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.

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.

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.

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.

Several hundred cases of placental hemangiomas have been reported in the literature. However, the umbilical cord is extremely uncommon as a site of occurence.We report the first case of hemangioma of the umbilical cord synchronous to maternal infection with covid-19.We aim to study the clinicopathological characteristics of this singular entity.

Abstract Background. Still now, COVID-19 is a public health concern in both developed and developing countries. Risk perception has been studied in different countries with different population groups. However, there have been few studies conducted risk perception on elderly people and there is no study on elderly people’ in Ethiopia including this study area.This study aimed to assess coronavirus disease low risk perception level and associated factors among the elderly. Methods. To carry out this study among elders in Areka town from 01 August 2021 to 30 August 2021, a community-based cross-sectional study was used. Multi-stage sampling method was applied to select study participants. The data were collected through a structured questionnaire with the mobile application of Open Data Kit mobile(ODK). Results. This study showed that individuals with age range of 65 to 74 [AOR= 4.76, 95% CI (2.35-9.64)], poor practice on preventing coronavirus disease [AOR= 2.39, 95% CI (1.51-3.78), low trust level in medical professionals [AOR=2.44, 95%CI (1.45-4.10)], no history of coronavirus disease [AOR=6.45, 95%CI (2.02-20.58)], poor perceived self-efficacy for preventive practice [AOR=2.25, 95% CI (1.43-3.54)] were identified as associated factors of low risk perception. Conclusions. In the current study area, the perception of risk of coronavirus disease was affected by age, perceived self-efficacy, trust in medical professionals, preventive practice, and history of coronavirus disease. Including Ethiopia, the findings of this study would help for developing countries to generate evidence-based policy decisions for elderly people during COVI-D-19 pandemic and future pandemic(s). Keywords: Associated factors, Coronavirus, Elderly, Ethiopia, Perception

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.

This study reports a patient developing TEN after the first dose of (BBIBP-CorV). He developed numerous purpuric and dusky patches with flaccid bullae and areas of epidermal detachment covered more than 30% of the body area within 6 days. After treatment with dexamethasone and cyclosporin, he recovered within 14 days.

This study aimed to investigate epidemiological, clinical, and laboratory features of children with COVID-19 to identify predictors for pulmonary involvement. We conducted a retrospective, single-center study of pediatric COVID-19 at a tertiary care hospital in Turkey between December 2020 and June 2021. A total of 126 children (70 males, 55.6%) were examined during the study period. Their mean age was 74.73 ± 81.11 months (range, 1–216 months). The most frequent COVID-19 symptoms were fever (65.9%), cough (52.4%), and shortness of breath (18.3%). Ten patients required noninvasive mechanical ventilation. Sixty-nine patients (54.8%) had pneumonia. Longer duration of fever and the presence of cough were significantly associated with pulmonary involvement. In children with pneumonia, the C-reactive protein (CRP), procalcitonin levels, erythrocyte sedimentation rate (ESR), and viral load were significantly higher and lymphocyte and thrombocyte counts were significantly lower than in children without pneumonia. The cutoff viral load, CRP, and procalcitonin values for predicting pulmonary involvement were 26.5 cycle threshold (Ct; 95% confidence interval [CI], 0.54–0.74; sensitivity, 0.65; specificity, 0.56; area under curve [AUC]: 0.647, p = 0.005), 7.85 mg/L (95% CI, 0.56–0.75; sensitivity, 0.66; specificity, 0.64; AUC = 0.656; p = 0.003) and 0.105 ng/mL (95% CI, 0.52–0.72; sensitivity, 0.55; specificity, 0.58; AUC = 0.626; p = 0.02), respectively. High CRP, procalcitonin levels, ESR, and viral load and low lymphocyte and thrombocyte counts can predict pulmonary involvement in children with COVID-19, so better management may be provided for good prognosis.

To report a case of Vogt-Koyanagi-Harada disease (VKH) in a 27-year-old male two weeks proceeding COVID-19 infection onset. Severe complications of VKH can be avoided by early diagnosis and adequate treatment with corticosteroids and immunosuppressants. It is possible that COVID-19 was a potential immunological trigger of VKH in our patient.

Fluvoxamine for COVID-19 outpatients: for the time being, we might prefer to curb our optimismVladimir TrkuljaRunning head : Fluvoxamin and COVID-19 outpatientsKey words : fluvoxamine, COVID-19, outpatients, hospitalizationsVladimir Trkulja, MD, PhDDepartment of PharmacologyZagreb University School of MedicineŠalata 1110000 Zagreb, Croatiae-mail: vladimir.trkulja@mef.hrNumber of words: 613Number of figures/tables: 1To the Editor,A rather elaborate pharmacodynmics rationale 1 and sound pharmacokinetic reasoning 2 support the use of fluvoxamin in early phases of the COVID-19 disease. Two recent meta-analyses, 3, 4 both based on the same three randomized placebo-controlled trials, emphasized the benefit of early fluvoxamine treatment in non-vaccinated adult symptomatic mild COVID-19 outpatients in terms of a reduced risk of disease deterioration over subsequent days. In the first of the meta-analyzed trials, Stop COVID 15, primary outcome was hospitalization or incident hypoxemia needing oxygen treatment within 15 days. The trial was rather small, particularly for a binary outcome (fluvoxamine 2x100 to 3x100 mg/day over 15 days, n=80; placebo n=72) and recorded only 6 events (all with placebo) 5. Stop COVID 2 6followed the same design/outcome, and was stopped at an advanced stage for operational reasons but did not indicate any benefit [incidence 11/272 (4.0%) fluvoxamin vs. 12/275 (4.4%) placebo)]. The meta-analytical pooled estimates 3, 4 were dominated by the results of the TOGETHER trial 7 (fluvoxamine 2x100 mg/day, 10 days) that reported a marked relative reduction in the risk of the primary outcome (emergency room stay of at least 6 hours or hospitalization; over 28 days): 79/741 (11.0%) vs. 119/756 (16.0%), RR=0.69 (95% CrI 0.53-0.90) 7. By far the most events were hospitalizations, but no clear-cut benefit was obvious in this respect [75/741 (10.0%) vs. 97/756 (13.0%), OR=0.77 (0.55-1.05)7]. The meta-analysis by Lee et al.3 focused on hospitalizations and reported a 25% relative risk reduction by a frequentist method (RR=0.75, 95%CI 0.58-0.97), while the Bayesian analysis (weakly informative neutral prior) indicated somewhat more uncertainty (RR=0.78, 95%CrI 0.58-1.08; 81.6% probability of RR ≤0.90) 3. Guo et al.4 employed only frequentist pooling to indicate a marked benefit regarding “study-defined outcomes” (RR=0.69 95%CI 0.54-0.88) and somewhat more uncertainty regarding “hospitalizations” (RR=0.79, 95%CI 0.60-1.03) 4. In the meantime, a report was pubslihed of a randomized placebo-controlled trial conducted in 2020 in Korean outpatients (∼10 days of fluvoxamine 2x100 mg/day)8. It was stopped early for operational reasons8, and the primary outcome (as in Stop COVID trials) was observed in 2/26 treated and 2/26 placebo patients8. Figure 1 depicts meta-analysis of “study-defined primary outcomes” and of “hospitalizations” that uses the same frequentist and Bayesian methodology as used by Lee et al.3 except that (i) it includes the Korean data8 and (ii) employs Hartung-Knapp-Sidik-Jonkman correction shown to yield the least biased confidence interval coverage with small number of trials considerably varying in size9: (a) uncertainty about the benefit regarding “study-defined outcomes” (Figure 1A) is indicated by both the frequentist and Bayesian intervals extending to >1.0 and prediction intervals extending well >1.0. Probability of at least 10% relative risk reduction is 90.0%; (b) uncertainty about the benefit regarding “hospitalizations” (Figure 1B) is even more obvious, with estimate intervals exceding >1.10 (and further extended predictions intervals), with only 73.8% probability of at least 10% relative risk reduction. If one were to disregard two small trials with a few events (and, hence, fragile estimates that could have been by chance, at least in part) 5, 8, for the time being one would be looking at Stop COVID 2 and TOGETHER trial. This means 86/1013 hospitalization events with fluvoxamine vs. 109/1031 events with placebo, and a considerable uncertainty about any practically relevant effect: (i) frequentist RR=0.803 (95%CI 0.422-1.530); (ii) Bayesian RR=0.840 (95%CrI 0.613-1.170) and only 67.4% probablity of at least 10% relative risk reduction. Hopefully, the on-going trials (depicted in ref. 3) will resolve this uncertainty, but presently we might prefer to be cautios rather than overtly optimistic about the actual extent of benefit conveyed by early fluvoxamine treatment in COVID-19 outpatients.

This is a 3-week-old female, her presenting complaints were low-grade fever and a blocked nose for one day. Eventually, she developed progressive desaturation, hypotension, and poor perfusion due to severe pulmonary hemorrhage. Then, she developed cardiac arrest and was declared dead.

In the present paper we investigate the qualitative behaviour of a fractional SEIR model with general incidence rate function and time delay where the fractional derivative is defined in the Caputo sense. The basic reproduction number $\mathcal{R}_{0}$ is derived using the method of next generation matrix and we give a complete study of local stability of both free and endemic equilibrium. Using Liapunov method we prove the global stability of free and endemic equilibrium under some hypotheses on the parameters of the system. Finally to illustrate our results, we use the model to predict the first peak of the COVID-19 epidemic in Algeria.

Background: Multisystem Inflammatory Syndrome in Children (MISC) is a phenomenon that appeared in children infected with or exposed to SARS-CoV-2. The typical onset of MISC is 4-6 weeks following SARS-CoV-2 infection and is formulated to be due to an immune response. Methods: Our study retrospectively analyzed data from a tertiary center in UAE of MISC patients who were admitted to either general pediatric wards or pediatric intensive care (PICU) or who came exclusively for follow-up (post PICU admission) from May 2020 to August 2021.   Results: The total sample size is 50 patients and the study included a comparison of PICU admissions with none PICU admissions. The PICU sample size was 18 patients, 50% females, with mean age of 8.3 years all were previously healthy. PICU patients had deranged blood counts with a lower hemoglobin count, a more pronounced lymphopenia and thrombocytopenia along with hypoalbuminemia. PICU patients presented with relatively higher inflammatory markers: CRP, PCT, ferritin and D-dimer. Immunological studies were significantly higher for IL-6 levels in PICU patients. On echocardiography, higher myocardial dysfunction was more notable in patients admitted to PICU. Children admitted in PICU were provided with more extensive therapy. As part of our study course, we re-evaluated our PICU patients twice, once at 48 hours post PICU admission and again 4-6 weeks after discharge from the hospital. No deaths have been recorded in the cohort. Conclusion: This study evaluated risk factors of MISC and potential severity features. Follow up of patients on discharge showed improvement across all domains.