The impact of smoking status and smoking-related comorbidities on COVID-19 patient outcomes: A causal mediation analysis.

INTRODUCTION: Smoking history is a known risk factor for significant chronic diseases as well as pulmonary infections; however, the impact of smoking status on COVID-19 outcomes has not been conclusively characterized. This study aims to evaluate the association of smoking status on COVID-19 outcomes, and to explore the mechanism by which smoking and smoking-related comorbidities relate to COVID-19 outcomes. METHODS: Patients admitted with SARS-CoV-2 infection from November 2020 through January 2021 were included in this study. Causal mediation models investigating the associations between smoking status and the outcomes of mortality, intensive care unit (ICU) admission, advanced respiratory support, mechanical ventilation, ICU length of stay, and hospital length of stay, through mediation via smoking-related comorbidities, were examined. RESULTS: Active smokers did not experience worse COVID-19 outcomes once hospitalized. Former smokers had a higher odds of mortality (total effect OR 1.59, 95% CI 1.07-2.38, p=.01; indirect effect OR 1.45, 95% CI 1.09-1.93, p<.001), and advanced respiratory support (total effect OR 1.31, 95% CI 1.04-1.67, p=.02; indirect effect OR 1.26, 95% C1.03-1.54, p=.02), which were mediated by smoking-related comorbidities. While there was a non-significant increase in the total effect for mechanical ventilation, smoking-related comorbidities were significant mediators for their increased need (total effect OR 1.40, 95% CI 0.92-2.14, p=.13; indirect effect OR 1.47, 95% CI 1.10-1.87, p<.001). CONCLUSION: While active smokers did not experience worse COVID-19 outcomes compared to never smokers, these results should be interpreted with caution. Compared to never smokers, former smokers had greater odds of mortality, advanced respiratory support, and mechanical ventilation which was significantly mediated through smoking-related comorbidities. IMPLICATIONS: Previous studies have linked smoking status with worse COVID-19 outcomes, and have inferred that smoking-related comorbidities may play a role in these findings. This causal mediation analysis provides statistical evidence supporting this hypothesis, clarifying the risk that smoking-related comorbidities impart on COVID-19 outcomes in those with a smoking history.

Social and Demographic Disparities in the Severity of Multisystem Inflammatory Syndrome in Children.

Social constructs are known risk factors for multisystem inflammatory syndrome in children. A review of 206 patients demonstrated that children who were non-Hispanic Black, over the age of 12 years or living in a disadvantaged neighborhood associated with severe multisystem inflammatory syndrome in children (intensive care unit admission, intubation and/or vasopressor use).

Outcomes and antibiotic use in patients with coronavirus disease 2019 (COVID-19) admitted to an intensive care unit.

Antibiotic overuse is high in patients hospitalized with coronavirus disease 2019 (COVID-19) despite a low documented prevalence of bacterial infections in many studies. In this study evaluating 65 COVID-19 patients in the intensive care unit, empiric broad-spectrum antibiotics were often overutilized with an inertia to de-escalate despite negative culture results.

Serum biomarkers for prediction of mortality in patients with COVID-19.

BACKGROUND: There is limited information regarding the role of biomarker levels at predicting mortality in patients with the coronavirus disease (COVID-19) pandemic. The purpose of this study is to determine the differences in serum biomarker levels in adults with COVID-19 who survived hospitalization from those who did not. METHODS: A comprehensive search was completed on PubMed, EMBASE and Cochrane libraries to identify studies of interest. Endpoints of interest were blood counts, hepatic function test, acute phase reactants, cytokines and cardiac biomarkers. RESULTS: A total of 10 studies with 1584 patients were included in the pooled analyses. Biomarkers that were noted to be significantly higher in those who died from coronavirus disease included: white blood cell count, neutrophil count, C-reactive protein, high sensitivity C-reactive protein, procalcitonin, ferritin, D-dimer, interleukin-6, lactate dehydrogenase, creatine kinase, prothrombin time, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine. Lymphocyte count, platelet count and albumin were significantly lower in patients who died. CONCLUSION: This pooled analysis of 10 studies including 1584 patients identified significant differences in biomarkers on admission in patients who survived from those who did not. Further research is needed to develop risk stratification models to help with judicious use of limited health-care resources.

Disparities in case frequency and mortality of coronavirus disease 2019 (COVID-19) among various states in the United States.

OBJECTIVE: To utilize publicly reported, state-level data to identify factors associated with the frequency of cases, tests, and mortality in the USA. MATERIALS AND METHODS: Retrospective study using publicly reported data collected included the number of COVID-19 cases, tests and mortality from March 14th through April 30th. Publicly available state-level data was collected which included: demographics comorbidities, state characteristics and environmental factors. Univariate and multivariate regression analyses were performed to identify the significantly associated factors with percent mortality, case and testing frequency. All analyses were state-level analyses and not patient-level analyses. RESULTS: A total of 1,090,500 COVID-19 cases were reported during the study period. The calculated case and testing frequency were 3332 and 19,193 per 1,000,000 patients. There were 63,642 deaths during this period which resulted in a mortality of 5.8%. Factors including to but not limited to population density (beta coefficient 7.5, p < .01), transportation volume (beta coefficient 0.1, p < .01), tourism index (beta coefficient -0.1, p = .02) and older age (beta coefficient 0.2, p = .01) are associated with case frequency and percent mortality. CONCLUSIONS: There were wide variations in testing and case frequencies of COVID-19 among different states in the US. States with higher population density had a higher case and testing rate. States with larger population of elderly and higher tourism had a higher mortality. Key messages There were wide variations in testing and case frequencies of COVID-19 among different states in the USA. States with higher population density had a higher case and testing rate. States with larger population of elderly and higher tourism had a higher mortality.

The Unfamiliar Case of COVID-19 Induced Cerebral Venous Sinus Thrombosis in a Pediatric Patient.

The SARS-CoV-2 virus responsible for COVID-19 infection has affected the world from the end of 2019 with pulmonary and extrapulmonary manifestations. Hematologic complications are a rare but severe complication of the COVID-19 infection. There have been very few cases reported in the past showing thrombotic complications in the pediatric age group. We present a case of a 12-year-old male child showing cerebral venous sinus thrombosis (CVST) who tested positive for COVID-19 at the same time. We highlight the potential of this complication in the pediatric age group and discuss the treatment, which is an infrequent phenomenon.

COVID-19 patients with obesity at risk for worse outcomes despite younger age and fewer inflammatory derangements.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral pulmonary infection that can progress to cytokine storm syndrome because of widespread dysregulated inflammatory response. Many patients at risk for severe COVID-19 manifestation have been identified as those with preexisting conditions of pulmonary origin, as well as conditions that impair appropriate immune response, such as obesity. OBJECTIVES: The aim of this study is to describe the manifestation, clinical course, and inflammatory biomarker milieu of COVID-19 in patients with obesity. SETTING: University Hospital Philadelphia, Pennsylvania. METHODS: In this retrospective cohort study, 600 patients who were positive for COVID-19 were stratified by World Health Organization (WHO) obesity class and their presenting symptoms, disease biomarkers, demographics, and outcomes (intubation rate, intensive care unit [ICU] admission, length of stay [LOS], and mortality) were investigated. RESULTS: Age was inversely related to obesity class; patients of obesity class III presented 12.9 years younger than patients of normal weight (P < .0001). Initial ferritin lab values were negatively correlated with increasing obesity class (P = .0192). Normal or near-normal lymphocyte profile was noted in patients with obesity compared with patients without obesity (P = .0017). Patients with obesity had an increased rate of ICU admission (P = .0215) and increased length of stay (P = .0004), but no differences in intubation rate (P = .3705) or mortality (P = .2486). CONCLUSION: Patients with obesity were more likely to present to the hospital at a younger age, with reduced levels of COVID-19 related biomarker disturbances, and increased LOS and ICU admission rates, although were not at increased risk for mortality.

The effects of the COVID-19 pandemic on patients with obesity undergoing bariatric care.

BACKGROUND: Patients with obesity are at increased risk of developing severe COVID-19. The pandemic has caused delays in preoperative preparation, progression, and completion of bariatric surgeries. OBJECTIVES: The aim of this study was to evaluate the impact of COVID-19 restrictions on bariatric surgery patients and assess their concern of COVID-19 as they continue the preoperative process. SETTING: Philadelphia, Pennsylvania METHODS: A questionnaire was administered to patients to assess the impact of COVID-19 on their weight loss goals, physical activity, and diet. Time points assessed were initial bariatric consultation (T1), as well as the beginning (T2), and the end (T3) of lockdown restrictions in the region. RESULTS: Seventy-four participants were invited and 50 completed the survey, for a response rate of 67.6%. The average age of participants was 44.1 years. Two-thirds of patients reported significant concern that COVID-19 would affect their weight loss goals. Patients reported significant improvements in their diet from T1 to T2 (P < .01). However, at T3, some patients returned to behaviors held at T1, with snacking behaviors significantly increasing between T2 and T3 (P < .01). Physical activity decreased in 60% of patients between T2 to T3. The vast majority (90%) wanted to have their surgery as soon as possible; 56% reported low levels of concern for COVID-19 infection. CONCLUSION: Bariatric patients were highly motivated to proceed with bariatric surgery despite the risks imposed by the pandemic.

Covid-19 in an infant with systemic to pulmonary artery shunt dependent functionally univentricular physiology.

We report a case of two-month old with a functionally univentricular heart and parallel circulation who presented to the emergency department with Covid-19 and subsequently developed acute respiratory distress syndrome. The course of illness, clinical values, and laboratory markers are characterized in this report.

Pediatric Intensive Care Unit Admissions for COVID-19: Insights Using State-Level Data.

INTRODUCTION: Intensive care has played a pivotal role during the COVID-19 pandemic as many patients developed severe pulmonary complications. The availability of information in pediatric intensive care units (PICUs) remains limited. The purpose of this study is to characterize COVID-19 positive admissions (CPAs) in the United States and to determine factors that may impact those admissions. MATERIALS AND METHODS: This is a retrospective cohort study using data from the COVID-19 Virtual Pediatric System (VPS) dashboard containing information regarding respiratory support and comorbidities for all CPAs between March and April 2020. The state-level data contained 13 different factors from population density, comorbid conditions, and social distancing score. The absolute CPA count was converted to frequency using the state's population. Univariate and multivariate regression analyses were performed to assess the association between CPA frequency and admission endpoints. RESULTS: A total of 205 CPAs were reported by 167 PICUs across 48 states. The estimated CPA frequency was 2.8 per million children in a one-month period. A total of 3,235 tests were conducted of which 6.3% were positive. Children above 11 years of age comprised 69.7% of the total cohort and 35.1% had moderated or severe comorbidities. The median duration of a CPA was 4.9 days (1.25-12.00 days). Out of the 1,132 total CPA days, 592 (52.2%) involved mechanical ventilation. The inpatient mortalities were 3 (1.4%). Multivariate analyses demonstrated an association between CPAs with greater population density (beta coefficient 0.01, p < 0.01). Multivariate analyses also demonstrated an association between pediatric type 1 diabetes mellitus with increased CPA duration requiring advanced respiratory support (beta coefficient 5.1, p < 0.01) and intubation (beta coefficient 4.6, p < 0.01). CONCLUSIONS: Inpatient mortality during PICU CPAs is relatively low at 1.4%. CPA frequency seems to be impacted by population density. Type 1 DM appears to be associated with increased duration of HFNC and intubation. These factors should be included in future studies using patient-level data.

Factors associated with deep venous thrombosis in patients infected with coronavirus disease 2019: a meta-analysis.

Coronavirus disease 2019 (COVID-19) has affected more than 6 million patients worldwide. Deep venous thrombosis (DVT) has been increasingly recognized complication in these patients and is associated with increased morbidity and mortality. However, the factors associated with development of DVT in patients with COVID-19 have not been elucidated due to the novelty of the virus. We performed a meta-analysis of published studies comparing laboratory results in COVID-19 patients with and without DVT with the aim of identifying risk factors. We searched major databases for studies evaluating DVT in COVID-positive patients and performed a meta-analysis of baseline laboratory markers associated with development of DVT. A total of six studies with 678 patients were included in the pooled analyses. Of the 678 patients, 205 of patients had a DVT. Patients diagnosed with DVT were more likely to be older [mean difference 4.59 years, 95% confidence interval (CI) 1.25-7.92], and needing admission to ICU (relative risk 1.96, 95% CI 1.09-3.51). Patients with DVT had significantly higher white cell count (mean difference 1.36 × 109/l, 95% CI 0.33-2.40) and d-dimer levels (mean difference 3229.8, 95% CI 1501.5-4958.1). Lymphocyte count was lower in patients with DVT (mean difference -0.19 × 109/l, 95% CI -0.37 to -0.02). Patients with COVID-19 who develop DVT are more likely to be older and have leukocytosis with lymphopenia. Moreover, d-dimer is statistically higher and patients that are admitted to the ICU are at great risk to develop DVT.

COVID-19 and Hyperinflammatory Syndrome in Children: Kawasaki Disease with Macrophage Activation Syndrome in Disguise?

A hyperinflammatory syndrome has been described in times of COVID-19 in children. In the setting of uncertainty due to a new virus, the so-called hyperinflammatory syndrome has been coined as a novel entity by some and is being referred to as pediatric inflammatory multisystem syndrome (PIMS). However, the characteristics of the syndrome resemble those of Kawasaki disease (KD), an inflammatory syndrome in children that can lead to coronary artery abnormalities due to a subsequent vasculitis. Furthermore, Kawasaki disease may occasionally trigger macrophage activation syndrome (MAS), a condition in which there is uncontrolled activation and proliferation of macrophages and other cell types, and could lead to multiorgan system dysfunction. This study provides a review of the data regarding COVID-19, Kawasaki disease, and macrophage activation syndrome to demonstrate the similarities and differences between the inflammatory syndrome seen with COVID-19 and KD. In addition, a framework for diagnosis and evaluation is provided that focuses on the pathway previously established for KD and MAS. The authors believe that based on current knowledge, KD treatment delays may carry deleterious effects in the near future for children with COVID-19-related Kawasaki disease.

Disparities in Case Frequency and Mortality of Coronavirus Disease 2019 (COVID-19) Among Various States in the United States (preprint)

Objective: To utilize publicly reported, state-level data to identify factors associated with the frequency of cases, tests, and mortality in the US. Materials & Methods: Retrospective study using publicly reported data collected included the number of COVID-19 cases, tests, and mortality from March 14th through April 30th, 2020. Publicly available state-level data was collected which included: demographics comorbidities, state characteristics and environmental factors. Univariate and multivariate regression analyses were performed to identify the significantly associated factors with percent mortality, case and testing frequency. All analyses were state-level analyses and not patient-level analyses. Results: A total of 1,090,500 COVID-19 cases were reported during the study period. The calculated case and testing frequency were 3,332 and 19,193 per 1,000,000 patients. There were 63,642 deaths during this period which resulted in a mortality of 5.8%. Factors including to but not limited to population density (beta coefficient 7.5, p< 0.01), transportation volume (beta coefficient 0.1, p< 0.01), tourism index (beta coefficient -0.1, p=0.02) and older age (beta coefficient 0.2, p=0.01) are associated with case frequency and percent mortality. Conclusions: There were wide variations in testing and case frequencies of COVID-19 among different states in the US. States with higher population density had a higher case and testing rate. States with larger population of elderly and higher tourism had a higher mortality.

Pediatric intensive care unit admissions for COVID-19: insights using state level data (preprint)

Introduction Intensive care has played a pivotal role during the COVID-19 pandemic as many patients developed severe pulmonary complications. The availability of information in pediatric intensive care (PICUs) remains limited. The purpose of this study is to characterize COVID-19 positive admissions (CPAs) in the United States and to determine factors that may impact those admissions. Materials and Methods This is a retrospective cohort study using data from the COVID-19 dashboard virtual pediatric system containing information regarding respiratory support and comorbidities for all CPAs between March and April 2020. The state level data contained 13 different factors from population density, comorbid conditions and social distancing score. The absolute CPAs count was converted to frequency using the state's population. Univariate and multivariate regression analyses were performed to assess the association between CPAs frequency and endpoints. Results A total of 205 CPAs were reported by 167 PICUs across 48 states. The estimated CPAs frequency was 2.8 per million children. A total of 3,235 tests were conducted with 6.3% positive tests. Children above 11 years of age comprised 69.7% of the total cohort and 35.1% had moderated or severe comorbidities. The median duration of a CPA was 4.9 days [1.25-12.00 days]. Out of the 1,132 total CPA days, 592 [52.2%] were for mechanical ventilation. The inpatient mortalities were 3 [1.4%]. Multivariate analyses demonstrated an association between CPA's with greater population density [beta-coefficient 0.01, p<0.01] and increased percent of children receiving the influenza vaccination [beta-coefficient 0.17, p=0.01]. Conclusions Inpatient mortality during PICU CPAs is relatively low at 1.4%. CPA frequency seems to be impacted by population density while characteristics of illness severity appear to be associated with ultraviolet index, temperature, and comorbidities such as Type 1 diabetes. These factors should be included in future studies using patient-level data.

Heart University: a new online educational forum in paediatric and adult congenital cardiac care. The future of virtual learning in a post-pandemic world?

Online learning has become an increasingly expected and popular component for education of the modern-day adult learner, including the medical provider. In light of the recent coronavirus pandemic, there has never been more urgency to establish opportunities for supplemental online learning. Heart University aims to be "the go-to online resource" for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of paedagogical material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practising provider. In this manuscript, we review the aims, development, current offerings and standing, and future goals of Heart University.