Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19.
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ABSTRACT:
SUBMITTER: Basalely A
PROVIDER: S-EPMC7927648 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multisystem Inflammatory Syndrome in Children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by SARS-CoV-2 antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism, distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that the hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature.
2022-11-05 | GSE217370 | GEO
Project description:Multisystem Inflammatory Syndrome in Children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory systemic illness characterized by SARS-CoV-2 antigenemia, cytokine storm and immune dysregulation; however, the role of the neutrophil has yet to be defined. In adults with severe COVID-19, neutrophil activation has been shown to be central to overactive inflammatory responses and complications. Thus, we sought to define neutrophil activation in children with MIS-C and acute COVID-19. We collected samples from 141 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 67 pediatric controls. We found that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism, which is markedly different than the neutrophil interferon-stimulated gene (ISG) response observed in pediatric patients during acute SARS-CoV-2 infection. Moreover, we identified signatures of neutrophil activation and degranulation with high levels of spontaneous neutrophil extracellular trap (NET) formation in neutrophils isolated from fresh whole blood of MIS-C patients. Mechanistically, we determined that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Overall, our findings suggest that the hyperinflammatory presentation of MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia through uncontrolled neutrophil activation and NET release in the vasculature.One sentence summaryCirculating SARS-CoV-2 antigen:antibody immune complexes in Multisystem Inflammatory Syndrome in Children (MIS-C) drive hyperinflammatory and coagulopathic neutrophil extracellular trap (NET) formation and neutrophil activation pathways, providing insight into disease pathology and establishing a divergence from neutrophil signaling seen in acute pediatric COVID-19.
| S-EPMC8722589 | biostudies-literature
Project description:The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis.
| S-EPMC7229463 | biostudies-literature
Project description:Rationale & objectiveOutcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) are not well understood. The goal of this study was to investigate the survival and kidney outcomes of these patients.Study designRetrospective cohort study.Setting & participantsPatients (aged≥18 years) hospitalized with COVID-19 at 13 hospitals in metropolitan New York between March 1, 2020, and April 27, 2020, followed up until hospital discharge.ExposureAKI.OutcomesPrimary outcome: in-hospital death.Secondary outcomesrequiring dialysis at discharge, recovery of kidney function.Analytical approachUnivariable and multivariable time-to-event analysis and logistic regression.ResultsAmong 9,657 patients admitted with COVID-19, the AKI incidence rate was 38.4/1,000 patient-days. Incidence rates of in-hospital death among patients without AKI, with AKI not requiring dialysis (AKI stages 1-3), and with AKI receiving dialysis (AKI 3D) were 10.8, 31.1, and 37.5/1,000 patient-days, respectively. Taking those without AKI as the reference group, we observed greater risks for in-hospital death for patients with AKI 1-3 and AKI 3D (HRs of 5.6 [95% CI, 5.0-6.3] and 11.3 [95% CI, 9.6-13.1], respectively). After adjusting for demographics, comorbid conditions, and illness severity, the risk for death remained higher among those with AKI 1-3 (adjusted HR, 3.4 [95% CI, 3.0-3.9]) and AKI 3D (adjusted HR, 6.4 [95% CI, 5.5-7.6]) compared with those without AKI. Among patients with AKI 1-3 who survived, 74.1% achieved kidney recovery by the time of discharge. Among those with AKI 3D who survived, 30.6% remained on dialysis at discharge, and prehospitalization chronic kidney disease was the only independent risk factor associated with needing dialysis at discharge (adjusted OR, 9.3 [95% CI, 2.3-37.8]).LimitationsObservational retrospective study, limited to the NY metropolitan area during the peak of the COVID-19 pandemic.ConclusionsAKI in hospitalized patients with COVID-19 was associated with significant risk for death.
| S-EPMC7833189 | biostudies-literature
Project description:The initial report of the multisystem inflammatory syndrome in children (MIS-C) was from the UK in April 2020; since then, cases have been reported worldwide. Renal involvement has been seen commonly, ranging from 10% to 46%. Kidney involvement following severe acute respiratory syndrome coronavirus 2 infection in children with MIS-C is more common than initially thought and is associated with higher morbidity and mortality. There are several reports of a direct viral tropism of coronavirus disease 2019 and MIS-C-associated renal damage. This study's objective was to systematically review the current understanding of kidney involvement in children suffering from MIS-C. Based on our systemic literature search, 19 studies have either partially or fully discussed kidney involvement in MIS-C patients. Furthermore, we discuss the multifactorial pathogenesis contributing to acute kidney injury (AKI) development in MIS-C. The current review gives a pediatric nephrologist's perspective of the renal involvement in MIS-C, the incidence of AKI, the pathophysiology of AKI in MIS-C and the proposed therapeutic regimens available, including the need for kidney replacement therapy for a child with AKI associated with MIS-C. As the disease is rapidly evolving, more detailed clinical prospective studies are required to understand MIS-C and its role in AKI better.
| S-EPMC8083308 | biostudies-literature
Project description:BackgroundAlthough the radiographic features of coronavirus disease 2019 (COVID-19) in children have been described, the distinguishing features of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 are not well characterized.ObjectiveWe compared the chest radiographic findings of MIS-C with those of COVID-19 and described other distinguishing imaging features of MIS-C.Materials and methodsWe performed a retrospective case series review of children ages 0 to 18 years who were hospitalized at Children's Healthcare of Atlanta from March to May 2020 and who either met the Centers for Disease Control and Prevention (CDC) case definition for MIS-C (n=11) or who had symptomatic, laboratory-confirmed COVID-19 (n=16). Two radiologists reviewed the most severe chest radiographs for each patient. The type and distribution of pulmonary opacities and presence or absence of pleural effusions were recorded. The chest radiographs were categorized based on potential COVID-19 imaging findings as typical, indeterminate, atypical or negative. An imaging severity score was also assigned using a simplified version of the Radiographic Assessment of Lung Edema Score. Findings were statistically compared between patients with MIS-C and those with COVID-19. Additional imaging findings of MIS-C were also described.ResultsRadiographic features of MIS-C included pleural effusions (82% [9/11]), pulmonary consolidations (73% [8/11]) and ground glass opacities (91% [10/11]). All of the lung opacities (100% [10/10]) were bilateral, and the majority of the pleural effusions (67% [6/9]) were bilateral. Compared to children with COVID-19, children with MIS-C were significantly more likely to develop pleural effusions on chest radiograph (82% [9/11] vs. 0% [0/0], P-value <0.01) and a lower zone predominance of pulmonary opacifications (100% [10/10] vs. 38% [5/13], P-value <0.01). Children with MIS-C who also had abdominal imaging had intra-abdominal inflammatory changes.ConclusionKey chest radiographic features of MIS-C versus those of COVID-19 were pleural effusions and lower zone pulmonary opacifications as well as intra-abdominal inflammation. Elucidating the distinguishing radiographic features of MIS-C may help refine the case definition and expedite diagnosis and treatment.
| S-EPMC7785920 | biostudies-literature
Project description:Background and objectivesHigh-quality epidemiologic data on AKI in children are particularly lacking in developing countries. This study aimed to assess the epidemiology and clinical correlates of AKI among hospitalized children in China.Design, setting, participants, & measurementsWe performed a multicenter study, in a cohort of hospitalized children aged 1 month to 18 years, from 25 general and children's hospitals in China during 2013-2015. We obtained patient-level data from the electronic hospitalization information system and laboratory databases of all children who had at least two serum creatinine tests within any 7-day window during their first 30 days of hospitalization. We identified AKI events according to the creatinine criteria of Kidney Disease Improving Global Outcomes. The in-hospital outcomes of AKI, including mortality, kidney recovery, and length of stay, were assessed. We estimated the corresponding hazard ratios using a Cox proportional hazard model, with adjustment for age, sex, comorbidities, and clinical procedures.ResultsA total of 19,908 (20%) patients with AKI were identified among 101,836 pediatric inpatients, of which 7220 (7%) were community acquired and 12,688 (13%) were hospital acquired. Up to 96% of these AKI events were not diagnosed on the discharge records. The cumulative incidence of AKI in infants (28%) was twice that in adolescents (12%). The profiles of risk factors differed between community-acquired and hospital-acquired AKI and varied with age. Diarrhea and sepsis were the top risk factors for community-acquired AKI, each contributing 6% of the risk. Congenital heart disease/cardiac surgery was the major risk factor for hospital-acquired AKI, contributing to 19% of cases. Exposure to nephrotoxic drugs, mostly nonsteroidal anti-inflammatory drugs and proton pump inhibitors, was common in hospitalized children and was associated with a higher risk of AKI. Death occurred in 842 out of 19,908 patients (4%) with AKI versus 450 out of 81,478 children (0.5%) without AKI. The risk of in-hospital death was higher among children with severe AKI, shock, and respiratory failure. Pediatric AKI was associated with longer hospital stay and higher daily cost, even after adjustment for covariates.ConclusionsPediatric AKI is common and is substantially underdiagnosed in China.
| S-EPMC6302328 | biostudies-literature
Project description:A multisystem inflammatory syndrome in children (MIS-C) was identified as an entity temporally associated with the present COVID-19 pandemic. This inflammatory syndrome affects various organ systems including the gastrointestinal and hepatobiliary systems. The following study was undertaken to primarily detect the fraction of children who had pancreatitis as major organ involvement during the development of MIS-C. The secondary objective was to evaluate their clinical and investigational profile as well as the outcome of management.MethodsA retrospective chart analysis of all children admitted in a tertiary pediatric center from April to December 2020, diagnosed as COVID-19 associated MIS-C, was done. Those presenting with acute pancreatitis were detected and detailed clinical features, investigations, treatments, as well as outcomes, were recorded.ResultsA total of 17 children were diagnosed as MIS-C associated with SARS-CoV-2 in the above-mentioned period. Among them, 9 (53%) children had pancreatitis right from the start of the illness; 5 (56%) children with pancreatitis presented with shock. A very high CRP and cardiac involvement were observed in all. A severe reduction of myocardial contractility was associated with poor outcomes. Necrotic pancreatitis was not noted in any of them. A mortality of 22% was documented in this group and a 3-month outcome among those who survived displayed complete resolution of all cardiac as well as pancreatic abnormalities.ConclusionAcute pancreatitis can be an essential cause of abdominal symptoms in COVID-19-related MIS-C. Pancreatitis may be considered to be one of the parameters in the diagnostic criteria of MIS-C.
| S-EPMC8667678 | biostudies-literature
Project description:As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development. TRANSLATIONS: For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section.
| S-EPMC7431129 | biostudies-literature
Project description:ObjectiveThe objective of this study is to evaluate pediatric patients using existing macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) scoring systems to determine how these systems identify patients with cytokine storm syndrome (CSS) in the setting of a multisystem inflammatory syndrome in children (MIS-C) and active coronavirus disease 2019 (COVID-19) infection.MethodsHospitalized pediatric patients with MIS-C and active COVID-19 infection at a single institution were identified. Infectious data, clinical findings, and laboratory values were collected, and patients were stratified by disease severity. Eight historically used scoring systems for MAS, HLH, and CSS were examined in the cohort of patients with MIS-C and pediatric COVID-19.ResultsThe HLH-2004 criteria and HScore did not identify any patients as having CSS on admission, with only one patient with COVID-19 meeting criteria at peak disease severity. The 2016 systemic juvenile idiopathic arthritis (sJIA)/MAS criteria, ferritin/erythrocyte sedimentation rate (ESR) ratio, and COVID-19 CSS Quick Score most frequently identified CSS in this population and distinguished between COVID-19 and MIS-C hyperinflammation. The 2019 MAS/sJIA (MS) score and the COVID-19-associated hyperinflammatory syndrome (cHIS) criteria were less likely to identify CSS, as the MS score overestimated CSS and the cHIS resulted in similar scores regardless of severity or disease type. The Caricchio COVID-Cytokine Storm (COVID-CS) criteria identified patients with COVID-19 frequently but was less useful in MIS-C because of its COVID-19-specific criteria.ConclusionMIS-C and pediatric COVID-19 result in relatively unique CSSs and patterns of inflammation. Existing scoring systems for CSSs likely do not capture the full breadth of this disease process in MIS-C and pediatric COVID-19.
| S-EPMC8652831 | biostudies-literature