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1.
Journal of Intensive Medicine ; JOUR
Article in English | ScienceDirect | ID: covidwho-2105448

ABSTRACT

Microvascular alterations were first described in critically ill patients about 20 years ago. These alterations are characterized by a decrease in vascular density and presence of non-perfused capillaries close to well-perfused vessels. In addition, heterogeneity in microvascular perfusion is a key finding in sepsis. In this narrative review, we report our actual understanding of microvascular alterations, their role in the development of organ dysfunction, and the implications for outcome. Herein, we discuss the state of the potential therapeutic interventions and the potential impact of novel therapies. We also discuss how recent technologic development may affect the evaluation of microvascular perfusion.

2.
Thromb Res ; 220: 35-47, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2106047

ABSTRACT

Evidence of micro- and macro-thrombi in the arteries and veins of critically ill COVID-19 patients and in autopsies highlight the occurrence of COVID-19-associated coagulopathy (CAC). Clinical findings of critically ill COVID-19 patients point to various mechanisms for CAC; however, the definitive underlying cause is unclear. Multiple factors may contribute to the prothrombotic state in patients with COVID-19. Aberrant expression of tissue factor (TF), an initiator of the extrinsic coagulation pathway, leads to thrombotic complications during injury, inflammation, and infections. Clinical evidence suggests that TF-dependent coagulation activation likely plays a role in CAC. Multiple factors could trigger abnormal TF expression and coagulation activation in patients with severe COVID-19 infection. Proinflammatory cytokines that are highly elevated in COVID-19 (IL-1ß, IL-6 and TNF-α) are known induce TF expression on leukocytes (e.g. monocytes, macrophages) and non-immune cells (e.g. endothelium, epithelium) in other conditions. Antiphospholipid antibodies, TF-positive extracellular vesicles, pattern recognition receptor (PRR) pathways and complement activation are all candidate factors that could trigger TF-dependent procoagulant activity. In addition, coagulation factors, such as thrombin, may further potentiate the induction of TF via protease-activated receptors on cells. In this systematic review, with other viral infections, we discuss potential mechanisms and cell-type-specific expressions of TF during SARS-CoV-2 infection and its role in the development of CAC.

3.
Kidney Int ; 2022 Nov 09.
Article in English | MEDLINE | ID: covidwho-2105523

ABSTRACT

The most common cause of acute kidney injury (AKI) in critically ill patients is sepsis. Kidney macrophages consist of both F4/80hi and CD11bhi cells. The role of macrophage subpopulations in septic AKI pathogenesis remains unclear. As F4/80hi macrophages are reported to contribute to immunomodulation following injury, we hypothesized that selective depletion of F4/80hi macrophages would worsen septic AKI. F4/80hi macrophages were depleted via diphtheria toxin injection in CD11cCre(+)/CX3CR1dtr/wt (F4/80 MKO mice) compared to CD11cCre(-)/CX3CR1dtr/wt (F4/80 MWT) mice. F4/80 MWT and F4/80 MKO mice were subjected to sham or cecal ligation and puncture to induce sepsis. Compared to F4/80 MWT mice, F4/80 MKO mice displayed worsened septic AKI at 24 hours as measured by serum creatinine and histologic injury scoring. Kidneys from F4/80 MKO mice elaborated higher kidney interleukin-6 levels. Mechanistically, single cell RNA sequencing identified a macrophage-endothelial cell immunoregulatory axis that underlies interleukin-6 expression. F4/80hi macrophages expressed interleukin-1 receptor antagonist and limited interleukin-6 expression in endothelial cells. In turn, anti-interleukin-6 therapy ameliorated septic AKI in F4/80 MKO mice. Thus, F4/80hi macrophages express interleukin-1 receptor antagonist and constrain interleukin-6 generation from endothelial cells to limit septic AKI, representing a targetable cellular crosstalk in septic AKI. These findings are particularly relevant owing to the efficacy of anti-interleukin-6 therapies during COVID-19 infection, a disease associated with high rates of AKI and endothelial dysfunction.

4.
Immunobiology ; 227(6): 152288, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-2105124

ABSTRACT

The clinical presentation of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges between mild respiratory symptoms and a severe disease that shares many of the features of sepsis. Sepsis is a deregulated response to infection that causes life-threatening organ failure. During sepsis, the intestinal epithelial cells are affected, causing an increase in intestinal permeability and allowing microbial translocation from the intestine to the circulation, which exacerbates the inflammatory response. Here we studied patients with moderate, severe and critical COVID-19 by measuring a panel of molecules representative of the innate and adaptive immune responses to SARS-CoV-2, which also reflect the presence of systemic inflammation and the state of the intestinal barrier. We found that non-surviving COVID-19 patients had higher levels of low-affinity anti-RBD IgA antibodies than surviving patients, which may be a response to increased microbial translocation. We identified sFas and granulysin, in addition to IL-6 and IL-10, as possible early biomarkers with high sensitivity (>73 %) and specificity (>51 %) to discriminate between surviving and non-surviving COVID-19 patients. Finally, we found that the microbial metabolite d-lactate and the tight junction regulator zonulin were increased in the serum of patients with severe COVID-19 and in COVID-19 patients with secondary infections, suggesting that increased intestinal permeability may be a source of secondary infections in these patients. COVID-19 patients with secondary infections had higher disease severity and mortality than patients without these infections, indicating that intestinal permeability markers could provide complementary information to the serum cytokines for the early identification of COVID-19 patients with a high risk of a fatal outcome.

6.
Scand J Trauma Resusc Emerg Med ; 29(1): 145, 2021 Oct 03.
Article in English | MEDLINE | ID: covidwho-2098399

ABSTRACT

BACKGROUND: Sepsis is a life-threatening organ dysfunction and a major healthcare burden worldwide. Although sepsis is a medical emergency that requires immediate management, screening for the occurrence of sepsis is difficult. Herein, we propose a deep learning-based model (DLM) for screening sepsis using electrocardiography (ECG). METHODS: This retrospective cohort study included 46,017 patients who were admitted to two hospitals. A total of 1,548 and 639 patients had sepsis and septic shock, respectively. The DLM was developed using 73,727 ECGs from 18,142 patients, and internal validation was conducted using 7774 ECGs from 7,774 patients. Furthermore, we conducted an external validation with 20,101 ECGs from 20,101 patients from another hospital to verify the applicability of the DLM across centers. RESULTS: During the internal and external validations, the area under the receiver operating characteristic curve (AUC) of the DLM using 12-lead ECG was 0.901 (95% confidence interval, 0.882-0.920) and 0.863 (0.846-0.879), respectively, for screening sepsis and 0.906 (95% confidence interval (CI), 0.877-0.936) and 0.899 (95% CI, 0.872-0.925), respectively, for detecting septic shock. The AUC of the DLM for detecting sepsis using 6-lead and single-lead ECGs was 0.845-0.882. A sensitivity map revealed that the QRS complex and T waves were associated with sepsis. Subgroup analysis was conducted using ECGs from 4,609 patients who were admitted with an infectious disease, and the AUC of the DLM for predicting in-hospital mortality was 0.817 (0.793-0.840). There was a significant difference in the prediction score of DLM using ECG according to the presence of infection in the validation dataset (0.277 vs. 0.574, p < 0.001), including severe acute respiratory syndrome coronavirus 2 (0.260 vs. 0.725, p = 0.018). CONCLUSIONS: The DLM delivered reasonable performance for sepsis screening using 12-, 6-, and single-lead ECGs. The results suggest that sepsis can be screened using not only conventional ECG devices but also diverse life-type ECG machines employing the DLM, thereby preventing irreversible disease progression and mortality.


Subject(s)
COVID-19 , Deep Learning , Sepsis , Electrocardiography , Humans , Retrospective Studies , SARS-CoV-2 , Sepsis/diagnosis
7.
Front Med (Lausanne) ; 9: 972040, 2022.
Article in English | MEDLINE | ID: covidwho-2089858

ABSTRACT

Sepsis is a clinical syndrome characterized by a dysregulated response to infection. It represents a leading cause of mortality in ICU patients worldwide. Although sepsis is in the point of interest of research for several decades, its clinical management and patient survival are improving slowly. Monitoring of the biomarkers and their combinations could help in early diagnosis, estimation of prognosis and patient's stratification and response to the treatment. Circulating soluble endoglin (sEng) is the cleaved extracellular part of transmembrane glycoprotein endoglin. As a biomarker, sEng has been tested in several pathologic conditions where its elevation was associated with endothelial dysfunction. In this study we have tested the ability of sEng to predict mortality and its correlation with other clinical characteristics in the cohort of septic shock patients (n = 37) and patients with severe COVID-19 (n = 40). In patients with COVID-19 sEng did not predict mortality or correlate with markers of organ dysfunction. In contrast, in septic shock the level of sEng was significantly higher in patients with early mortality (p = 0.019; AUC = 0.801). Moreover, sEng levels correlated with signs of circulatory failure (required dose of noradrenalin and lactate levels; p = 0.002 and 0.016, respectively). The predominant clinical problem in patients with COVID-19 was ARDS, and although they often showed signs of other organ dysfunction, circulatory failure was exceptional. This potentially explains the difference between sEng levels in COVID-19 and septic shock. In conclusion, we have confirmed that sEng may reflect the extent of the circulatory failure in septic shock patients and thus could be potentially used for the early identification of patients with the highest degree of endothelial dysfunction who would benefit from endothelium-targeted individualized therapy.

8.
J Control Release ; 352: 931-945, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2086390

ABSTRACT

COVID-19 acquired symptoms have affected the worldwide population and increased the load of Intensive care unit (ICU) patient admissions. A large number of patients admitted to ICU end with a deadly fate of mortality. A high mortality rate of patients was reported with hospital-acquired septic shock that leads to multiple organ failures and ultimately ends with death. The patients who overcome this septic shock suffer from morbidity that also affects their caretakers. To overcome these situations, scientists are exploring progressive theragnostic techniques with advanced techniques based on biosensors, biomarkers, biozymes, vesicles, and others. These advanced techniques pave the novel way for early detection of sepsis-associated symptoms and timely treatment with appropriate antibiotics and immunomodulators and prevent the undue effect on other parts of the body. There are other techniques like externally modulated electric-based devices working on the principle of piezoelectric mechanism that not only sense the endotoxin levels but also target them with a loaded antibiotic to neutralize the onset of inflammatory response. Recently researchers have developed a lipopolysaccharide (LPS) neutralizing cartridge that not only senses the LPS but also appropriately neutralizes with dual mechanistic insights of antibiotic and anti-inflammatory effects. This review will highlight recent developments in the new nanotechnology-based approaches for the diagnosis and therapeutics of sepsis that is responsible for the high number of deaths of patients suffering from this critical disease.

10.
Int J Mol Sci ; 23(20)2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2082320

ABSTRACT

Recent research has contributed significantly to our understanding of the pathogenesis of acute disseminated intravascular coagulation. COVID-19 can be considered as a new underlying condition of disseminated intravascular coagulation. In this narrative review, current evidence is presented regarding biomarker differences between sepsis-induced and COVID-19-associated coagulopathies, supporting the importance of acquired antithrombin deficiency in the early differential diagnosis of septic coagulopathy and its potential impact on treatment with endogenous anticoagulants. Establishing new scoring systems for septic coagulopathy in combination with endogenous anticoagulant biomarker activities may allow for the identification of those in the heterogeneous population of sepsis patients who are more likely to benefit from targeted specific treatment interventions.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Disseminated Intravascular Coagulation , Sepsis , Humans , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Antithrombins/therapeutic use , COVID-19/complications , Anticoagulants/therapeutic use , Anticoagulants/pharmacology , Blood Coagulation Disorders/complications , Sepsis/complications , Antithrombin III , Biomarkers
11.
Cureus ; 14(9): e29528, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2072217

ABSTRACT

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.

12.
Research and Practice in Thrombosis and Haemostasis ; 6(7), 2022.
Article in English | Web of Science | ID: covidwho-2068582

ABSTRACT

Infectious and inflammatory stimuli induce the release of neutrophil extracellular traps (NETs), webs of cell-free (cf) DNA complexed with histones and antimicrobial proteins, that capture and kill pathogens. Despite their protective role in the initial stages of sepsis, excessive NET release accompanied by NET degradation, leads to the release of NET degradation products (NDPs), including cfDNA, histones, and myeloperoxidase that injure the microvasculature. Murine studies have shown that clearance or neutralization of NDPs improves outcomes, demonstrating that NETs have a causal link to disease and are not merely biomarkers. Recently, elevated NDPs have been associated with disease severity in sepsis and coronavirus disease 2019, raising further interest in targeting NETs. Many propose eliminating NETs, either by preventing their release, or by degrading them. However, NET inhibition may impede the innate immune response and is difficult to achieve in rapid-onset conditions such as sepsis. On the other hand, approaches that accelerate NET degradation have met with mixed results in murine studies, raising the concern that this strategy may liberate NET-captured pathogens while increasing circulating levels of harmful NDPs. Alternative NET-directed strategies include therapies that neutralize, sequester, or remove NDPs from the circulation. Others propose modifying released NETs to decrease their capacity to induce collateral tissue damage while enhancing their ability to capture microorganisms. Synthetic NETs have also been designed to combat antibiotic-resistant organisms. Although it is still in its infancy, the field of NET-targeted therapeutics is advancing rapidly and may soon find application in the treatment of sepsis and other inflammatory disorders.

13.
Acta Medica Peruana ; 39(2):151-165, 2022.
Article in Spanish | EMBASE | ID: covidwho-2067671

ABSTRACT

The Janus-Kinase signal transducer and the transcription activation pathway known as JAK / STAT is a major signaling pathway for the transduction of information in many inflammatory cytokines involved during sepsis. The JAK / STAT pathway has been shown to be strongly related to multiorgan failure, and many cytokines can exert their biological effects through this pathway. In recent years, considerable progress has been made in understanding functions of this complex;however, its role in sepsis as a therapeutic target remains under experimentation. This review describes the specific functions of the JAK / STAT pathway, its role in sepsis, and presents a translational approach to the therapeutic perspective aiming to inhibit this signaling pathway during sepsis and its interaction with inflammatory diseases such as COVID-19. Copyright © 2022 by Begell House, Inc.

14.
Cells ; 11(19)2022 Sep 27.
Article in English | MEDLINE | ID: covidwho-2065727

ABSTRACT

Clinical success of Toll-Like receptor-4 (TLR-4) antagonists in sepsis therapy has thus far been lacking. As inhibition of a receptor can only be useful if the receptor is active, stratification of patients with active TLR-4 would be desirable. Our aim was to establish an assay to quantify phosphorylated TLR-4 using the proximity ligation assay (PLA). HEK293 TLR4/MD2/CD14 as well as THP-1 cells were stimulated with LPS and the activation of TLR-4 was measured using the PLA. Furthermore, peripheral blood mononuclear cells (PBMCs) from 25 sepsis patients were used to show the feasibility of this assay in clinical material. Activation of TLR-4 in these samples was compared to the PBMCs of 11 healthy individuals. We could show a transient activation of TLR-4 in both cell lines. Five min after the LPS stimulation, the signal increased 6.7-fold in the HEK293 cells and 4.3-fold in the THP-1 cells. The assay also worked well in the PBMCs of septic patients. Phosphorylation of TLR-4 at study inclusion was 2.9 times higher in septic patients compared to healthy volunteers. To conclude, we established a diagnostic assay that is able to quantify the phosphorylation of TLR-4 in cell culture and in clinical samples of sepsis patients. This makes large-scale stratification of sepsis patients for their TLR-4 activation status possible.


Subject(s)
Sepsis , Toll-Like Receptor 4/metabolism , HEK293 Cells , Humans , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology
15.
Gut ; 71(Suppl 3):A83, 2022.
Article in English | ProQuest Central | ID: covidwho-2064233

ABSTRACT

P69 Table 1Demographic and transplant data for all 14 prioritised patientsPatient/Sex Centre Age at registration (yrs) Primary liver disease Registered prior to Prioritisation Indication of Prioritization LT Waiting time on prioritised tier/Time on list prior to prioritisation 1/M 1 0 CDG Yes Acute decompensation with presence of encephalopathy Yes/LLS 5/27 2/M 2 1 Cryptogenic Cirrhosis Yes CLD with nodular lesions s/o HCC Yes/LLS 16/48 3/F 1 15 AILD Yes Chronic rejection Yes/whole liver 3/4 4/M 2 0 Biliary Atresia Yes PTLD/HAT/Sepsis Yes/LLS 14/71 5/F 2 4 IFALD No Coagulopathy with active bleeding/Renal impairment Yes/LLS 15/820 6/F 2 0 Biliary Atresia Yes Acute decompensation due to portal hypertension Yes/LLS 37/405 7/M 2 10 NSC Yes Decompensated chronic liver disease/Renal impairment Yes/reduced R lobe 4/7 8/M 3 8 PFIC3 Yes Acute decompensation of Chronic liver disease Yes/LLS 6/51 9/F 1 0 Other (Hepatoblastoma) Intestinal Tx prioritized Acute decompensation of Chronic liver disease Yes/LLS 11/ 10/F 2 0 Biliary atresia Yes Decompensated Chronic Liver Disease with Severe Coagulopathy Yes/LLS 10/120 11/M 1 0 Biliary atresia (Hepatoblastoma) Yes Acute decompensation of Chronic liver disease Yes/LLS 9/4 12/F 3 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Yes/LLS 12/323 13/F 1 17 Hepatic Artery thrombosis Yes Hepatic Artery thrombosis Yes/whole liver 2/ 14/F 2 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Suspended 12/65 PFIC3;Progressive Familial Intrahepatic Cholestasis type 3, LT;Liver transplantation, HCC;Hepatocellular Carcinoma NSC;Neonatal Sclerosing Cholangitis, CDG;Congenital Disorder of Glycosylation, AILD;Autoimmune Liver Disease, IFALD;Intestinal Failure Associated Liver Disease,PTLD;Center 1-Kings;Center2-Birmingham;Center3-Leeds.ConclusionThe national paediatric prioritization tier, introduced during the COVID19 pandemic, has been a pivotal initiative for the UK paediatric LT program, showcasing national collaboration. All patients underwent a LT successfully within a short time from prioritization with 100% patient and graft survival. The intention is to maintain this prioritized paediatric tier beyond the pandemic.

16.
Archives of Disease in Childhood ; 107(Supplement 2):A359-A360, 2022.
Article in English | EMBASE | ID: covidwho-2064045

ABSTRACT

Aims To describe a case of 3 weeks old neonate presenting with severe pulmonary hemorrhage due to COVID-19 infection and its outcome. Methods We report an interesting case of pulmonary hemorrhage presenting at a young age of 3 weeks, in a previously healthy neonate who was infected with COVID-19 virus;Literature review and investigation results are included. This is a 3-week-old female, a product of full-term pregnancy and an uneventful perinatal course. She was admitted from the emergency department initially as a case of late neonatal sepsis, where a full septic workup was done. Her presenting complaints were low-grade fever and a blocked nose for one day. She was hemodynamically stable in the emergency department except for tachycardia secondary to fever, which improved once the fever was controlled. Her initial blood workup, including blood gas and CSF study, was reassuring (table 1a). Her COVID PCR was positive with a CT value of 17.77. She was treated with IV antibiotics and supportive management. Later that day, the patient developed cardiopulmonary arrest, CPR was initiated, and the patient was intubated. The patient was found to have pulmonary hemorrhage as evident by the fresh blood coming out of the endotracheal tube and the chest X-Ray findings of ground-glass opacities and dense consolidation (figure 1). After initial brief stabilization, the patient started deteriorating requiring escalation of respiratory support to HFOV. The patient continued to deteriorate and developed bilateral pneumothorax requiring bilateral chest tube insertion. After chest tube insertion, there was a mild transient improvement in oxygenation. The patient was put on the maximum ventilatory settings, but she kept having frequent desaturation, requiring frequent manual bag to tube ventilation. Later, she started developing progressive hypotension, that required support with maximum doses of inotropes. Her urine output started decreasing, for which frusemide were started with no response. Blood investigations showed severe DIC picture (table 1b and 1c). She was empirically covered with Meropenem and Vancomycin along with Remdesivir and Dexamethasone for COVID 19 pneumonia. Eventually, the child developed progressive desaturation, hypotension, and poor perfusion. Shortly after that, she developed cardiac arrest and was declared dead. Results The clinical picture of COVID 19 infection is more indistinct in children than in adults, with the most common symptoms being fever, cough, dyspnea, and malaise. In the few published cases of COVID-19 in the neonate, the presentation was that of late neonatal sepsis;interestingly, the lung involvement was not described as frequently as in older age groups. Pulmonary hemorrhage has been reported in adults but rarely in children. Some reports in adults suggested that patients with COVID infection had an increased inflammatory state that led to the development of vasculitis and pulmonary hemorrhage. Up to our knowledge, this is the youngest age at which a patient with COVID-19 infection developed pulmonary hemorrhage with no other underlying cause of it. Conclusion While many of the cases of COVID infection in children are mild, fatal complications like pulmonary hemorrhage can be present. Adding new challenges to the management of this viral infection.

17.
Archives of Disease in Childhood ; 107(Supplement 2):A207, 2022.
Article in English | EMBASE | ID: covidwho-2064029

ABSTRACT

Aims Paediatric populations are generally considered to be at a lower risk of mortality from COVID-19 infection compared with adult populations. Regardless, a notable number of deaths from COVID-19 have been reported in paediatric populations. Therefore, the purpose of our work was to conduct a scoping review of the literature to assess the risk factors for COVID-19 mortality among paediatric populations. Methods Our review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). Searches were performed in PubMed, Scopus, medRxiv, and WHO Coronavirus Database. There were no restrictions placed for searches based on date. Papers that were written in English, included at least one paediatric death from COVID-19, and described at least one risk factor for the death and/or clinical presentation of the child(ren) were eligible for inclusion. The paediatric population was defined as children aged 18 years and younger. Results Searches generated a total of 5828 papers and, of those, 75 were eligible for inclusion. There was a pooled total of 876 paediatric deaths. Significant risk factors for paediatric mortality included having co-infection of other pathogens, and at least one comorbidity;the comorbidities most frequently associated with mortality were malignancies, heart conditions, kidney disease, and genetic disorders such as Down Syndrome. The development of Paediatric Multisystem Inflammatory Syndrome (PMIS) was also consistently demonstrated to be a risk factor. Common clinical complications associated with paediatric COVID-19 infection resulting in mortality were sepsis, acute respiratory distress syndrome (ARDS), and acute kidney injury (AKI). Conclusion Our review has highlighted prominent risk factors for mortality from COVID-19 amongst paediatric populations. It is vital to consider the risk factors in order to assist prognostication and clinical decisions for severe paediatric infections of COVID-19. Our findings also highlight the importance of COVID-19 vaccination in paediatric populations.

18.
Archives of Disease in Childhood ; 107(Supplement 2):A203-A204, 2022.
Article in English | EMBASE | ID: covidwho-2064028

ABSTRACT

Aims Multisystem inflammatory syndrome in children (MIS-C) secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected not only the older children, adolescents and adults but also infants, more so during the second wave of the global pandemic. Thus, this study was done to describe the profile of infants presenting with multisystem inflammatory syndrome (MIS) with the aim to alert clinicians regarding the need for its early diagnosis and timely management in this vulnerable age group to prevent the morbidity, mortality and long term complications associated with MIS-C. Methods All sequentially admitted infants hospitalized during a period of 6months from,who fulfilled the WHO/CDC/RPCH criteria for MIS-C were included in the study. The data was recorded in a semi-structured pre-tested self-designed proforma regarding the demographic profile, presenting symptoms, clinical signs, laboratory parameters and treatment received. The data was analysed using appropriate statistical tools. Results A total of 19 infants were studied. Of these, 68.3% (13) had an evidence of recent COVID-19 infection. The median age of presentation was 2 months. The male:female ratio was 1.1:1. The most common presenting symptoms were fever (68.4%), gastrointestinal complaints (63.1%) and edema (36.8%) (figure 1). Other predominant signs were shock (78.9%), myocarditis (52.6%) and neurological complaints (26.3%). Incomplete Kawasaki disease was present in 21% patients. Elevated CRP, ferritin, D-Dimer, NT pro BNP and reduced fibrinogen were markers of severe illness. All subjects received IVIG (100%), 31.5% received a second dose of IVIG and 63.1% received pulse intravenous methylprednisolone. (table 1) A total of 5(26.3%) died as a result of the disease process. Conclusion MIS-C in infants is usually under-diagnosed and under-reported due to the considerable overlap between sepsis and MIS-C especially due to the higher incidence of sepsis in developing countries. The spectrum of this illness can be varied and is different from the overt clinical signs seen in older children and adolescents. Thus, these investigations should be done early in the course for optimal therapy with immunomodulators and favourable outcome.. (Figure Presented).

19.
Archives of Disease in Childhood ; 107(Supplement 2):A2, 2022.
Article in English | EMBASE | ID: covidwho-2064008

ABSTRACT

Aims Medical simulation is a well-recognised tool in reducing anxiety and improving clinical confidence and competence in medical students (1). During the coronavirus pandemic a large proportion of medical students studied virtually with >23.5% of students studying online for >15 hours a week (2), reducing clinical exposure. We appreciate that this may affect confidence in clinical assessment. Studies have shown repeated exposure to simulation is important in building and retaining confidence in medical students (3). We developed a robust simulation programme at a children's teaching hospital for 20 fourth year undergraduate medical students from one higher education institution, aiming to establish whether simulation could improve students' confidence in assessing an unwell child. Methods A seven week programme was developed providing students up to four simulation sessions in total. All students acted as both participants and active observers. We surveyed 20 students on their confidence in assessing a child before and after the implementation of the programme, running alongside their paediatric rotation. The students divided their roles as junior doctors, nurses, and healthcare assistants. We discussed these roles in detail so they could appreciate the interprofessional involvement in such scenarios. Each scenario involved an introduction to simulation, introduction to the equipment, a pre-brief of the scenario and proposed methods of management, a ten minute acute paediatric scenario, and a debrief as per the diamond debrief model (figure 1). Scenarios covered included bronchiolitis, sepsis, acute asthma, and anaphylaxis;providing a range of acute paediatrics. APLS guidelines, the BNFC, and local protocols were available;as well as senior support if called. All teachers were trained in simulation teaching and debriefing. We collected qualitative and quantitative feedback through anonymous surveys. Of note, for 89% of students this programme was their first experience of paediatric simulation. Given the limited exposure of the students to simulation, the first session had a dedicated 10 minute talk on the concepts of simulation including the 'suspension of disbelief '. Results Initially, students felt 'scared', 'stressed', 'anxious' and 'inexperienced' about assessing a sick child and 'intimidated', 'terrified' and 'nervous' about simulation. Following the programme (see figure 2): 65% of students felt 'somewhat confident' in examining children. 94.7% of students feel that simulating acute scenarios will benefit their practice. 90% of students felt more confident about future simulation. Students appreciated the opportunity to 'practice making decisions'. One student commented that this is 'hard to come by on wards as you're often just observing rather than assessing'. Conclusion This seven-week paediatric simulation programme improved student confidence in examining and assessing an unwell child, in addition to improving confidence for future simulation. Alanazi et al proposed five best practice measures of simulation in education: study design, debriefing, integration of interprofessional education values, outcome measures, and student satisfaction. All were practised in this programme. Through ensuring a psychologically safe workspace, with appropriate resources and trained teachers, we believe we have created a non-intimidating and encouraging simulation environment. We look to provide virtual alternatives such as online video based interactive simulation should social distancing affect simulation teaching further.

20.
American Journal of Transplantation ; 22(Supplement 3):664, 2022.
Article in English | EMBASE | ID: covidwho-2063499

ABSTRACT

Purpose: Transplantation of kidneys from donors with active SARS-CoV-2 infection is uncommon due to concerns about the risk of viral transmission and kidney quality. To date, there is no conclusive data that viral transmission from extra-pulmonary solid organ transplant is a possibility. Given the prevalence of SARS-CoV-2 infections in potential donors, the shortage of kidneys available for transplantation and the low risk of viral transmission, we developed a clinical protocol for accepting kidneys from donors with active SARS-CoV-2 infection and preserved kidney function. Method(s): Retrospective chart review of 5 kidney transplant recipients from 4 deceased donors with severe SARS-CoV-2 infection. Donor and recipient characteristics are reported using descriptive characteristics. Result(s): Donor creatinine ranged from 0.51 to 0.60 mg/dL and KDPI ranged from 14% to 52%. Three of the 5 kidneys came from donation after circulatory death donors. All recipients were fully vaccinated, and 4/5 received post-exposure prophylactic monoclonal antibody treatment. 3 recipients had delayed graft function but were off of dialysis by postoperative day 6 or 8. 3 recipients were readmitted, one for fluid overload and mild rejection on two different occasions, one for hypotension from dehydration and one for sepsis secondary to an aspiration pneumonia. The latter recipient subsequently died with a functioning graft secondary to a severe bacterial infection. This recipient was also found to have a femoral DVT during readmission on the contralateral side to the kidney graft. At 30 days post-transplant, no recipients displayed signs or symptoms of SARS-CoV-2 infection and the three who were readmitted tested negative for SARS-CoV-2 via nasopharyngeal swab. All had a creatinine less than 2 at the most recent follow up. Conclusion(s): Our findings suggest that kidney grafts from donors with severe SARSCoV- 2 infection but preserved kidney function can be safely used and have good early outcomes. However, more research is needed to determine the safety and long term outcomes of kidney transplantation from donors with severe COVID-19 pneumonia.

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