Systemic Inflammatory Syndrome Research Articles

Kawasaki disease before and during the COVID-19 pandemic: a single-center comparative study in Switzerland.

Kawasaki disease is a rare systemic inflammatory syndrome that mainly affects children under five years of age and is the first cause of pediatric acquired cardiovascular disease. The pathogenesis is complex and a viral trigger is suspected, as well as genetic susceptibility. Multiple studies around the world have shown a decrease in the incidence of Kawasaki disease and have hypothesized that the different sanitary measures enforced in each country during the pandemic period could be responsible to a certain extent. The aim of this study is to evaluate the effects of the COVID-19 pandemic on the disease's incidence, defining characteristics, coronary artery outcomes and management in a tertiary center in Switzerland. This study is a retrospective analysis of children who have been diagnosed with Kawasaki disease that compares clinical, laboratory, SARS-CoV-2 exposure, and echocardiographic data as well as treatments before (January 1st 2017 to February 24th 2020) and during (February 25th 2020 to December 31st 2022) the COVID-19 pandemic in Switzerland. Statistical significance of differences in the compared parameters was assessed. Of the 90 patients included, 31 belonged to the first group and 59 belonged to the second group. There was a statistically significant (p < 0.05) increase in incidence during the pandemic period (5.91/100,000 children) of 88% compared to the pre-pandemic period (3.14/100,000 children). A lesser seasonal variation was observed during the pandemic. 30% of the patients in the pandemic group had an exposure to SARS-CoV-2. There was no other notable difference in demographic factors, clinical presentation, coronary outcome or administered treatment. To the best of our knowledge, this is the first prolonged European study comparing Kawasaki disease before and during the COVID-19 pandemic. There was a significant increase in incidence in Kawasaki disease during the COVID-19 pandemic. In contrast, studies done in Japan, South Korea and the USA have shown a decrease in incidence. Differences in methodologies, genetics, ethnicities, environments, microbiome-altering behaviors, sanitary measures and SARS-CoV-2 spread are factors that should be considered. Further studies analyzing the differences between countries with increased incidence of Kawasaki disease could help better understand the relevance of such factors and provide more insight into the etiologies of this particular disease.

Suspected intracranial hypertension in COVID-19 patients with severe respiratory failure.

COVID-19 patients may exhibit neurological symptoms due to direct viral damage, systemic inflammatory syndrome, or treatment side effects. Mechanical ventilation in patients with severe respiratory failure often requires sedation and neuromuscular blockade, hindering thorough clinical examinations. This study aimed to investigate neurological involvement through clinical and noninvasive techniques and to detect signs of intracranial hypertension in these patients. We conducted a prospective observational study on mechanically ventilated COVID-19 adult patients admitted to our ICU, following standard of care protocols for ventilation and permissive hypercapnia. Data were collected at three time points: admission day (T1), day seven (T7), and day fourteen (T14). At each time point, patients underwent multimodal noninvasive neurological monitoring, including clinical examination, pupillary reactivity, transcranial color doppler of the middle cerebral artery (MCA), and optic nerve sheath diameter (ONSD) assessed via ultrasound (US). Head computer tomography (CT) was performed at T1 and T14. A limited subset of patients had a follow-up examination six months after ICU discharge. Seventy-nine patients were recruited; most were under deep sedation and neuromuscular blockade at T1. Pupillary size, symmetry, and reactivity were normal, as was the MCA mean velocity. However, ONSD, assessed by both US and CT, appeared enlarged, suggesting raised intracranial pressure (ICP). In a subgroup of 12 patients, increased minute ventilation was associated with a significant decrease in US-ONSD, corresponding to a drop in paCO2. At follow-up, twelve patients showed no long-term neurological sequelae, and US-ONSD was decreased in all of them. In this cohort, enlarged ONSD was detected during non-invasive neurological monitoring, suggesting a raised ICP, with hypercapnia playing a prominent role. Further studies are needed to explore ONSD behavior in other samples of mechanically ventilated, hypercapnic patients.

Cytokine release syndrome following COVID-19 infection during treatment with nivolumab for cancer of esophagogastric junction carcinoma: a case report and review

BackgroundCytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ failure, which is triggered by immunotherapy or certain infections. Immune checkpoint inhibitors rarely cause immune-related adverse event- cytokine release syndrome (irAE-CRS). This article presents a case report of irAE-CRS triggered by coronavirus disease 2019 (COVID-19).Case presentationA 60-year-old man with type 2 diabetes received nivolumab treatment for esophagogastric junction carcinoma and experienced two immune-related adverse events: hypothyroidism and skin disorder. Eleven days before his visit to our hospital, he had a fever and was diagnosed with COVID-19. Five days before his visit, he developed a fever again, along with general malaise, water soluble diarrhea, and myalgia of the extremities. On admission, the patient was in a state of multiple organ failure, and although the source of infection was unknown, a tentative diagnosis of septic shock was made. The patient's condition was unstable despite systemic management with antimicrobial agents, high-dose vasopressors, and intravenous fluids. We suspected CRS due to irAE (irAE-CRS) based on his history of nivolumab use. Steroid pulse therapy (methylprednisolone 1 g/day) was started, and the patient temporarily recovered. However, his respiratory condition worsened; consequently, he was placed on a ventilator and tocilizumab was added to the treatment. His muscle strength recovered to the point where he could live at home, and was subsequently discharged.ConclusionIn patients previously treated with immune checkpoint inhibitors, irAE-CRS should be considered as a differential diagnosis when multiple organ damage is observed in addition to inflammatory findings. It is recommended to start treatment with steroids; if the disease is refractory, other immunosuppressive therapies such as tocilizumab should be introduced as early as possible.

D4-Chip Reveals Impaired T Cell Function in Sepsis: Insights from Plasma Microenvironment Analysis and Mitochondrial Targeted Therapy.

Sepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear. We developed a novel method using the D4-Chip to assess sepsis T cell migration function. This microfluidic platform enabled precise analysis of migration function under controlled conditions. Additionally, We explored the impact of the plasma microenvironment on T cell behavior, along with the redox environment in sepsis, and assessed the potential efficacy of Mitoquinone mesylate (MitoQ), a mitochondrial-targeted drug. Our findings revealed impaired migration function in sepsis T cells compared to healthy controls. Interestingly, sepsis plasma enhanced the migration of healthy T cells, yet incubation with healthy plasma did not fully restore migration impairments in sepsis T cells. Subsequent investigations uncovered a significant increase in NADH/NAD+ levels in sepsis T cells, with healthy T cells exposed to various sepsis plasma conditions also showing elevated NADH/NAD+ levels. Importantly, MitoQ normalized abnormal intracellular NADH/NAD+ levels and enhanced the migration ability of T cells. Short-term incubation with sepsis plasma does not directly inhibit T cell migration but instead affects T cell function by disrupting the intracellular redox environment. Improving the intracellular redox environment of sepsis patients contributes to restoring impaired migration and proliferation, with MitoQ demonstrating therapeutic potential.

А COMPREHENSIVE STUDY OF PATIENTS WITH ISCHEMIC HEART DISEASE: AGE, GENDER, AND COMORBIDITY ASPECTS

The purpose of the study was to analyze the clinical characteristics, comorbid status, individual biochemical indicators, and systemic inflammation activity in patients with ischemic heart disease (IHD) depending on age, gender distribution, and diagnosis influence.Materials and methods. The study included 144 patients with IHD, who were divided into two groups – the main and the control. The main group comprised 120 patients with stable angina pectoris (SAP) II-III functional class (FC). The control group consisted of 24 patients with STEMI. All patients underwent a comprehensive examination: general clinical, anthropometric, laboratory (complete blood count, biochemical analysis), and instrumental (office blood pressure measurement, heart rate, and echocardiography). The comorbid profile of patients with IHD was assessed using the Charlson comorbidity index. The severity of systemic inflammation syndrome in the selected patient groups was assessed by the cellular composition of peripheral blood upon admission to the hospital, and based on the obtained data, the values of leukocyte inflammatory markers were calculated.Results. Patients in the main group were younger than those in the control group (54.78 ± 1.11 vs. 63.50 ± 1.82) (p&lt;0.001). A statistically significant predominance of men over women was found among the cohort of IHD patients (63.33% and 36.67%, respectively) (p&lt;0.001), with a tendency towards male predominance among patients with SAP II-III FC compared to those with STEMI (p = 0.074). Patients in the main group compared to those in the control group had significantly higher left ventricular ejection fraction (p&lt;0.001), systolic blood pressure (p&lt;0.001), and diastolic blood pressure (p=0.001). In the control group compared to the main group, more cases of patients with high levels of comorbidity were found (p&lt;0.001). Lower levels of creatinine, fibrinogen, prothrombin time, and glucose were observed in patients in the main group. Patients with SAP II-III FC compared to those with STEMI had lower levels of leukocyte inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR) (p&lt;0.001), systemic immune inflammation index (SII) (p=0.002), systemic inflammation response index (SIRI) (p=0.007), and aggregate index of systemic inflammation (AISI) (p=0.011).Conclusions. The study underscores the need for an individualized approach to each patient with ischemic heart disease, considering their age, gender, and comorbid characteristics, as well as laboratory peculiarities, to improve therapy outcomes and prevent complications.

Global Leadership Initiative on Malnutrition cachexia: an inflammation-first approach for the diagnosis of disease-related malnutrition.

The following article examines the rationale for an inflammation-first approach for diagnosing cachexia and how the current Global Leadership Initiative on Malnutrition (GLIM) framework may be adapted to facilitate this. Recently, the GLIM have published guidance on the measurement of inflammation in the context of cachexia, advocating that C-reactive protein (CRP) should be utilized for quantification. The inclusion of a systemic inflammatory biomarker for the diagnosis of cachexia questions whether it may be more aptly considered a systemic inflammatory syndrome. The current consensus of the GLIM is that cachexia is 'disease-related malnutrition with inflammation'. In line with this definition, the GLIM proposed a two-step diagnostic framework: screening for malnutrition using validated screening tools and then confirming the presence of disease-related malnutrition with phenotypic (nonvolitional weight loss, low BMI, and reduced muscle mass) and aetiologic criterion reduced food intake/assimilation, and inflammation or disease burden). The GLIM are to be commended for guidance on the measurement of systemic inflammation in their current proposal, given the relative importance to clinical outcomes in patients with cancer. However, the use of CRP is somewhat rudimentary and contrasts other cancer cachexia guidelines and contemporary clinical cancer research.

Maternal prenatal systemic inflammation indexes predicts premature neonatal respiratory distress syndrome

Neonatal respiratory distress syndrome (NRDS) is one of the leading causes of neonatal mortality in low-income countries. It is caused by a lack of surface-active substances in the lungs, and the maternal inflammatory response plays an important role in the formation of surface-active substances in the fetal lungs. We aimed to investigate the correlation between maternal prenatal systemic inflammatory indices and respiratory distress syndrome in preterm neonates. This is a retrospective case–control study that collected data from all patients who delivered between 28 and 36 weeks of gestation at Longhua District People's Hospital in Shenzhen City and whose infants were admitted to the neonatal unit, newborns with respiratory distress syndrome were in the experimental group (NRDS group), and newborns without NRDS were in the control group (non-NRDS group). To minimize the effect of confounders on the results, propensity score matching was performed on baseline characteristics. Totally, 524 patients were included (93 in the NRDS group and 431 in the non-NRDS group), and 71 matched pairs (142 patients). The neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI) and neutrophil lymphocyte to platelet ratio (NLPR) were higher in the NRDS group than in the non-NRDS group (p < 0.05). The ROC curves of NLR, dNLR, SII, SIRI, AISI and NLPR for the diagnosis of NRDS were plotted, and it was found that the combined diagnostic efficacy of these six systemic inflammatory markers was better (AUC: 0.643, P = 0.003). Patients were divided into two groups based on the cut-off values determined from the ROC curves, and analysis using binary regression models revealed that SII ≥ 1199.94 (OR, 2.554; 95% CI 1.245–5.239, P = 0.011) and NLPR ≥ 0.0239 (OR, 2.175; 95% CI 1.061–4.459, P = 0.034) were independent risk factors predicting NRDS. Maternal prenatal SII ≥ 1199.94 and NLPR ≥ 0.0239 are independent risk factors for NRDS, and clinicians may be used to prevent neonatal respiratory distress in advance to reduce the incidence of NRDS.

Multiplex array analysis of circulating cytokines and chemokines in COVID-19 patients during the first wave of the SARS-CoV-2 pandemic in Milan, Italy

BackgroundThe systemic inflammatory syndrome called “cytokine storm” has been described in COVID-19 pathogenesis, contributing to disease severity. The analysis of cytokine and chemokine levels in the blood of 21 SARS-CoV-2 positive patients throughout the phases of the pandemic has been studied to understand immune response dysregulation and identify potential disease biomarkers for new treatments. The present work reports the cytokine and chemokine levels in sera from a small cohort of individuals primarily infected with SARS-CoV-2 during the first wave of the COVID-19 pandemic in Milan (Italy).ResultsAmong the 27 cytokines and chemokines investigated, a significant higher expression of Interleukin-9 (IL-9), IP-10 (CXCL10), MCP-1 (CCL2) and RANTES (CCL-5) in infected patients compared to uninfected subjects was observed. When the change in cytokine/chemokine levels was monitored over time, from the hospitalization day to discharge, only IL-6 and IP-10 showed a significant decrease. Consistent with these findings, a significant negative correlation was observed between IP-10 and anti-Spike IgG antibodies in infected individuals. In contrast, IL-17 was positively correlated with the production of IgG against SARS-CoV-2.ConclusionsThe cytokine storm and the modulation of cytokine levels by SARS-CoV-2 infection are hallmarks of COVID-19. The current global immunity profile largely stems from widespread vaccination campaigns and previous infection exposures. Consequently, the immunological features and dynamic cytokine profiles of non-vaccinated and primarily-infected subjects reported here provide novel insights into the inflammatory immune landscape in the context of SARS-CoV-2 infection, and offer valuable knowledge for addressing future viral infections and the development of novel treatments.

Interleukin-1 blockade in patients with Wiskott-Aldrich syndrome: a retrospective multinational case series

AbstractUp to 70% of patients with Wiskott-Aldrich syndrome (WAS) develop autoimmune and inflammatory manifestations. Dysregulation of interleukin 1 (IL-1) may be involved in their pathogenesis, yet there is little evidence on treatment with anti–IL-1 agents in these patients. We conducted a multicenter retrospective analysis of 9 patients with WAS treated with anti–IL-1 agents (anakinra or canakinumab). All patients had prominent inflammatory manifestations, including systemic, cutaneous, articular, and intestinal symptoms; 3 patients presented with a severe systemic inflammatory syndrome since the first months of life. Corticosteroid therapy was associated with partial or no response, whereas treatment with anakinra or canakinumab resulted in prompt, often dramatic, responses in all patients, allowing bridging to gene therapy (4 patients) or hematopoietic stem cell transplantation (HSCT; 5 patients). Treatment was overall well tolerated. Low donor myeloid chimerism developed in 4 patients after HSCT and was associated with the appearance or the recurrence of inflammatory manifestations. A second HSCT was performed in 2 patients, achieving full-donor chimerism and resolution of inflammatory manifestation, whereas the other 2 patients were treated with prolonged therapy with anti–IL-1 agents. Our experience demonstrates that some inflammatory manifestations of WAS are dependent on IL-1 and respond well to its pharmacologic blockade.

Follow Up of Cardiovascular Affection in Covid-19 Pediatrics Survivors

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a rare complication of (SARS-CoV-2) infection. Presenting (4–6) weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation which is mostly due to post infection immune reaction. Aim of the Work to evaluate cardiac outcomes 6 months after initial presentation with MIS-C associated with cardiac affection. Patients and Methods This was a retrospective cohort study on 28 patients (19 boys &amp; 9 girls) who were diagnosed as multi system inflammatory syndrome in children (MIS-C) related to COVID19 six months ago at children`s hospital, Ain shams university from January 2021 to October 2021. All patients were subjected to the following: (demographic data, clinical signs and symptoms, laboratory investigations) in the acute phase (obtained from patient’s medical records) and at follow up after 6- months. Results in our study all patients fulfilled criteria of MIS-C presented with fever, shock or cardiac dysfunction and gastrointestinal symptoms in addition to conjunctivitis and skin rash. Our patients were presented with hypotension with mean systolic blood pressure (87) mmHg &amp; mean diastolic blood pressure (48) mmHg. Regarding symptoms: vomiting was seen in (60.7%), diarrhea in (32.1%), conjunctivitis in (82.1%) and cardiovascular abnormalities were seen in (100%) in the form of (myocardial dysfunction in (50%), coronary dilatation in (28.8%), valvular regurgitation in (100%) and pericardial effusion in (7.2%)). After 6 months there was significant improvement regarding vital signs. Regarding laboratory findings: at time of presentation most of the patients had high CRP, high troponin, and high CK-MB. On follow up after 6 months, all patients had normal values. Conclusion Our follow up study suggests that functional recovery and coronary outcomes are good in multisystem inflammatory syndrome in children.

Neutrophil-macrophage communication via extracellular vesicle transfer promotes itaconate accumulation and ameliorates cytokine storm syndrome.

Cytokine storm syndrome (CSS) is a life-threatening systemic inflammatory syndrome involving innate immune hyperactivity triggered by various therapies, infections, and autoimmune conditions. However, the potential interplay between innate immune cells is not fully understood. Here, using poly I:C and lipopolysaccharide (LPS)-induced cytokine storm models, a protective role of neutrophils through the modulation of macrophage activation was identified in a CSS model. Intravital imaging revealed neutrophil-derived extracellular vesicles (NDEVs) in the liver and spleen, which were captured by macrophages. NDEVs suppressed proinflammatory cytokine production by macrophages when cocultured in vitro or infused into CSS models. Metabolic profiling of macrophages treated with NDEV revealed elevated levels of the anti-inflammatory metabolite, itaconate, which is produced from cis-aconitate in the Krebs cycle by cis-aconitate decarboxylase (Acod1, encoded by Irg1). Irg1 in macrophages, but not in neutrophils, was critical for the NDEV-mediated anti-inflammatory effects. Mechanistically, NDEVs delivered miR-27a-3p, which suppressed the expression of Suclg1, the gene encoding the enzyme that metabolizes itaconate, thereby resulting in the accumulation of itaconate in macrophages. These findings demonstrated that neutrophil-to-macrophage communication mediated by extracellular vesicles is critical for promoting the anti-inflammatory reprogramming of macrophages in CSS and may have potential implications for the treatment of this fatal condition.

A histopathological analysis of extrapulmonary lesions in fatal coronavirus disease (COVID-19)

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues. Materials and methodsThe research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania. Tissues were processed and stained for histological examination. Differences in patients with and without diffuse alveolar damage (DAD) were evaluated. ResultsIn our study of 79 COVID-19 autopsies conducted on unvaccinated patients besides lung involvement, the patients had histological changes in at least two out of five (brain, heart, liver, kidney, and spleen) organs. Notable findings include hepatitis observed in 46.8 % of cases, 21.5 % with lobular hepatitis, and 41.8 % with liver steatosis. Additionally, 69.6 % exhibited acute tubular necrosis, and 55.7 % had varying degrees of splenic lymphocyte depletion. Almost 41 % of cases had pericardial effusion, 36.7 % myocarditis, 24.1 % myocardial infarction, and 12.7 % of cases had encephalitis. Acute tubular necrosis (78.6 %) was the most frequent histopathological finding observed in patients with DAD. Myocarditis was described in 45.9 % of the patients without DAD. DiscussionThe autopsy findings in our cohort of COVID-19 victims align with international scientific literature. Distinguishing viral-induced myocarditis, encephalitis, hepatitis, or systemic inflammatory syndrome remains challenging. ConclusionPost-mortem analysis identified lesions associated with SARS-CoV-2 in multiple organs, highlighting the systemic nature of the virus and emphasizing the need for continued research into organ-specific damage and long-term sequelae of COVID-19.

A Novel Drug Candidate for Sepsis Targeting Heparanase by Inhibiting Cytokine Storm.

Sepsis is an infection-triggered, rapidly progressive systemic inflammatory syndrome with a high mortality rate. Currently, there are no promising therapeutic strategies for managing this disease in the clinic. Heparanase plays a crucial role in the pathology of sepsis, and its inhibition can significantly relieve related symptoms. Here, a novel heparanase inhibitor CV122 is rationally designed and synthesized, and its therapeutic potential for sepsis with Lipopolysaccharide (LPS) and Cecal Ligation and Puncture (CLP)-induced sepsis mouse models are evaluated. It is found that CV122 potently inhibits heparanase activity in vitro, protects cell surface glycocalyx structure, and reduces the expression of adhesion molecules. In vivo, CV122 significantly reduces the systemic levels of proinflammatory cytokines, prevents organ damage, improves vitality, and efficiently protects mice from sepsis-induced death. Mechanistically, CV122 inhibits the activity of heparanase, reduces its expression in the lungs, and protects glycocalyx structure of lung tissue. It is also found that CV122 provides effective protection from organ damage and death caused by Crimean-Congo hemorrhagic fever virus (CCHFV) infection. These results suggest that CV122 is a potential drug candidate for sepsis therapy targeting heparanase by inhibiting cytokine storm.

Hemoadsorption Combined with Hemodialysis and the “Inflammation Mitigation Hypothesis”

ABSTRACT Clinical outcomes are still unsatisfactory in patients undergoing chronic maintenance dialysis. Signs and symptoms of uremic intoxication are often present even in presence of an adequate dialysis delivery. These along with cardiovascular and skeletal complications, have been correlated to the accumulation of inflammatory chemical mediators, beta-2 microglobulin (β2M), parathyroid hormone (PTH) and other middle to large molecular weight toxins that are insufficiently cleared by current dialysis techniques. Such condition determines a vicious loop where a subclinical status of inflammation causes a disruption of the immunological response affecting outcomes by accelerated atherosclerosis, anemia, and frequent infections. The overall picture can be described as a systemic inflammatory syndrome with simultaneous activation of the innate and the adaptive immunity. In such condition, new options and techniques are required to achieve a more effective blood purification and to correct the altered immuno-homeostasis. New efficient and biocompatible sorbents are today available (HA 130 Cartridge, Jafron Medical, Zhuhai, China) and they can be advantageously coupled in series with the hemodialyzer to perform hemoadsorption combined with hemodialysis (HA-HD). This technique has been already studied in at least two randomized trials demonstrating an effective improvement of clinical and biochemical outcomes. We have calculated the kinetics of β2M in a single session, in a series of three consecutive sessions of a week and in a period of three months using different frequencies of application (first month: Three sessions per week; second month: Two sessions per week; third month: One session per week). In the single session the reduction ratio was superior to other techniques such as hemodialysis (HD), high-flux hemodialysis (HFD) or hemodiafiltration (HDF). In the thrice weekly regime, the time average concentration (TAC) of β2M resulted inferior to HD and HDF. In the long period, a lower concentration of β2M was maintained even with a once-a-week regime. Considering the parallel reduction of inflammatory parameters, we could hypothesize that the enhanced removal of uremic toxins and chemical mediators led to a mitigation of the systemic inflammation with a progressive reduction in the generation of β2M. This “inflammation mitigation hypothesis (IMH)” supports the prescription of HA-HD once a week, possibly after a month of thrice weekly regime.

Assessing severity of COVID-19 and the development of multi system inflammatory syndrome in children (MIS-C) in pediatric patients with atopic disease.

Background: Research surrounding the coronavirus disease 2019 (COVID-19) pandemic and its impact on patients who are atopic has mainly focused on adults. After the delta variant showed increased rates of COVID-19 in children, the pediatric population needs to be assessed as well. Objective: The objective was to assess and report outcomes in patients with COVID-19 and with and without certain atopic diseases in our patient cohort at the University of Mississippi Medical Center. Methods: We conducted a retrospective review of patients by using a de-identified data base that allows querying via medical claims codes from the University of Mississippi Medical Center's Research Data Warehouse. We searched for patients who were COVID-19 positive and ages 0-21 years from January 1, 2020, to December 31, 2021. We then divided this population into two cohorts: an atopic population and a non-atopic population. The incidence of hospitalizations, intensive care unit (ICU) admissions, death, length of stay, inhaled corticosteroid prescription history, and the incidence of multi-system inflammatory syndrome in children (MIS-C) outcomes in the two populations were collected. Results: There were 5261 patients ages 0-21 years and with confirmed COVID-19. After exclusion criteria were applied, there were 1420 patients in the atopic cohort and 2525 patients in the non-atopic cohort. There were more hospitalizations and a longer length of stay in the atopic population. Mortality was equivalent in the atopic and non-atopic populations. There were more ICU admissions in the atopic population. There were 101 patients total with the diagnosis of MIS-C, and the incidence of MIS-C was similar in the atopic and non-atopic populations. There were more patients who were atopic on inhaled corticosteroid than were the patients who were non-atopic. Conclusion: This study sought to further elucidate whether asthma, atopic dermatitis, and allergic rhinitis in pediatric patients was associated with severe COVID-19. Our study showed increased hospitalizations, length of stay, and intensive care in the atopic population but similar outcomes in mortality and the development of MIS-C. Future longitudinal prospective studies are needed to assess the long-term effects on patient's atopic disease after COVID-19 infection.

The Effect of Implementing the Sepsis Early Goal-Directed Therapy (EGDT) Protocol on Patient Mortality in the Hospital ICU in Cairo, Egypt

Introduction: Sepsis is a life-threatening systemic inflammatory syndrome with a high mortality rate. Early goal-directed therapy (EGDT) is a structured therapy protocol that aims to improve tissue perfusion and oxygenation in sepsis patients.&#x0D; Methods: This retrospective observational study analyzed data on sepsis patients in the ICU of a Cairo hospital, Egypt (2020-2023). Patient mortality was compared before and after the implementation of the EGDT protocol.&#x0D; Results: Of the 220 sepsis patients, 120 were treated before and 100 after EGDT implementation. Patient mortality in the EGDT group was significantly lower (12% vs 25%, p&lt;0.05).&#x0D; Conclusion: Implementation of the EGDT protocol can reduce the mortality of sepsis patients in the hospital ICU in Cairo, Egypt.

NAT2 Gene Variants as a Provocative Factor for the Severe Course of COVID-19 Pneumonia in Ukrainian Patients

Background: Previous studies indicate a close relationship between the severity of COVID-19 and oxidative stress. N-acetyltransferase 2 (NAT2) is an enzyme that metabolizes a wide range of xenobiotics and plays an important role in the regulation of reactive oxygen species, consequently contributing to the development of oxidative stress. Aim: To determine the impact of NAT2 gene variants on the risk of developing and the progression of severe COVID-19-associated pneumonia in patients from the Poltava region of Ukraine. Methods: The study included 117 patients who were diagnosed with severe COVID-19 pneumonia and received treatment in the intensive care unit. The NAT2 gene variants were identified through the PCR-RFLP method. Results: The presence of the AA genotype of the A803G variant in patients with severe COVID-19 pneumonia is associated with an almost 3-fold reduction in the risk of lethal outcomes. The presence of the TT genotype of the C481T variant was associated with the need for artificial lung ventilation. Patients in the study group with a heterozygous GA genotype of the G590A variant demonstrated a notable rise in the risk of developing systemic inflammatory response syndrome and acute respiratory distress syndrome, with a nearly 2.5-fold and 3-fold increase, respectively. The G857A variant was not associated with the risk of developing the above-- mentioned complications in the examined patients. Conclusion: The obtained results suggested that the NAT2 gene variants might influence the incidence, course, and adverse consequences of COVID-19.

Maternal COVID-19 Infection Associated with Fetal Systemic Inflammatory Complications in COVID-19-Negative Neonates: A Case-Series.

This study aimed to examine fetal and neonatal inflammatory and neurologic complications associated with maternal coronavirus disease 2019 (COVID-19) infection. Case-series using a convenience sample of neonates cared for in a large referral-based children's hospital neonatal intensive care unit between September 2021 and May 2022. We identified seven neonates with exposure to maternal severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) and a presentation consistent with inflammatory complications. All had some degree of neurologic injury with neuroimaging findings including restricted diffusion indicating injury in the white matter, cortex, deep gray structures, and splenium of the corpus callosum as well as intracranial hemorrhage. In addition, many infants had cytopenia and abnormal coagulation studies. Placental pathology, when available, revealed inflammation, clot with calcifications, and hematomas with associated infarcts. Neonates born to mothers with SARS-CoV-2, even when negative for the virus themselves, may have complications consistent with a systemic inflammatory syndrome. Placental pathology as well as neurologic imaging in infants with neurologic findings may help to support this diagnosis. · A systemic inflammatory response may cause illness in babies born to mothers with a history of COVID-19.. · Inflammatory markers and placental pathology are helpful in supporting this diagnosis.. · Consider neuroimaging in infants of mothers with a history of COVID-19 with neurologic findings..

Coronavirus infection and systemic inflammatory reaction syndrome.

Aim: The purpose of this study was a clinical approbation of the Kometad drug (international non-proprietary name sodium colistimethate), an antibiotic from the polymyxin group in patients with severe course of confirmed сoronavirus infection in the intensive care unit of the Branch of the I. Zhekenova Municipal Clinical Infectious Diseases Hospital.. Materials and Methods: The methodology is based on both theoretical and empirical methods of scientific cognition. During the study, the features of the Coronavirus infection and the inflammatory reaction syndrome were considered, which became quite a big problem during the pandemic. Results: The main indications for the tested drug and the consequences of its use for one age group were also determined. Conclusions: The conclusion was made about the positive dynamics of the patients' health status, and recommendations were given for further research in this area. The practical significance of this study lies in the first clinical approbation of the Kometad drug, which can be used in medicine to reduce the severity of the systemic inflammatory reaction syndrome and improve the patient's health as a result of the disease of Coronavirus infection, after further clinical trials of the drug with different age groups of patients.

Systemic Inflammatory Polyarticular Gout Syndrome (SIPGS) with Unusual Cutaneous Manifestations: A Case Report

Systemic Inflammatory Polyarticular Gout Syndrome (SIPGS) with Unusual Cutaneous Manifestations: A Case Report