69% patients without COVID-19 (p=0.0001) experienced worsening in at least one aspect of their life (Figure). Self-assessed health scores were lower in patients with COVID-19: 6.7±2.2 vs. 7.4±2.2 (on a 1-10 scale with 10 indicating perfect health) (p<0.0001) despite having reported similar scores before the pandemic (8.5±1.4 vs. 8.4±1.6, p=0.59). The highest proportion of exercise and social impairments were reported from Turkey and Mexico, respectively. In multivariate analysis, after adjustment for country of enrollment, liver disease etiology and severity, age, sex, BMI, diabetes, history of psychiatric comorbidities, having had COVID-19 was found to be independently associated with lower self-assessed health scores (β=-0.71±0.14, p<0.0001). Conclusion: CLD patients experience substantial burden of COVID-19 pandemic on their daily lives regardless of whether they had been infected. However, self-reported health scores were lower in CLD patients with COVID-19 infection in comparison to those who did not have it.
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Health care workers (HCWs) are at higher risk for SARS-CoV-2 infection and may play a role in transmitting the infection to vulnerable patients and members of the community. This is particularly worrisome in the context of asymptomatic infection. We performed a cross-sectional study looking at asymptomatic SARS-CoV-2 infection in HCWs. We screened asymptomatic HCWs for SARS-CoV-2 via PCR. Complementary viral genome sequencing was performed on positive swab specimens. A seroprevalence analysis was also performed using multiple assays. Asymptomatic health care worker cohorts had a combined swab positivity rate of 29/5776 (0.50%, 95%CI 0.32-0.75) relative to a comparative cohort of symptomatic HCWs, where 54/1597 (3.4%) tested positive for SARS-CoV-2 (ratio of symptomatic to asymptomatic 6.8:1). SARS-CoV-2 seroprevalence among 996 asymptomatic HCWs with no prior known exposure to SARS-CoV-2 was 1.4-3.4%, depending on assay. A novel in-house Coronavirus protein microarray showed differing SARS-CoV-2 protein reactivities and helped define likely true positives vs. suspected false positives. Our study demonstrates the utility of routine screening of asymptomatic HCWs, which may help to identify a significant proportion of infections.
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AimsBrief measurements of the subjective experience of stress with good predictive capability are important in a range of community mental health and research settings. The potential for large-scale implementation of such a measure for screening may facilitate early risk detection and intervention opportunities. Few such measures however have been developed and validated in epidemiological and longitudinal community samples. We designed a new single-item measure of the subjective level of stress (SLS-1) and tested its validity and ability to predict long-term mental health outcomes of up to 12 months through two separate studies.MethodsWe first examined the content and face validity of the SLS-1 with a panel consisting of mental health experts and laypersons. Two studies were conducted to examine its validity and predictive utility. In study 1, we tested the convergent and divergent validity as well as incremental validity of the SLS-1 in a large epidemiological sample of young people in Hong Kong (n = 1445). In study 2, in a consecutively recruited longitudinal community sample of young people (n = 258), we first performed the same procedures as in study 1 to ensure replicability of the findings. We then examined in this longitudinal sample the utility of the SLS-1 in predicting long-term depressive, anxiety and stress outcomes assessed at 3 months and 6 months (n = 182) and at 12 months (n = 84).ResultsThe SLS-1 demonstrated good content and face validity. Findings from the two studies showed that SLS-1 was moderately to strongly correlated with a range of mental health outcomes, including depressive, anxiety, stress and distress symptoms. We also demonstrated its ability to explain the variance explained in symptoms beyond other known personal and psychological factors. Using the longitudinal sample in study 2, we further showed the significant predictive capability of the SLS-1 for long-term symptom outcomes for up to 12 months even when accounting for demographic characteristics.ConclusionsThe findings altogether support the validity and predictive utility of the SLS-1 as a brief measure of stress with strong indications of both concurrent and long-term mental health outcomes. Given the value of brief measures of mental health risks at a population level, the SLS-1 may have potential for use as an early screening tool to inform early preventative intervention work.
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Objective. To assess the practice and technique of using a protective mask (surgical mask) in older adults. Methods: A convenience sample of 287 older adults aged >65 years were recruited between January and February 2017 when there was no respiratory epidemic. Their practice and technique of using a mask were assessed using a questionnaire and an observational checklist, respectively. Results: Older adults' practice and technique of using a mask were unsatisfactory. 30.1% and 26.9% indicated that they never wear a mask when taking care of family members with fever and respiratory infection, respectively. None could correctly perform all 12 steps in wearing and taking off a mask. 92.3%, 96.6%, and 93.7% did not perform hand hygiene before wearing and taking off the mask and after disposing of the mask, respectively. Conclusion: Compliance of older adults with wearing masks during a non-epidemic period was low. The commonly omitted steps of wearing and taking off a mask were related to hand hygiene. We recommend using the knowledge-attitude-practice model to rectify misconceptions and strengthen awareness on the use of masks in the required situations and on commonly omitted or incorrectly performed techniques.
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BACKGROUND: The spread of SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19), has been characterized as a worldwide pandemic. Currently, there are few preclinical animal models that suitably represent infection, as the main point of entry to human cells is via human angiotensin-converting enzyme 2 (ACE2) which is not present in typical preclinical mouse strains. Additionally, SARS-CoV-2 is highly virulent and unsafe for use in many research facilities. Here we describe the development of a preclinical animal model using intranasal administration of ACE2 followed by non-infectious SARS-CoV-2 pseudovirus (PsV) challenge. METHODS: To specifically generate our SARS-CoV-2 PsV, we used a lentivirus system. Following co-transfection with a packaging plasmid containing HIV Gag and Pol, luciferase-expressing lentiviruses, and a plasmid carrying the SARS-CoV-2 spike protein, SARS-CoV-2 PsVs can be isolated and purified. To better understand and maximize the infectivity of SARS-CoV-2 PsV, we generated PsV carrying spike protein variants known to have varying human ACE2 binding properties, including 19 deletion (19del) and 19del + D614G. RESULTS: Our system demonstrated the ability of PsVs to infect the respiratory passage of mice following intranasal hACE2 transduction. Additionally, we demonstrate in vitro and in vivo manipulability of our system using recombinant receptor-binding domain protein to prevent PsV infection. CONCLUSIONS: Our PsV system is able to model SARS-CoV-2 infections in a preclinical mouse model and can be used to test interventions or preventative treatments. We believe that this method can be extended to work in various mouse strains or to model infection with different coronaviruses. A simple in vivo system such as our model is crucial for rapidly and effectively responding to the current COVID-19 pandemic in addition to preparing for future potential coronavirus outbreaks.