The Effects of COVID-19 School Closures on Physical Fitness in Adolescents

Purpose: This study examined differences in measures of health-related physical fitness in adolescents before and after extended school closures due to COVID-19. Method: The sample consisted of 298 students (135 males and 163 females) from a laboratory high school. Data were collected through FITNESSGRAM assessments. A repeated-measures multivariate analysis of covariance was calculated to analyze differences in fitness before and after COVID-19 closures, including McNemar-Bowker and McNemar tests. Results: Statistically significant differences were identified for Progressive Aerobic Capacity Endurance Run (-4.2%;1.8 mlmiddotkg(-1)middotmin(-1)) and curl-up (-12.5%;7.9 repetitions). In addition, 18.8% fewer students were classified within the Healthy Fitness Zone for Progressive Aerobic Capacity Endurance Run, 4% for curl-up, 10.8% for push-up, and 6.4% for sit and reach. Conclusion: Results of this study demonstrate that there was a significant decline in physical fitness for secondary students during extended school closures and social isolation as a result of COVID-19.

Quantifying the reduction of airborne infectious viral load using a ventilated patient hood.

BACKGROUND: Healthcare workers treating SARS-CoV-2 patients are at risk of infection by respiratory exposure to patient-emitted, virus-laden aerosols. Source control devices such as ventilated patient isolation hoods have been shown to limit the dissemination of non-infectious airborne particles in laboratory tests, but data on their performance in mitigating the airborne transmission risk of infectious viruses are lacking. AIM: We used an infectious airborne virus to quantify the ability of a ventilated hood to reduce infectious virus exposure in indoor environments. METHODS: We nebulized 109 plaque forming units (pfu) of bacteriophage PhiX174 virus into a ∼30-m3 room when the hood was active or inactive. The airborne concentration of infectious virus was measured by BioSpot-VIVAS and settle plates using plaque assay quantification on the bacterial host Escherichia coli C. The airborne particle number concentration (PNC) was also monitored continuously using an optical particle sizer. FINDINGS: The median airborne viral concentration in the room reached 1.41 × 105 pfu/m3 with the hood inactive. When active, the hood reduced infectious virus concentration in air samples by 374-fold. The deposition of infectious virus on the surface of settle plates was reduced by 87-fold. This was associated with a 109-fold reduction in total airborne particle number escape rate. CONCLUSION: A personal ventilation hood significantly reduced airborne particle escape, considerably lowering infectious virus contamination in an indoor environment. Our findings support the further development of source control devices to mitigate nosocomial infection risk among healthcare workers exposed to airborne viruses in clinical settings.

Commentary: Pharmacologic Correlates that Address the Clinicopathobiology of COVID-19

COVID-19 could remain a pandemic until we get a SARS-CoV-2 vaccine to immunize the world population. In the interim, we have the opportunity to consider its clinicopathobiology in the context of the pharmacologic correlates available from the existing medical literature to prevent the COVID-19 infected patient from progressing into a fatal stage. This commentary serves as a forum for that end and suggests relatively non-toxic therapies that could be applied in a combinatorial fashion for consideration by the physicians and their patients with COVID-19 infection.Copyright © 2020 by the Association of Clinical Scientists, Inc.

Infection with Covid Variants of Concern in a Lung Transplant Population

The COVID pandemic has evolved as the SARS-2 Coronavirus (CoV-2) mutated into unique variants of concern (VOC). The clinical approach to COVID has evolved as new therapeutics have become available. Previous reports demonstrate differences in patient outcomes based on VOC, however outcomes in a lung transplant population have not been described. Our lung transplant program follows over 300 transplant recipients. Relevant information including date of first positive test, hospital admission, monoclonal antibody (mAb) or oral anti-viral treatment, CoV-2 vaccination history, tixagevimab/cilgavimab (T/C) and COVID attributed mortality have been tracked for quality improvement purposes. Outcomes were stratified by predominant US VOC at time of positive testing: wild strain 02/2020-02/2021, alpha strain 02/2021-05/2021, delta strain 06/2021-12/2021, omicron strain 01/2022- 09/25/2022. From 03/20/2020 through 09/25/2022, 142 recipients were diagnosed with COVID 152 times, including 9 recipients infected twice and 1 recipient infected 3 times. Most infected recipients tested positive with CoV-2 during the omicron wave. All recurrent infections occurred during the omicron wave. 8 deaths (5.6%) were attributed to COVID: 6 due to COVID respiratory failure, 1 stroke and 1 new restrictive-chronic lung allograft dysfunction. Therapies directed against CoV-2 were more likely administered in delta and omicron waves. Recipients were more likely to require hospital admission in wild type and alpha waves of CoV-2. Most deaths occurred in the wild type and delta waves. Deceased recipients, and those requiring hospital admission received less vaccinations and were less likely to have received T/C. (Table) This analysis shows changing trends in management and outcomes over the COVID pandemic. Future research should focus on transplant specific outcomes, including post-infection changes in allograft function and risk of developing chronic lung allograft dysfunction based on likely infecting VOC. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Morphoproteomic Features of Pulmonary Influenza A (H1N1) with Therapeutic Implications: A Case Study

Objective. Influenza pandemic of the human lung was caused by the Influenza A (H1N1) over 100 years ago in 1918, but it recurred in pandemic fashion in 2009. Understanding the pathobiology of this infectious agent in the human lung could lead to adjuvant therapies that are relatively non-toxic and reduce the mortality of the human host. Overall, our objective was to apply morphoproteomics to pulmo-nary lung sections from an autopsied victim so that we may better define its biology from the perspective of its interaction with the host and provide options for therapeutic targets. Methods. Morphoproteomic analysis from a case study of this Influenza A (H1N1) pulmonary infection included immunohistochemical probes to detect the expressions of fatty acid synthase (FAS), CD163+ (M2 polarized monocytes/macro-phages), and programmed death-ligand 1 (PD-L1) expression as part of the host response to interaction with the Influenza A (H1N1) virus.Results. Representative sections of the Influenza A (H1N1) victim's lung showed: cytoplasmic expression of FAS in most of the sloughed and atypical alveolar pneumocytes;abundance of intra-alveolar and alveolar interstitial CD163+ macrophages/monocytes;and PD-L1 expres-sion on occasional macrophages, and focally on collections of alveolar pneumocytes and the alveolar inter-stitium.Conclusion. Morphoproteomics and microanatomical features coincide with the etiopathogenic features of pulmonary Influenza A (H1N1) infection and the host response. This plus data mining of the medical literature suggests that adjunctive, targeted therapy such as metformin and vitamin D3 could ad-dress the biology of Influenza A (H1N1) pneumonia, enhance the host immune response, and prevent its progression to a life-threatening, ventilator-dependent clinical situation.

Disability, Food Insecurity, and Nutritional Assistance in the Context of COVID-19 Pandemic: Interrogating the Role of Perceived Everyday Discrimination

The COVID-19 pandemic has amplified the need for nutritional assistance among many households, but prior research suggests that people with disabilities and other marginalized groups have been less likely to seek needed assistance due to perceived discriminatory experiences. We examined variation in the use of food assistance programs during the pandemic using data from a community survey of working-age adults with a sizeable subsample of people with disabilities in the Intermountain West region of the United States (N = 1,745). Study findings revealed that having a self-reported disability was associated with greater participation in food assistance programs, which was driven by higher rates of food insecurity. However, the mediated association between disability and nutritional assistance was reduced for food insecure adults who reported greater experiences of perceived daily discrimination. The implication is that perceived discriminatory experiences have diminished the benefits of health-promoting social services during the pandemic. Ways in which the findings extend previous literature on disability, social marginalization, and health disparities is also discussed.

Nutritional status and COVID-19 in children: a Caribbean inpatient survey

Objective: The objectives are to determine the incidence of malnutrition and anemia and evaluate the association of nutritional status and COVID-19-related clinical outcomes in children hospitalized for COVID-19. Method(s): This multi-island inpatient survey presents data from nine hospitals in three Caribbean islands in children from birth to 17 years from September 2020 to July 2021. We explore statistical associations with inpatient characteristics and potential differences between malnourished and well-nourished children. Result(s): Among children hospitalized for COVID-19, 6.8% were stunted, 6.6% were underweight, 13.6% were overweight/ obese, and 30% had anemia. Anemia was associated with multi-system inflammatory syndrome (MIS-C) in children but not with malnutrition. The prevalence of underweight children exceeded the 4.4% prevalence in the general pediatric population in islands and there was a greater-than-expected prevalence of overweight children hospitalized with COVID-19. No clear associations were detected between malnutrition and indicator outcomes. There were two deaths in children with severe malnutrition, COVID and septicemia identified after the study window. Conclusion(s): Hospitalizations exceeded baseline population rates of undernutrition but no significant associations were detected possibly due to small numbers. T cell activity is associated with less disease severity in SARS-CoV-2 infection and the diverse repertoire of naive T lymphocytes in children may confer protection to undernourished children. The deaths in two children with severe malnutrition and sepsis may suggest a compound effect on immunity by nutrition severity and COVID-19 disease. Overweight children in this cohort may reflect an increased prevalence of overweight children in the general population that requires further evaluation and intervention.

Early Clinical Experience with Nirmatrelvir/Ritonavir for Treatment of COVID-19 in Solid Organ Transplant Recipients

Purpose: Nirmatrelvir/ritonavir use has not yet been described in solid organ transplant recipients (SOTR) who become infected with COVID-19. The objective of our study was to evaluate outcomes among a heterogeneous population of SOTR and quantify the drug-drug interaction with commonly used immunosuppressive medications. Method(s): This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor or mammalian target of rapamycin inhibitor who were prescribed nirmatrelvir/ritonavir between 12/28/21 and 1/6/2022. Result(s): A total of 26 adult SOTR were included (n=20 tacrolimus, n=4 cyclosporine, n=3 everolimus, n=1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of nirmatrelvir/ritonavir: hold tacrolimus, reduce cyclosporine dose to 20% of baseline daily dose, and/or hold everolimus/sirolimus. Two patients (7.7%) were hospitalized;one patient for symptoms related to COVID-19 and the other for infectious diarrhea. No patients died within 12 days of receipt of nirmatrelvir/ritonavir. Median time to first CNI trough from completion of nirmatrelvir/ritonavir was 2 days (IQR, 1 - 3). Median tacrolimus trough concentration pre- and post-nirmatrelvir/ritonavir were 7.7 ng/mL (IQR, 6.6 - 8.6) and 5.3 ng/mL (IQR, 3.6 - 8.5), respectively. One patient on cyclosporine had trough concentrations pre- and post- nirmatrelvir/ritonavir of 73 ng/mL and 45 ng/ mL (day 9), while the other patient had a trough of 75.9 ng/mL prior and 190 ng/mL and 80 ng/mL on days 6 and 9, respectively. Median everolimus trough concentration prior to receipt of nirmatrelvir/ritonavir was 4.8 ng/mL (IQR, 3 - 4.9). Everolimus trough concentrations post-nirmatrelvir/ritonavir were undetectable in two patients on day 7 and day 9, and 1.4 ng/mL on day 8 in the third patient. Conclusion(s): Our results suggest that nirmatrelvir/ritonavir may be an effective therapy to prevent COVID-19-related hospitalization and death in SOTR. Furthermore, the clinically significant interaction between nirmatrelvir/ritonavir and immunosuppressive agents can be reasonably managed with a standardized dosing protocol.

ETAVOPIVAT TREATMENT FOR UP TO 12 WEEKS IN PATIENTS WITH SICKLE CELL DISEASE IS WELL TOLERATED AND IMPROVES RED BLOOD CELL HEALTH

Background: Etavopivat, an investigational, once-daily, selective, activator of erythrocyte pyruvate kinase (PKR) increases PKR activity, resulting in decreased 2,3-DPG and increased ATP in red blood cells (RBCs) of healthy volunteers and patients (pts) with sickle cell disease (SCD).1,2 Aims: We report results of an open-label (OL) extension cohort from a Phase 1 study (NCT03815695) designed to characterize the safety and clinical activity of etavopivat at a maximal pharmacodynamic dose in pts with SCD. Methods: 15 pts were enrolled to receive etavopivat 400 mg once daily for 12 wks, followed by a 4-wk follow-up. Assessments included safety, pharmacokinetics, pharmacodynamics, RBC health parameters and systemic markers of SCD pathophysiology. Results: Of 15 pts (age 32.3 ±10.1 yr;HbSS/SC n=13/2), 14 completed 12-wks of treatment (tx);1 pt discontinued tx after ∼2 wks. Etavopivat 400 mg once daily was generally well tolerated. Adverse events (AEs) reported during tx and follow-up were commonly low grade (Gr) and consistent with pts' SCD. Gr1-2 AEs in >2 pts (n [%]) were sickle cell pain events (9 [60%]);headache (5 [33%]);and upper respiratory tract infection (3 [20%]). The Gr3-4 AE in >1 pt was sickle cell vaso-occlusion (VOC;4 [27%]). On-tx serious adverse events (SAEs;1 pt each) were Gr3 VOC post Gr3 COVID (not tx-related) and Gr3 left femoral deep vein thrombosis (possibly related, resulting in tx discontinuation as stated above). SAEs (1 pt each) during the 4-wk follow-up were Gr3 acute chest syndrome + Gr3 VOC, Gr3 non-cardiac chest pain and Gr3 syncope (all unrelated). Observed increases in ATP and decreases in 2,3-DPG were durable over 12 wks of etavopivat tx. Etavopivat tx normalized hemoglobin (Hb)S-oxygen affinity to that of HbA. Etavopivat tx over 12 wks improved overall sickle RBC health, demonstrated by a reduction in point of sickling as well as improved measures of deformability and hydration of sickle RBCs (all P<0.01;Figure). Etavopivat tx over 12 wks was associated with a sustained significant increase in Hb compared with baseline (BL;P<0.0001), with mean maximal increase of 1.5 (range 0.7-2.3) g/dL. Ontx increase in Hb >1g/dL was achieved in 11 (73%) pts, for whom the mean maximal Hb increase was 1.8 (1.2-2.3) g/dL. Absolute reticulocytes, indirect bilirubin and lactate dehydrogenase significantly decreased from BL and were sustained over the 12wk period (all P<0.05), indicative of increased RBC lifespan and decreased hemolysis. Several markers of disease activity significantly decreased from BL during daily etavopivat tx, including the inflammatory marker tumor necrosis factor-α , which decreased by 35% (P<0.001). Based on preliminary exploratory analysis with an aggregate duration of etavopivat exposure of 3.32 pt-yrs in the OL cohort, a decrease in the trend for VOC Hospitalizations was observed: annualized historical and on-tx VOC Hospitalization rates were 0.93 and 0.30, respectively;the 1 on-tx VOC Hospitalization was COVID-related. Summary/Conclusion: Etavopivat 400 mg once daily for up to 12 wks demonstrated a tolerable safety profile and showed improvements in various markers of RBC health in pts with SCD. Rapid and sustained increases in Hb were associated with decreases in reticulocyte counts and markers of hemolysis, supporting increased sickle RBC lifespan and improved anemia. Together, these results support further evaluation of etavopivat in the Phase 2/3 Hibiscus Study (NCT04624659) currently enrolling pts. (Figure Presented).

Trans Mountain Corporation Overcomes Numerous Challenges to Construct the Trans Mountain Expansion Project

The Trans Mountain Pipeline Expansion Project is the most largest technically challenging pipeline project ever constructed in Canada and possibly in North America. This project consists of 987 km (613 mi) of NPS 36 and NPS 42 pipeline, 11 pump stations, 3 berths, addition of 19 petroleum storage tanks, and elevation changes not normally designed for in liquid pipelines. The challenges are many and diverse. With similar challenging projects like Keystone XL being cancelled, Trans Mountain stands out in that this challenging project is under construction now with completion planned for late 2023. Challenges include environmental, regulatory, technical, geotechnical, geological, topographical, equipment, manpower, COVID-19, safety, schedule, public perception, design, and recent concerns in BC like fires, extreme temperatures, and overland flooding as well as others. Conceived by Kinder Morgan Corporation (KMC) as an expansion of its existing pipeline to expand offshore markets, ultimately the risk for the pipeline completion was such that KMC sold the pipeline to the Canadian government, essentially the people of Canada. It is very likely that once completed, Trans Mountain Corporation, the owners of the TMC system, will be sold to a major pipeline operator as the Canadian government is not in the pipeline operating business. This paper will outline where the project is now, how it got here, and how it managed all of the challenges faced. © 2022 ASCE.

Vasculitis: From Diagnosis to Treatment

Vasculitis refers to diseases that cause blood vessel walls to thicken and narrow, cutting off blood supply to tissues and organs. Vasculitis encapsulates several conditions, and the cause of vasculitis is often unknown. This book explores various forms of vasculitis and options for treatment. Chapter One includes a detailed description of giant cell arteritis, a form of vasculitis involving inflammation of the middle and large arteries, including the latest management strategies. Chapter Two concerns different types of vasculitis affecting the lungs, their signs and symptoms, treatment, and complications needed for diagnosis. Chapter Three deals with eosinophilic granulomatosis with polyangiitis, a multisystemic necrotizing vasculitis characterized by allergic rhinitis, asthma, and peripheral eosinophilia. Chapter Four describes the common pathophysiology and cardiovascular complications arising in different vasculidities. Chapter Five reviews the pathophysiology, epidemiology, diagnostic investigation, and treatment of infection etiologies of Herpesviridae associated with vasculitis. Chapter Six elucidates the impact of vasculitis on the gastrointestinal system. Chapter Seven explains hypocomplementic urticarial vasculitis syndrome, defined as presence of greater than six months of urticaria along with hypocomplementemia and multi-system manifestations such as recurrent abdominal pain, uveitis, arthralgia and glomerulonephritis. Chapter Eight explicates the use of biologics in treating rheumatology disorders, with rituximab being recommended in organ-threatening, refractory systemic lupus erythematosus. Lastly, Chapter Nine discusses the pathophysiology and adverse effects of adenoviral vector vaccinations for SARS-CoV-2 and the importance of identifying the true epidemiology of adverse outcomes regarding promoting increased acceptance of COVID-19 vaccinations, while stressing that despite the possibility of adverse outcomes, the benefits of vaccination outweigh the risks of remaining unvaccinated. © 2021 by Nova Science Publishers, Inc.

Metagenomics of Wastewater Influent from Wastewater Treatment Facilities across Ontario in the Era of Emerging SARS-CoV-2 Variants of Concern.

We report metagenomic sequencing analyses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in composite wastewater influent from 10 regions in Ontario, Canada, during the transition between Delta and Omicron variants of concern. The Delta and Omicron BA.1/BA.1.1 and BA.2-defining mutations occurring in various frequencies were reported in the consensus and subconsensus sequences of the composite samples.

Risk factors for SARS-CoV-2 seroprevalence following the first pandemic wave in UK healthcare workers in a large NHS Foundation Trust

Background: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity.

Impacts of COVID-19 lockdown on private domestic groundwater sample numbers, E. coli presence and E. coli concentration across Ontario, January 2020-March 2021: An interrupted time-series analysis.

Approximately 1.5 million individuals in Ontario are supplied by private water wells (private groundwater supplies). Unlike municipal supplies, private well water quality remains unregulated, with owners responsible for testing, treating, and maintaining their own water supplies. The COVID-19 global pandemic and associated non-pharmaceutical interventions (NPIs) have impacted many environmental (e.g., surface water and air quality) and human (e.g., healthcare, transportation) systems over the past 15-months (January 2020 to March 2021). To date, the impact of these interventions on private groundwater systems remains largely unknown. Accordingly, the current study aimed to investigate the impact of a province-wide COVID-19 lockdown (late-March 2020) on health behaviours (i.e., private domestic groundwater sampling) and groundwater quality (via Escherichia coli (E. coli) detection and concentration) in private well water in Ontario, using time-series analyses (seasonal decomposition, interrupted time-series) of a large-spatio-temporal dataset (January 2016 to March 2021; N = 743,200 samples). Findings indicate that lockdown concurred with an immediate (p = 0.015) and sustained (p < 0.001) decrease in sampling rates, equating to approximately 2200 fewer samples received per week post-interruption. Likewise, a slightly decreased E. coli detection rate was observed approximately one month after lockdowns began (p = 0.003), while the proportion of "highly contaminated" samples (i.e., E. coli > 10 CFU/100 mL) was shown to increase within one month (p = 0.02), followed by a sustained decrease for the remainder of the year (May 2020-December 2020). Analyses strongly suggest that COVID-19 interventions resulted in discernible impacts on both well user behaviours and hydrogeological mechanisms. Findings may be used as an evidence-base for assisting policy makers, public health practitioners and private well owners in developing recommendations and mitigation strategies to manage public health risks during extreme and/or unprecedented future events.