Gastrointestinal features of the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection in selected referral hospitals in Iran

Background and purpose: Multisystem Inflammatory Syndrome in Children (MIS-C) occurs after having COVID-19. The severity and outcomes of COVID-19 with gastrointestinal symptoms are higher. The aim of this study was to investigate gastrointestinal manifestations in MIS-C patients in selected referral hospitals in Iran to obtain comprehensive information about the treatment and prevention of MIS-C. Materials and methods: In this cross-sectional study, all MIS-C patients <21 years in Dec 2019 to Oct 2021 were included. The patients were identified by the Centers for Disease Control and Prevention (CDC) checklist and data were analyzed applying t-test and Chi-square in STATA11. Results: There were 225 patients with a median age of 55 months (26-96 months), including 59.56% boys and all had fever on admission. At least one gastrointestinal symptom was seen in 200 patients and the most common symptoms were vomiting (60.9%) and abdominal pain (45.77%). Almost 60% of the patients had positive RT-PCR results. Among the patients with and without gastrointestinal symptoms 85.5% and 48% were admitted to intensive care unit (ICU), respectively. There were significant differences between the two groups in respiratory symptoms, ALT, AST, NT-pro BNP, ESR, and PLT (P < 0.05). All patients without gastrointestinal symptoms were discharged but nine patients in the group with gastrointestinal symptoms deceased. Conclusion: According to the current study, gastrointestinal symptoms are common in MIS-C patients and are associated with higher rates of death and intensive care unit admission. Therefore, in providing services to COVID-19 patients, all typical and atypical signs and symptoms should be considered to prevent unnecessary interventions.

SIRS epidemic modeling using fractional-ordered differential equations: Role of fear effect

In this paper, an SIRS epidemic model using Grunwald–Letnikov fractional-order derivative is formulated with the help of a nonlinear system of fractional differential equations to analyze the effects of fear in the population during the outbreak of deadly infectious diseases. The criteria for the spread or extinction of the disease are derived and discussed on the basis of the basic reproduction number. The condition for the existence of Hopf bifurcation is discussed considering fractional order as a bifurcation parameter. Additionally, using the Grunwald–Letnikov approximation, the simulation is carried out to confirm the validity of analytic results graphically. Using the real data of COVID-19 in India recorded during the second wave from 15 May 2021 to 15 December 2021, we estimate the model parameters and find that the fractional-order model gives the closer forecast of the disease than the classical one. Both the analytical results and numerical simulations presented in this study suggest different policies for controlling or eradicating many infectious diseases. [ FROM AUTHOR] Copyright of International Journal of Biomathematics is the property of World Scientific Publishing Company 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 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 . (Copyright applies to all s.)

Evaluation of Urine L-FABP Point of Care Kit in the Philippines as Predictive Marker of Clinical Severity of COVID-19 (EPOCH COVID study)

Background: The search for simple clinical and laboratory markers to help predict the clinical severity of patients presenting with COVID-19 has prompted this study to look at the predictive value of urine L-FABP (Liver Type-Fatty Acid Binding Protein) point-of-care test kit at the initial presentation of COVID-19 patients to the hospital. Method(s): The validation study prospectively included 109 consecutive patients with mild to moderate COVID-19, mean age of 52.2 years (range 19-84) presenting at the Emergency Rooms of 4 participating Metro-Manila hospitals from February to April 2021, with available data for analysis for 103 patients. Urine L-FABP POC (Point-of-Care) test and other clinical parameters and the level of severity of COVID-19 were determined at Day 0, Day 4 and Day 7. Computations for Sensitivity, Specificity, Positive and Negative Predictive values and Likelihood ratios were performed Results: Twenty-three patients tested positive for urine L-FABP, out of the 103 patients analyzed, while 80 tested negative. Of the 23 patients who tested positive for urine L-FABP, 6 has progressed in severity, while 17 did not progressed. Of the 80 patients who tested negative for urine L-FABP, 13 progressed, while 67 did not progressed in severity. Giving a Sensitivity of 31.58%, Specificity of 79.76%, Positive predictive value of 26.09%, Negative predictive value of 83.75%. Combining urine L-FABP and initial clinical parameters like SIRS (Systemic Inflammatory Response Syndrome) criteria to predict progression of severity yielded a higher Specificity of 91.67 % and Negative Predictive value of 84.62%. Conclusion(s): The study shows the utility of initial urine L-FABP POC test as a negative screening test in triaging adult patients presenting to the ER with mild to moderate COVID-19. Patients at the ER with a negative urine L-FABP test, will most likely not progressed to severe COVID-19. Combining clinical parameters like SIRS Criteria with the urine L-FABP result can increase the negative predictive value.Copyright © The PHILIPPINE JOURNAL OF INTERNAL MEDICINE is a peer reviewed journal and a copyrighted publication of the Philippine College of Physicians.

Systemic Inflammatory Response Syndrome After Extracorporeal Membrane Oxygenation Decannulation in COVID-19 Patients.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is frequently observed following decannulation from extracorporeal membrane oxygenation (ECMO). Differentiating cytokine release due to infection from endothelial injury from cannula removal and/or discontinuation from the ECMO circuit has been shown to impact treatment and outcomes. This response, however, may be complicated in COVID-19 patients due to prevalent glucocorticoid and immune modulator use. It remains unclear whether COVID-19 infection and/or associated immune modulator use impact the incidence of SIRS following decannulation. OBJECTIVES: The aim of this study is to investigate the incidence of the SIRS phenomenon and associated outcomes in patients with COVID-19 after ECMO decannulation. METHODS: An IRB-approved retrospective chart review of all patients who survived ECMO between June 31, 2010 and July 7, 2021 was done to identify patients who experienced SIRS within 48 hours of decannulation from ECMO support. Patients with COVID-19 were confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV2. SIRS was confirmed when two out of three of the following criteria were met: fever, leukocytosis, and/or initiation/escalation of vasopressors. Patients who developed post-ECMO SIRS were then distinguished based on the presence of infection. Infection was defined by the presence of either a new or positive culture following decannulation. We compared the incidence of SIRS and infection within 48 hours of decannulation in patients with and without COVID-19. RESULTS: We identified 227 eligible patients who survived ECMO. Twenty-eight patients (12%) had COVID-19. Of these patients, ten patients with COVID-19 (36%) experienced post-ECMO SIRS, including those with true SIRS (n=3) and associated infections (n=7). Five of the ten patients with COVID-19 who experienced post-ECMO SIRS were exposed to immune modulators within two weeks of decannulation. Ninety-five (42%) patients without COVID-19 developed post-ECMO SIRS. Thirty-day survival in COVID patients who experienced post-ECMO SIRS compared to COVID patients who did not experience post-ECMO SIRS was 73% vs. 94%. (p=0.11). CONCLUSION: Post-ECMO SIRS is common. The incidence of SIRS following decannulation was similar when historically compared to non-COVID patients who survived ECMO in a previously reported cohort from our institution. Immune-modulation exposure within two weeks of decannulation did not affect the incidence of SIRS in patients with COVID-19.

COVID-19 infection-associated multisystem inflammatory syndrome and cytokine storms in children

Multisystem inflammatory syndrome in children(MIS-C) is a systemic inflammatory syndrome with multiorgan dysfunctions. Most of the children have evidence of severe acute respiratory syndrome-associated coronavirus(SARSCoV-2) infection or a history of exposure to patients with coronavirus disease 2019(COVID-19). Children often present with fever, gastrointestinal symptoms, cardiac dysfunctions, shock and other multi-system symptoms. Cytokine storm(CS) is an inflammatory response triggered by external stimulations. Factors causing CS include iatrogenic,pathogenic, monogenic or autoimmune diseases. The pathogenesis of MIS-C is still unclear, which may be related to the over-response of immune system caused by SARS-CoV-2 infections.In this paper, the clinical characteristics of COVID-19 infection-related MIS-C are summarized, and the relationship between MIS-C and CS is discussed, aiming to provide references for the mechanistic investigation and clinical diagnosis of MIS-C.

A Sir Model for Viral Growth of Coronavirus: A System Dynamics Approach

In this paper, a system dynamics model depicts the viral growth of COVID-19 at an exponential rate. The outbreak of Corona virus was started from the Feb 26, 2020 when the first case was reported in Pakistan. Local bodies and law enforcing agencies had taken initial preventive measures to restrict the COVID-19 to a particular locality but all in vain. The infected people were increasing every day rising the stocks of recoveries and deaths. Numbers of infected people were alarming and a need was felt to develop the model to calculate the existing reproduction number and transmission rate and highlight its varied values in coming days. People-oriented measures and government-based policies must be explored to fight against this deadly disease. This paper aims the development of epidemic model using the system dynamic framework on simulation software STELLA. The objective of the research is to experiment with the model to replicate the progression of the communicable disease and probe the multiple combinations of the people-based and government-based measures to reduce its spread. The containment measures are of two types;people-based measures and government-based measures and both directly affect the reproduction number and infection growth fraction for mitigating the spread of deadly coronavirus. Combined efforts of public and government can combat this pandemic. Reduced degree of reproduction number and infection growth fraction are the key metrics to judge and evaluate the effectiveness of containment measures. This research points to more holistic combination of public and government-oriented measures that play the vital role to flatten the curve and reduce its spread affecting the reproduction number. Simulation results have been traced to replicate the real-life settings against four combinations of containment measures in tabular form and graphical form. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Autophagy in Inflammatory Response against SARS-CoV-2.

The coronavirus disease pandemic, which profoundly reshaped the world in 2019 (COVID-19), and is currently ongoing, has affected over 200 countries, caused over 500 million cumulative cases, and claimed the lives of over 6.4 million people worldwide as of August 2022. The causative agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Depicting this virus' life cycle and pathogenic mechanisms, as well as the cellular host factors and pathways involved during infection, has great relevance for the development of therapeutic strategies. Autophagy is a catabolic process that sequesters damaged cell organelles, proteins, and external invading microbes, and delivers them to the lysosomes for degradation. Autophagy would be involved in the entry, endo, and release, as well as the transcription and translation, of the viral particles in the host cell. Secretory autophagy would also be involved in developing the thrombotic immune-inflammatory syndrome seen in a significant number of COVID-19 patients that can lead to severe illness and even death. This review aims to review the main aspects that characterize the complex and not yet fully elucidated relationship between SARS-CoV-2 infection and autophagy. It briefly describes the key concepts regarding autophagy and mentions its pro- and antiviral roles, while also noting the reciprocal effect of viral infection in autophagic pathways and their clinical aspects.

Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature.

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.

Investigation of acute-phase protein concentrations in healthy and various diseased cats.

This study aimed to evaluate the concentrations of α1-acid glycoprotein (AGP), haptoglobin (Hp), serum amyloid-A (SAA) and ceruloplasmin (Cp) in healthy and various diseased cats and establish reference intervals (RIs) for these acute phase proteins (APPs) in healthy cats. The animal material of the study consisted of 40 healthy cats and 152 cats with various diseases. The serum APPs in the diseased group were higher than those in the healthy group, and age affected Cp concentration in healthy cats. Also, the systemic inflammatory response syndrome (SIRS) positive (+) group had significantly higher AGP concentrations than the SIRS negative (-) group. In conclusion, this study contributes to the limited number of studies on RIs in serum APPs concentrations in healthy cats. The results of this study suggest that APPs are valuable diagnostic tools for identifying the inflammatory processes of various diseases, and AGP concentration could help determine the severity of the inflammatory condition.

Clinical Profile of Patients Presenting With Sepsis to the Emergency Department of a Tertiary Care Hospital in Wardha During the COVID Pandemic (June 2020-June 2021).

Background Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Septic shock, multi-organ dysfunction, and death occur in severe cases with reduced blood flow to vital organs. Sepsis contributes to 15-20% of all global deaths. Through this study, we intend to evaluate the clinical profile and study the common blood investigatory panels along with organisms causing sepsis in patients presenting with sepsis in the emergency department during the COVID pandemic. In addition, the study was also done to estimate the prevalence of sepsis and compare patients having sepsis with serum lactate, sepsis with Systemic Inflammatory Response Syndrome (SIRS) criteria, and sepsis with quick Sepsis Related Organ Failure Assessment (qSOFA) score. Method Observational retrospective study to evaluate patients presenting with sepsis diagnosed by the Third International Consensus Definitions for Sepsis and Septic Shock" criteria presenting to the emergency department of Acharya Vinoba Bhave Rural Hospital (AVBRH) affiliated to Jawaharlal Nehru Medical College (JNMC), Wardha during COVID pandemic (June 2020-June 2021). Results The majority of the patients presented with fever (42%), and very few presented with altered mental status (8%). Seventy-four percent of the study population did not show any bacterial growth on blood culture, but out of the remaining 26%, blood culture, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pnemoniae were the significant microbes. Amongst qSOFA, SIRS criteria, and serum lactate as a screening tool for sepsis, SIRS is the most sensitive for screening sepsis patients. Conclusion Staphylococcus aureus, Pseudomonas aerugenosa, and Klebsiella pneumoniae were the major contributors in the development of sepsis in COVID-19-associated infection. The presence of raised leukocyte counts and serum lactate should alarm clinicians of possible sources of infection. The timely initiation, rapid de-escalation of empirical antibiotics, and strict compliance with infection control practices should be accomplished to reduce the occurrence of multidrug resistance organisms.

Dynamical behavior of SIRS model incorporating government action and public response in presence of deterministic and fluctuating environments

In the present article, global characteristics of a generalized SIRS (susceptible-infected-recovered-susceptible) epidemic model have been investigated incorporating government policy, public response and social behavioral reaction. The effects of environmental fluctuations and time-dependent control strategies on the disease dynamics have also been analyzed. In the case of deterministic model, it is shown that the disease invades in this system when the basic reproduction number (R-0) is greater than 1, whereas the dynamics of the stochastic model can be controlled by its associated basic reproduction number R-s. Specifically, this work emphasizes the importance of nonlinear dynamic analysis of epidemic modeling, as well as the significant impact of social and government actions on disease dynamics. Numerical figure depicts that the governmental action plays a crucial role to control an epidemic situation, and the system turns out to be disease-free sooner if the government takes action at an early stage during a disease outbreak. Furthermore, one of the most key developments is that random fluctuations can prevent disease outbreaks, which can lead to the development of useful control techniques to restrict disease dynamics. The governmental actions and the clinical treatment are considered to be the effective control pair in this model, and it can be observed that the simultaneous implementation of the control strategies significantly reduces the disease burden.

Coupling compartmental models with Markov chains and measure evolution equations to capture virus mutability

The COVID-19 pandemic lit a fire under researchers who have subsequently raced to build models which capture various physical aspects of both the biology of the virus and its mobility throughout the human population. These models could include characteristics such as different genders, ages, frequency of interactions, mutation of virus, etc. Here, we propose two mathematical formulations to include virus mutation dynamics. The first uses a compartmental epidemiological model coupled with a discrete-time finite-state Markov chain. If one includes a nonlinear dependence of the transition matrix on current infected, the model is able to reproduce pandemic waves due to different variants. The second approach expands such an idea to a continuous state-space leveraging a combination of ordinary differential equations with an evolution equation for measure. This approach allows to include reinfections with partial immunity with respect to variants genetically similar to that of first infection. [ FROM AUTHOR] Copyright of Mathematical Models & Methods in Applied Sciences is the property of World Scientific Publishing Company 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 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 . (Copyright applies to all s.)

An SIRS model with nonmonotone incidence and saturated treatment in a changing environment.

Nonmonotone incidence and saturated treatment are incorporated into an SIRS model under constant and changing environments. The nonmonotone incidence rate describes the psychological or inhibitory effect: when the number of the infected individuals exceeds a certain level, the infection function decreases. The saturated treatment function describes the effect of infected individuals being delayed for treatment due to the limitation of medical resources. In a constant environment, the model undergoes a sequence of bifurcations including backward bifurcation, degenerate Bogdanov-Takens bifurcation of codimension 3, degenerate Hopf bifurcation as the parameters vary, and the model exhibits rich dynamics such as bistability, tristability, multiple periodic orbits, and homoclinic orbits. Moreover, we provide some sufficient conditions to guarantee the global asymptotical stability of the disease-free equilibrium or the unique positive equilibrium. Our results indicate that there exist three critical values [Formula: see text] and [Formula: see text] for the treatment rate r: (i) when [Formula: see text], the disease will disappear; (ii) when [Formula: see text], the disease will persist. In a changing environment, the infective population starts along the stable disease-free state (or an endemic state) and surprisingly continues tracking the unstable disease-free state (or a limit cycle) when the system crosses a bifurcation point, and eventually tends to the stable endemic state (or the stable disease-free state). This transient tracking of the unstable disease-free state when [Formula: see text] predicts regime shifts that cause the delayed disease outbreak in a changing environment. Furthermore, the disease can disappear in advance (or belatedly) if the rate of environmental change is negative and large (or small). The transient dynamics of an infectious disease heavily depend on the initial infection number and rate or the speed of environmental change.

Orchitis as an unusual manifestation in multisystem inflammatory syndrome in children

This is a case report about an 8-year old boy who presented with complaints of fever for 5 days, loose stools, abdominal pain, and erythema of the palms and soles for 3 days. There was a history of short duration fever in all his family members 1 month back, but none of them were tested for COVID-19. On admission, the patient was febrile and had erythematous extremities. There was no organomegaly. He presented with hypotensive shock which was managed with fluid boluses and inotrope support. Fever workup including cultures were negative. His COVID-19 antibody was positive (16.17 index units). Inflammatory markers were elevated: ESR=50 mm/h=;C reactive protein=51 mg/dL;ferritin=>1000 ng/mL;D dimer=8260 ng/mL. Echocardiogram was normal and he was managed with intravenous immunoglobulin due to meeting the criteria for multisystem inflammatory syndrome (MISC) in children. The patient's fever subsided within 48 hours and his inflammatory markers showed declining trend. On the third day of becoming afebrile, the child complained of swelling, pain, and redness of right scrotum. There was no recurrence of fever, nor parotid swelling associated with orchitis. On examination, the right testis was enlarged, tender, located in the normal anatomic position with an intact ipsilateral cremasteric reflex. testicular tension was ruled out by ultrasound doppler. The unilateral orchitis was managed with supportive measures and subsided by 48 hours.

An Optimal Control of SIRS Model with Limited Medical Resources and Reinfection Problems

COVID-19 is a global public health problem that causes severe acute respiratory syndrome (SARS). It is also extremely contagious with rapidly increasing death rates. In this paper, we propose an optimal control model with SIRS (Susceptible-Infected-Recovered-Susceptible) kinetics to examine the effects of several intervention measures (e.g., vaccination and treatment) under the limited medical resources scenarios. This model is also employed to investigate the possibility of reinfection because of the fading of immunity problem. As a case study, the modeling framework is parametrised using COVID-19 daily confirmed and recovered cases in Malaysia. The parameters have been approximated by relying on the model's best fit to actual data published by the Malaysian Ministry of Health (MOH). Our numerical simulation results show that the inclusion of optimal control components with vaccination and treatment strategies would dramatically reduce the number of active cases even in the presence of reinfection forces. Regardless of the relative weightage (or costs) of vaccination and treatment, as well as the possibility of reinfection, it is critical to plan effective COVID-19 control measures by vaccinating as many people as possible (and as early as possible). Overall, these insights help explore the importance of intervention measures and the allocation of medical resources to control the severity of this pandemic.

Immunopatogenetic basis of the severity of COVID-19. Literature review

Relevance. The outbreak of COVID-19 began in late 2019 in Hubei Province, China. Already in the first quarter of 2020, the disease spread around the world. On March 11, 2020, the WHO declared a COVID-19 pandemic. The first cases of the disease in Kazakhstan were registered in March 2020. The aim of the study: a systematic search for scientific information about the socially significant disease COVID-19 and its immunopathogenetic basis for the severity of the course. Search strategy: Research publications were searched in PubMed, ResearchGate, GoogleScholar databases. A total of 325 references were found, of which 89 were selected for analysis.

Special Section: COVID-19. (Special Section: COVID-19.)

This special issue includes more than 20 articles on various COVID-19 topics of interest to the busy pediatric practitioner. Clinical features include brief reports of rare and unusual presentations or sequelae of COVID-19 infection or COVID-19 vaccination. Several studies report on multisystem inflammatory syndrome of children clinical manifestations. The reader will also find various epidemiologic reports from well-known pediatric centers, both domestic and international, on COVID-19's impact on hospitalization, neonatal care, emergency room visits, outpatient care, children with special needs, and children in special populations. The mental health crisis that COVID-19 has caused among children and adolescents as well as COVID-19 vaccination attitudes and hesitancy are also addressed.

Special Issue: COVID-19 and immunity. (Special Issue: COVID-19 and immunity.)

This special issue contains five review articles based on the talks at the Japanese Society for Immunology held online-only on 8 December 2020 and focused on the topic 'COVID-19 and Immunity'. Topics covered include: immune responses against SARS-CoV-2;the role of IL-6 in the cytokine storm;the development of COVID-19 vaccines;the immunogenicity and safety of COVID-19 vaccines;and changes to chromatin structure during virus infections.

Asymptotic behavior of the solutions for a stochastic SIRS model with information intervention.

In this paper, a stochastic SIRS epidemic model with information intervention is considered. By constructing an appropriate Lyapunov function, the asymptotic behavior of the solutions for the proposed model around the equilibria of the deterministic model is investigated. We show the average in time of the second moment of the solutions of the stochastic system is bounded for a relatively small noise. Furthermore, we find that information interaction response rate plays an active role in disease control, and as the intensity of the response increases, the number of infected population decreases, which is beneficial for disease control.

Performance of NEWS, qSOFA, and SIRS Scores for Assessing Mortality, Early Bacterial Infection, and Admission to ICU in COVID-19 Patients in the Emergency Department.

SARS-CoV-2 infection has a wide spectrum of presentations, from asymptomatic to pneumonia and sepsis. Risk scores have been used as triggers for protocols that combine several interventions for early management of sepsis. This study tested the accuracy of the score SIRS, qSOFA, and NEWS in predicting outcomes, including mortality and bacterial infection, in patients admitted to the emergency department (ED) during the COVID-19 pandemic. We described 2,473 cases of COVID-19 admitted to the ED of the largest referral hospital for severe COVID-19 in Brazil during the pandemic. SIRS, qSOFA and NEWS scores showed a poor performance as prognostic scores. However, NEWS score had a high sensitivity to predict in-hospital death (0.851), early bacterial infection (0.851), and ICU admission (0.868), suggesting that it may be a good screening tool for severe cases of COVID-19, despite its low specificity.