Introduction: E-cigarette, or vaping, product use-associated lung injury (EVALI) results from inhaling the aerosol of e-cigarettes and has similar clinical features to coronavirus disease 2019 (COVID-19). EVALI case counts since the declaration of the COVID-19 pandemic is unknown. Methods: A retrospective electronic health record chart review of adolescents hospitalized at one institution with EVALI was conducted. Clinical characteristics and hospital course of patients hospitalized during the pandemic were compared to those pre-pandemic. Results: The clinical presentation of adolescents hospitalized prior-to (n=19) and during the COVID-19 pandemic (n=22) were similar with respect to constitutional, respiratory, and gastrointestinal symptoms. All patients hospitalized during the pandemic were tested for COVID-19 at least once. Only one patient had a positive SARS-CoV-2 RT-PCR test result. 31 out of 39 patients treated with corticosteroids had clinical improvement within 24 hours (79%). Patients hospitalized during the pandemic had a shorter median length of stay (5 vs 7 days, p<0.01), and were less often discharged with home oxygen (1 vs 6 patients, p=0.04). Pulmonary function tests improved pre-to post-corticosteroid treatment and post-corticosteroid to follow-up. Conclusions: Eliciting a history of vaping in adolescents presenting with constitutional, respiratory, and gastrointestinal symptoms is important to identify EVALI cases, which have continued throughout the COVID-19 pandemic. A shorter length of stay with less need for mechanical ventilation and home oxygen in adolescents hospitalized during the pandemic may reflect increased familiarity with EVALI characteristics. Corticosteroids led to clinical and pulmonary function improvement.

Background and Aims: Worldwide, the incidence of COVID-19 is lower in children than in adults and symptoms are less severe. So far, few studies from Latin America have been published on the behavior of COVID-19 in children with cancer. Purpose: To characterize the epidemiology, clinical course, morbidity, and mortality in children with cancer and COVID-19. Methods: All patients registered in the Argentine National Pediatric Cancer Registry (ROHA) with diagnosis of SARS-CoV-2 between December 4, 2020, and May 3, 2022 were included. Variables analyzed were: sex, age at COVID-19 diagnosis, clinical presentation at diagnosis, symptom severity, tumor type, intensive care requirement, specific treatment for COVID-19, vital status, and cause of death. Mortality was analyzed comparing the three main waves. Results: Overall, 888 children with cancer and COVID-19 infection were registered (484 females); 437 (49.2%) had leukemia, followed by central nervous system tumors (CNS-T) 120 (13.5%). Of the children, 57.2% (n=508) were symptomatic; 75% were febrile, and 37% (n=210) had neutropenia; 17.1% (n=152) were diagnosed within one month of cancer diagnosis. A total of 154 children had severe or critical symptoms (17%). In this study, 112 deaths were reported, 105 (94%) due to disease progression, sepsis, comorbidities, or treatment complications. Seven patients (0.8%) died from COVID-19, all diagnosed with leukemia/lymphoma. No association of deaths was found between the three waves analyzed. Conclusions: Based on the ROHA data, we may conclude that in pediatric cancer patients, contrary to what was initially expected, morbidity and mortality due to COVID-19 were not increased.

Purpose: Left ventricular diastolic dysfunction (LVDD) is associated with poor outcomes in intensive care unit (ICU). Nonetheless, precise reporting of LVDD in COVID-19 patients is currently lacking and assessment could be challenging. Methods: We performed an echocardiography study in COVID-19 patients admitted to ICU with the aim to describe the feasibility of full or simplified LVDD assessment and its incidence. We also evaluated the association of LVDD or of single echocardiographic parameters with hospital mortality. Results: Between 06.10.2020 and 18.02.2021, full diastolic assessment was feasible in 74% (n=26/35) of patients receiving full echocardiogram study. LVDD incidence was 46% (n=12/26), whilst the assessment produced different results (incidence 81%, n=21/26). Nine patients were hospital-survivors (39%); incidence of LVDD (full assessment) was not different between survivors (n=2/9, 22%) and non-survivors (n=10/17, 59%; p=0.11). Also, the E/e’ ratio lateral was lower in survivors (7.4 [3.6] vs non-survivors 10.5 [6.3], p=0.03). We also found that s’ wave was higher in survivors (average, p=0.01). Conclusion: In a small single-center study, assessment of LVDD according to latest guidelines was feasible in three quarter of COVID-19 patients. Non-survivors showed a trend towards greater LVDD incidence; moreover, they had significantly worse s’ values (all) and higher E/e’ ratio (lateral).

Background. The COVID-19 pandemic has spread across the world, leading to government measures associated with a negative impact on mental health. The aim of this study was to evaluate the impact of COVID-19 on depression, anxiety and resilience in Dutch people with cystic fibrosis (PwCF) or primary ciliary dyskinesia (PwPCD) and their caregivers during the pandemic. Methods. Adolescents (12-17 years), adults and caregivers of children (0-17 years) with CF or PCD completed questionnaires on depression (PHQ-9), anxiety (GAD-7) and resilience (BRS) between September 2020 and February 2021. The psychosocial impact of COVID-19 was measured by the Exposure and Family Impact Survey (CEFIS) Part 2. Mixed model analyses compared PHQ-9 and GAD-7 results to participants’ pre-pandemic scores. Results. 110 participants (10 PwCF, 31 PwPCD, 52 CF caregivers, 17 PCD caregivers) completed questionnaires during the pandemic. Pre-pandemic outcomes were available for 87 participants. The prevalence of symptoms of depression and anxiety (PHQ-9 or GAD-7 scores ≥5) in PwCF and PwPCD and their caregivers before and during the pandemic was high, with an increase in depression in PwCF (2.75; 95%-CI: 0.82 to 4.68) and increase in anxiety in CF caregivers (1.03; 0.09 to 1.96) during the pandemic. Resilience was within the normal range for all groups, CEFIS scores corresponded to a low to normal impact. Conclusion. PwCF and PwPCD and their caregivers were at high risk of increased depression and anxiety symptoms both before and during the pandemic, which emphasizes the importance of mental health screening and psychological care in CF and PCD.

We develop a mathematical model to study the effects of non-pharmaceutical interventions (NPIs) on the dynamics of an epidemic. The level of intervention is assessed as a fraction of the population being isolated and depends on the level of incidence of the epidemic in the population. We perform the mathematical analysis of the model and show that, depending on the choice of the prevalence-dependent isolation function, it is possible to create new endemic equilibria and to change the stability of the disease-free equilibrium for which the epidemic vanishes. The model is then applied to the case of the covid-19 pandemic. Several NPI management strategies are considered. In the case of a NPI intensity increasing with the level of infection, it is possible to avoid the initial epidemic peak of great amplitude that would have occurred without intervention and to stabilize the epidemic at a chosen and sufficiently low endemic level. In the case of a NPI intensity decreasing with the level of infection, the epidemic can be driven to extinction by generating an “Allee” effect: when the incidence is below a given level, the epidemic goes extinct while above it, the epidemic will still be able take hold at a lower endemic level. Simulations illustrate that appropriate NPIs could make the Covid-19 vanish relatively fast. We show that in the context of the covid-19 pandemic, most countries have not chosen to use the most efficient strategies.

Background: Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the US. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population-based hospitalization burden of 18 respiratory viruses (RV) over 4 years, from 7/1/2015 to 6/30/2019 among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania. Methods: We used population-based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden. Results: Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2,552; 30.1%), influenza A (2,299; 27.1%), RSV (1,082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non-SARS-CoV-2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and white (71%) patients with 60% of patients ≥65 years, 24% 50-64 years and 16% 18-49 years. The annual burden, ranged from 137-174/100,000 population for rhinovirus/enterovirus; 99-182/100,000 for influenza A; 56-81/100,000 for RSV. Among adults <65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age. Conclusions: These virus-specific ARI population-based hospital burden estimates showed significant non-influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy.

To understand dynamics of the COVID-19 disease realistically, a new SEIAPHR model has been proposed in this article where the infectious individuals have been categorized as symptomatic, asymptomatic and super-spreaders. The model has been investigated for existence of a unique solution. To measure the contagiousness of COVID-19, reproduction number R0 is also computed using next generation matrix method. It is shown that model is locally stable at disease free equilibrium point when R0 <1 and unstable for R0 >1. The model has been analyzed for global stability at both of the disease free and endemic equilibrium points. Sensitivity analysis is also included to examine the effect of parameters of the model on reproduction number R0. Couple of optimal control problems have been designed to study the effect of control strategies for disease control and eradication from the society. Numerical results show that the adopted control approaches are much effective in reducing new infections.

Spontaneous hemothorax occurs in the absence of trauma or iatrogenic causes. Etiologies of spontaneous hemothorax in children include connective tissue disease, neoplasia and coagulopathy which is associated with thromboembolic events. We present the case of a 10-year-old chronic hemodialysis patient with spontaneous hemothorax with a concurrent COVID 19 infection.

Kaposi's sarcoma is a common cancer associated with HIV infection. Since the COVID-19 pandemic, the prevalence of this pathology has increased. We report a case of a 33-year-old patient who presented with Kaposi's sarcoma associated with Covid-19 and HIV coinfection. It promotes the progression of cancers and increases mortality.

Although the COVID-19 lockdowns in 2020 had some environmental benefits, the pandemic’s impact on the global economy has also had conservation repercussions, especially in biodiverse nations. Ecuador, which is heavily reliant on petroleum, agricultural exports, and ecotourism, experienced a rise in poverty in response to pandemic shutdowns. In this study, we sought to quantify levels of illegal timber extraction and poaching before and after the start of COVID-19 lockdowns throughout two protected areas (Reserva Jama Coaque [JCR] and Reserva Bosque Seco Lalo Loor [BSLL]) in the endangered Pacific Forest of Ecuador. We analyzed chainsaw and gunshot acoustic data recorded from devices installed in the forest canopy from December 2019 to March 2020 and October 2020 to March 2021. Results from generalized linear mixed effects models indicated less chainsaw activity before lockdowns (post.lockdown = 0.571 + 0.196 SE, p-value = 0.004), although increased average rainfall also seemed to negatively affect chainsaw activity (avg.rainfall = -0.005 + 0.001 SE, p-value < 0.001). Gunshots were too infrequent to conduct statistical models; however, 87% of gunshots were detected during the ‘lockdown’ period. Observational data collected by rangers from these protected areas also noted an increase in poaching activities beginning mid to late 2020 and persisting into 2021. These results add to the steadily growing literature indicating an increase in environmental crime, particularly in biodiverse nations, catalyzed by COVID-19-related economic hardships. Identifying areas where environmental crime increased during pandemic lockdowns is vital to address both socioeconomic drivers and enforcement deficiencies to prevent further biodiversity loss and disease outbreaks and to promote ecosystem resilience. Our study also demonstrates the utility of passive acoustic monitoring to detect illegal resource extraction patterns, which can inform strategies such as game theory modeling for ranger patrol circuits and placement of real-time acoustic detection technologies to monitor and mitigate environmental crimes.

Late complications of COVID -19 infection are as important as the acute phase problems . A young woman with a history of COVID-19 infection and concomitant visual problems was admitted with exacerbation of dyspnea . During the admission, pulmonary embolism , myocarditis and fungal endocarditis were detected .

Recently spontaneous tension pneumomediastinum (PTM), pneumothorax (PT), and subcutaneous emphysema (SE) were reported as infrequent complications in COVID-19 patients. Early diagnosis and treatment could save the patients since these complications are related to poor prognosis and prolonged hospitalization. Here we report these complications in an Iranian patient.

The COVID-19 pandemic has disrupted seeking and delivery of healthcare. Different Australian jurisdictions implemented different COVID-19 restrictions. We used Australian national pharmacy dispensing data to conduct interrupted time series analyses to examine the incidence and prevalence of opioid dispensing in different jurisdictions. Following nationwide COVID-19 restrictions, the opioid incidence dropped by -0.40 [-0.50, -0.31], -0.33 [-0.46, -0.21] and -0.21 [-0.37, -0.04] /1000 people/week and prevalence dropped by -0.85 [-1.39, -0.31], -0.54 [-1.01, -0.07] and -0.62 [-0.99, -0.25] /1000 people/week in Victoria, New South Wales and other jurisdictions, respectively. Incidence and prevalence increased by 0.29 [0.13, 0.44] and 0.72 [0.11, 1.33] /1000 people/week, respectively in Victoria post-lockdown; no significant changes were observed in other jurisdictions. No significant changes were observed in the initiation of long-term opioid use in any jurisdictions. More stringent restrictions coincided with more pronounced reductions in overall opioid initiation, but initiation of long-term opioid use did not change.

RP7214 is a potent and selective inhibitor of human mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). This paper describes the results from a Phase 1 study that evaluated safety and pharmacokinetics of single and multiple ascending doses (SAD and MAD) and the food effect of RP7214 in healthy subjects. Target engagement of DHODH was also evaluated. A randomized, double-blind, placebo-controlled trial of single-dose (100, 200, and 400 mg QD) and multiple doses (200 and 400 mg BID for 7 days) followed by food effect at a single dose of 200 mg was conducted. A total of 18 healthy volunteers (HVs) (6 subjects in each of three cohorts) in the SAD part, 12 (6 subjects each in two cohorts) in the MAD part, and 12 in the food effect study were enrolled. RP7214 was well tolerated at all dose levels. None of the subjects reported any RP7214-related adverse events. RP7214 showed dose-proportional pharmacokinetics after single and multiple dosing. Steady-state concentrations were reached within about 3–6 days. The mean plasma half-life of RP724 at steady-state was approximately 13h. RP7214 showed accumulation on multiple dosing.. Food did not impact the absorption of RP7214. RP7214 showed dose-dependent inhibition of DHODH as measured by analyzing accumulating DHO levels, confirming target engagement. The rapid absorption and high systemic exposure of RP724 with a favorable safety profile shows the potential for the development of RP7214 in SARS-CoV-2 infection and acute myeloid leukemia. (NCT04680429). Keywords: RP7214, dihydroorotate dehydrogenase, SAD, MAD, HV

The two cases we present are the first to demonstrate novel manifestations of COVID-19- related interaction between the liver and the immune system in pediatric patients. Written informed consent was obtained from the parent/guardian to publish this report in accordance with the journal’s patient consent policy.

Introduction: Case definitions are used to guide clinical practice, surveillance, and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the CDC, ECDC, WHO, and UKHSA case definitions by age, region, and time. Case fatality ratios (CFR) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test-result were excluded. Results: 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC), and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients that met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.

We present the case of a previously healthy 36-year-old male with right eye discomfort, associated diplopia and dizziness as the primary clinical picture, seven days after a booster vaccination with the ChAdOx1-S (Oxford/AstraZeneca) COVID-19 vaccine.

Background: Hemostatic disturbances with coronavirus disease 2019 (COVID-19) can predispose to tricuspid and right heart thrombi in very rare instances. Aim: We describe a 29-year-old female patient without previous cause of thrombosis who developed large tricuspid valve thrombus (TVT) and moderate-to-severe tricuspid regurgitation (TR) during the course of COVID-19 infection. Materials and methods: Persistant fever and tachycardia with thrombocytopenia and high D-dimer increased the index of suspicion. The diagnosis was made by bedside transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR). Surgery was performed for thrombectomy and tricuspid valve replacement with a tissue valve. Discussion and conclusion: Detection of TVT in COVID-19 patients on the basis of high index of suspicion, bedside TTE and non-invasive CMR helps early surgical treatment and subsequent reduction of mortality and hospital stay.

Viral infection in cell culture and tissue is modeled with delay reaction-diffusion equations. It is shown that progression of viral infection can be characterized by the viral replication number, time-dependent viral load and the speed of infection spreading. These three characteristics are determined through the original model parameters including the rates of cell infection and of virus production in the infected cells. The clinical manifestations of viral infection, depending on tissue damage, correlate with the speed of infection spreading, while the infectivity of a respiratory infection depends on the viral load in the upper respiratory tract. Parameter determination from the experiments on Delta and Omicron variants allows the estimation of the infection spreading speed and viral load. Different variants of the SARS-CoV-2 infection are compared confirming that Omicron is more infectious and has less severe symptoms than Delta variant. Within the same variant, spreading speed (symptoms) correlates with viral load allowing prognosis of disease progression.

Remdesivir can precipitate fatal acute necrotizing pancreatitis especially in patients who previously suffer from hypertriglyceridemia.

Rationale: As a result of the SARS-CoV-2 pandemic, all pediatric pulmonary fellowship programs conducted virtual interviews for the first time in the Fall of 2020. This study aimed to understand the accuracy of virtual-interview derived-impressions of fellowship programs, as well as applicant preference for future fellowship interview cycles. Methods: A group of pediatric pulmonary fellows and Program Directors designed a REDCap survey. The survey was distributed to all first-year pediatric pulmonary fellows who participated in the 2020-2021 virtual interview season. Results: 23/52 (44%) of first-year pediatric pulmonary fellows completed the survey. 96% were able to form general impressions about fellowship programs during their virtual interviews. 96% reported that generally their fellowship experience matched their virtual-interview derived-impressions. 17 of 19 factors applicants use to rank programs had no statistically significant change (p > 0.05) in impression from virtual interview to fellowship experience. The two factors with a statistically significant (p < 0.05) change in impression were patient care related – volume of ‘bread and butter’ pediatric pulmonary patients and volume of tertiary care pediatric pulmonary patients. 87% prefer some form of in-person interview option in future application cycles. A tiered interview format in which applicants are first invited to a virtual interview day followed by an optional in-person second look day was the most popular preference for future interview cycles (48%). Conclusions: Virtual interviews may provide accurate representations of pediatric pulmonary fellowship programs and applicants prefer some type of in-person interview option in future application cycles.

Ventricular septal rupture (VSR) is a rare complication of myocardial infarction that requires surgical repair. Herein we describe a case of intraoperative VSR requiring a second bypass run and patch repair. This case highlights the importance of early reperfusion and poses concern for delayed patient presentation during the COVID-19 pandemic.

Guillain- Barre Syndrome (GBS), an autoimmune neurological disease of peripheral nerves has been causally associated with COVID-19 vaccination in adults. However, no such report has been published so far in children. We describe a 13-year old female child who presented to emergency department with complaints of bilateral upper limb, lower limb and truncal weakness over three days following first dose of recombinant protein subunit COVID-19 vaccine (Corbevax). Clinical examination and nerve conduction studies showed pure motor axonal polyneuropathy with absent compound muscle action potential (CMAP) in all sampled nerves of upper and lower limbs which was consistent with the diagnosis of GBS after ruling out possible alternative aetiologies. A temporal association between first dose of protein subunit COVID-19 vaccine administered a day prior and symptom onset was noted. The causality assessment using World Health Organization (WHO) tool for adverse event following immunization (AEFI) assessment indicated vaccine-product related reaction categorized as A1. Patient’s clinical condition improved after seven sessions of plasmapheresis. The purpose of this report is to create awareness among the health care professionals about COVID-19 vaccine induced GBS in children as early diagnosis and management can be critical in avoiding complications and improving patient outcomes.

Aircraft cabins have high-performance ventilation systems, yet typically hold large numbers of people in close proximity for long periods. The current study estimated airborne virus exposure and infection reductions for vacant middle seats and masking in aircraft. Tracer particle data reported by U.S. Transportation Command (TRANSCOM) and CFD simulations reported by Boeing were used, along with NIOSH data, to build nonlinear regression models with particle exposure and distance from particle source as variables. These models that estimate exposure at given distances from the viral source were applied to evaluate exposure reductions when middle seats are vacant compared to full occupancy. Reductions averaged 54% for the seat row where an infectious passenger is located and 36% for a 24-row cabin containing one infectious passenger, with middle seats vacant. Analysis of the TRANSCOM data showed that universal masking (surgical masks) reduced exposures by 62% and showed masking and physical distancing provide further reductions when practiced together. For a notional scenario involving 10 infectious passengers, compared with no intervention, masking, distancing, and both would prevent 6.2, 3.8 and 7.6 secondary infections, respectively, using the Wells-Riley equation. These results suggest distancing and masking reduce SARS CoV-2 exposure risk when an infectious passenger is present.