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1.
Pediatr Emerg Care ; 38(2): 83-91, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1662152

ABSTRACT

ABSTRACT: Multisystem inflammatory syndrome in children (MIS-C) is a syndrome of abnormal immune response after severe acute respiratory syndrome coronavirus 2 infection that can result in organ dysfunction including severe cardiovascular compromise in children. Increased evidence supports a clinical and laboratory profile in MIS-C distinct from Kawasaki disease, with MIS-C typically occurring in older children and with more prominent gastrointestinal and neurologic symptoms, as well as increased inflammation, lymphopenia, and cardiac injury on laboratory testing. However, high-level evidence regarding best practices for treatment and long-term outcomes in MIS-C is limited.


Subject(s)
COVID-19 , Connective Tissue Diseases , COVID-19/complications , Child , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
2.
Infect Control Hosp Epidemiol ; : 1-9, 2021 Dec 02.
Article in English | MEDLINE | ID: covidwho-1569174

ABSTRACT

OBJECTIVE: To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study open to adult employees at the Children's Hospital of Philadelphia, conducted April 20-December 17, 2020. METHODS: Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity. RESULTS: In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03-3.68), Black race (HR, 2.70; 95% CI, 1.24-5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71-6.88) were associated with statistically significant increased risk for seropositivity. CONCLUSIONS: Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.

4.
Blood ; 136(Supplement 1):28-29, 2020.
Article in English | PMC | ID: covidwho-1338970

ABSTRACT

Introduction: During the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), 3 distinct phenotypes have emerged in children. The majority of children have mild or no symptoms. Similar to adults, a minority of children can be severely affected with respiratory distress requiring intensive care. Finally, they may develop a phenomenon presumed unique to children termed Multisystem Inflammatory Syndrome in Children (MIS-C). MIS-C is a hyperinflammatory syndrome characterized by fever and organ dysfunction (particularly cardiac) in the setting of recent COVID-19 infection. Reports from the adult literature have invoked thrombotic microangiopathy (TMA) and complement activation as a potential cause for severe manifestations of COVID-19 (Zhang et al. NEJM. 2020;Campbell et al. Circulation 2020). Soluble C5b9 (sC5b-9), the terminal complement complex, has been implicated as a marker of hematopoietic stem cell transplant associated TMA (HSCT-TMA;Jodele et al. Blood 2014). We sought to elucidate the role of terminal complement activation and TMA in the different pediatric disease phenotypes.Methods: We enrolled children admitted to the Children's Hospital of Philadelphia during the COVID-19 pandemic who had evidence of SARS-CoV-2 infection on reverse transcriptase polymerase chain reaction (RT-PCR) from mucosa, or met clinical criteria for MIS-C. Patients (pts) were classified in to 3 categories: minimal COVID-19 symptoms or incidental finding of SARS-CoV-2 infection, severe COVID-19 requiring ventilatory support, or MIS-C. To investigate the role of TMA in children with COVID-19 we measured sC5b-9 in plasma of pts with the 3 manifestations of SARS-CoV-2, and in healthy controls. sC5b9 was measured in triplicate at two dilutions by ELISA. Proinflammatory cytokines were measured using V-Plex Pro-inflammatory Panel 1 Human Kits and analyzed on a QuickPlex SQ120. P-values were computed using Dunn's multiple comparisons test after Kruskal-Wallis testing. Blood smears were examined by a hematologist and hematopathologist for schistocytes.Results: 50 pts were enrolled on whom complete sC5b9 data were available: minimal COVID-19 (N=18), severe COVID-19 (N=11), and MIS-C (N=21). Plasma was obtained on healthy controls (N=26). The median sC5b9 level in healthy controls (57 ng/mL) differed significantly (p<0.001 in each case;Figure 1A) from that in pts with minimal disease (392 ng/mL), severe disease (646 ng/mL), and MIS-C (630 ng/mL);differences between MIS-C, minimal, and severe were not statistically significant. Elevations in sC5b9 correlated in a statistically significant manner with the maximum creatinine and blood urea nitrogen (BUN) measured during hospitalization (Figure 1B&C), but not age (p=0.512). sC5b9 did not correlate with lactate dehydrogenase (LDH), nor with the lowest levels of fibrinogen, hemoglobin or platelet counts. Of pts with available data, 19/26 (73.1%) had elevated LDH, 2/31 (6.4%) had hypofibrinogenemia, 35/47 (74.5%) were anemic, and 28/47 (59.6%) were thrombocytopenic.Pro-inflammatory cytokines were measured. Of particular interest to TMA is the neutrophil chemotactic factor IL-8, because of its role as a marker of endothelial damage (Dvorak et al. Front Pediatr 2019). Levels of IL-8 differed significantly between pts with MIS-C (p=0.0166) or pts with severe COVID-19 (p=0.0079), when compared to minimal COVID-19 pts;but not between pts with MIS-C and severe disease (p = 0.99).Blood smears were available on 34 patients. Schistocytes were present in 13/15 (87%) patients with MIS-C, 7/8 (87%) patients with severe COVID-19 and 5/11 (45%) patients with minimal COVID-19 (χ2=6.59, p=0.037).Conclusions: We demonstrate derangements of the final common pathway of complement activation in children with the 3 presentations of SARS-CoV-2. Strikingly, sC5b9s were abnormal even in children with minimal disease or incidental infection. Renal dysfunction correlated with elevations in sC5b9, strengthening the evidence that TMA plays a role in the pa hophysiology of SARS-CoV-2 infection. Future work is aimed at further characterizing the role of the complement cascade in the pathogenesis of MIS-C and COVID-19 in children. The long-term complications of endothelial damage and complement activation are unknown and extended follow-up is warranted.Figure 1

6.
Pediatr Emerg Care ; 36(11): 554-558, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-990957

ABSTRACT

OBJECTIVE: The aim of the study was to compare presenting clinical and laboratory features among children meeting the surveillance definition for multisystem inflammatory syndrome in children (MIS-C) across a range of illness severities. METHODS: This is a retrospective single-center study of patients younger than 21 years presenting between March 1 and May 15, 2020. Included patients met the Centers for Disease Control and Prevention criteria for MIS-C (inflammation, fever, involvement of 2 organ systems, lack of alternative diagnoses). We defined 3 subgroups by clinical outcomes: (1) critical illness requiring intensive care interventions; (2) patients meeting Kawasaki disease (KD) criteria but not requiring critical care; and (3) mild illness not meeting either criteria. A comparator cohort included patients with KD at our institution during the same time frame in 2019. RESULTS: Thirty-three patients were included (5, critical; 8, 2020 KD; 20, mild). The median age for the critical group was 10.9 years (2.7 for 2020 KD; 6.0 for mild, P = 0.033). The critical group had lower median absolute lymphocyte count (850 vs 3005 vs 2940/uL, P = 0.005), platelets (150 vs 361 vs 252 k/uL, P = 0.005), and sodium (129 vs 136 vs 136 mmol/L, P = 0.002), and higher creatinine (0.7 vs 0.2 vs 0.3 mg/dL, P = 0.002). In the critical group, 60% required vasoactive medications, and 40% required mechanical ventilation. Clinical and laboratories features were similar between the 2020 and 2019 KD groups. CONCLUSIONS: We describe 3 groups with inflammatory syndromes during the SARS-CoV-2 pandemic. The initial profile of lymphopenia, thrombocytopenia, hyponatremia, and abnormal creatinine may help distinguish critically ill MIS-C patients from classic/atypical KD or more benign acute inflammation.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Critical Care/methods , Disease Management , Mucocutaneous Lymph Node Syndrome/diagnosis , Pandemics , Pneumonia, Viral/diagnosis , Adolescent , COVID-19 , Child , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Diagnosis, Differential , Female , Humans , Male , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Retrospective Studies , SARS-CoV-2
7.
J Pediatr ; 226: 274-277.e1, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-741374

ABSTRACT

We conducted a descriptive time-series study of pediatric emergency healthcare use during the onset of severe acute respiratory syndrome coronavirus 2 pandemic after a state-wide stay-at-home order. Our study demonstrated decreased volume, increased acuity, and generally consistent chief complaints compared with the prior 3 years (2017 through 2019). Ingestions became a significantly more common chief complaint in 2020.


Subject(s)
COVID-19/prevention & control , Emergency Service, Hospital/trends , Facilities and Services Utilization/trends , Hospitals, Pediatric/trends , Patient Acceptance of Health Care/statistics & numerical data , Physical Distancing , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Hospitals, Urban/trends , Humans , Infant , Infant, Newborn , Interrupted Time Series Analysis , Male , Protective Factors , Risk Factors , Severity of Illness Index , Tertiary Care Centers/trends , Trauma Severity Indices , Wounds and Injuries/diagnosis , Wounds and Injuries/epidemiology , Wounds and Injuries/etiology , Wounds and Injuries/therapy , Young Adult
8.
J Clin Invest ; 130(11): 5967-5975, 2020 11 02.
Article in English | MEDLINE | ID: covidwho-690425

ABSTRACT

BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.


Subject(s)
Betacoronavirus/metabolism , Complement Membrane Attack Complex/metabolism , Coronavirus Infections , Cytokines/blood , Pandemics , Pneumonia, Viral , Systemic Inflammatory Response Syndrome , Adolescent , COVID-19 , Child , Child, Preschool , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Female , Humans , Male , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/epidemiology
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