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1.
BMJ Case Rep ; 15(5)2022 May 10.
Article in English | MEDLINE | ID: covidwho-1832381

ABSTRACT

Multisystem inflammatory syndrome in adults (MIS-A) has been reported as a rare but severe consequence of COVID-19 infection. Adult patients were more likely to present with hypotension and cardiac illness when compared with multisystem inflammatory syndrome in children. Although the exact prevalence of MIS-A is unknown, more cases have been observed in men and younger adults. The pathophysiology of MIS-A is also unclear, but is thought to be caused by a delayed, dysregulated immune response. Given no established guideline for treatment of MIS-A, treatment has been based on case reports. We present a case of MIS-A in a woman in her 60s who had severe hypotension, progressive dyspnoea, massive pleural effusion, hypoxaemia, thyroiditis and multiple organ failure, which dramatically improved after treatment with corticosteroid and interleukin 6 inhibitor.


Subject(s)
COVID-19 , Hypotension , Thyroiditis , Adrenal Cortex Hormones/therapeutic use , Adult , COVID-19/complications , COVID-19/drug therapy , Child , Female , Humans , Hypoxia/drug therapy , Hypoxia/etiology , Interleukin-6 , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy
2.
Pediatrics ; 149(5)2022 05 01.
Article in English | MEDLINE | ID: covidwho-1779805

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a severe inflammatory response described in children after infection with severe acute respiratory syndrome coronavirus 2. We present a case of a 9-year-old African American boy with 2 distinct illnesses that were both consistent with MIS-C. He first presented in the early stages of our understanding of MIS-C with predominantly neurologic and gastrointestinal symptoms and demonstrated elevated inflammatory markers consistent with MIS-C. He was treated with intravenous immunoglobulin with complete resolution of signs and symptoms. After 7 months of good health, he returned with a second, distinct illness characterized by fever, rash, gastrointestinal symptoms, and elevated inflammatory markers that met the criteria for MIS-C. In addition, we identified new dilatation of the left anterior descending coronary artery. He improved rapidly after treatment with intravenous immunoglobulin, aspirin, and steroids. Our report highlights the need to achieve a better understanding of this entity's pathogenesis and clinical course and to improve anticipatory guidance for children with MIS-C.


Subject(s)
COVID-19 , COVID-19/complications , Child , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy
3.
Pediatr Infect Dis J ; 41(3): e93-e94, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1684870

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection is well known. We describe a 12-year-old child developing MIS-C after receiving 2 doses of mRNA COVID-19 vaccines without clinical evidence of COVID-19 infection. A possible association between the SARS-CoV-2 vaccine and MIS-C cannot be excluded.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/complications , Systemic Inflammatory Response Syndrome/etiology , /adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/etiology , COVID-19/prevention & control , Child , Diagnosis, Differential , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy
5.
J Infect Chemother ; 28(6): 814-818, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1649662

ABSTRACT

Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab. A Japanese boy who was diagnosed with coronavirus disease 2019 (COVID-19) before a month developed MIS-C with fulfilling six principal symptoms of KD. Laboratory data showed extreme hyperferritinemia (11,404 ng/mL), besides lymphopenia and thrombocytopenia. The patient was refractory to initial therapy with intravenous immunoglobulin (IVIG; 2 g/kg), aspirin, and prednisolone. He was therefore administered a second IVIG (2 g/kg) and infliximab (5 mg/kg) on days 7 and 8 from the onset of fever, respectively, which resulted in an improvement of clinical symptoms. Only four Japanese cases with MIS-C were reported and all of them were responsive to IVIG. The hyperferritinemia in this case was distinctive from previously reported MIS-C cases in Japan and other cohorts and may be associated with refractoriness to IVIG therapy. Marked elevation of circulating ferritin levels is known to be induced by tumor necrosis factor-α, which plays a key role in the pathogenesis of both KD and MIS-C. Thus, for MIS-C patients with hyperferritinemia, early intervention with adjunctive infliximab may induce a more rapid resolution of inflammation and improve outcome. Because MIS-C may be heterogeneous with respect to immunopathology, genetic background, clinical phenotypes and response to therapies, optimized treatment strategies according to immunopathogenesis are required.


Subject(s)
COVID-19 , Connective Tissue Diseases , Hyperferritinemia , Mucocutaneous Lymph Node Syndrome , COVID-19/complications , COVID-19/drug therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Infliximab/therapeutic use , Japan , Male , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy
6.
MMWR Morb Mortal Wkly Rep ; 71(2): 52-58, 2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1622893

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a severe postinfectious hyperinflammatory condition, which generally occurs 2-6 weeks after a typically mild or asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19 (1-3). In the United States, the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine is currently authorized for use in children and adolescents aged 5-15 years under an Emergency Use Authorization and is fully licensed by the Food and Drug Administration for persons aged ≥16 years (4). Prelicensure randomized trials in persons aged ≥5 years documented high vaccine efficacy and immunogenicity (5),§ and real-world studies in persons aged 12-18 years demonstrated high vaccine effectiveness (VE) against severe COVID-19 (6). Recent evidence suggests that COVID-19 vaccination is associated with lower MIS-C incidence among adolescents (7); however, VE of the 2-dose Pfizer-BioNTech regimen against MIS-C has not been evaluated. The effectiveness of 2 doses of Pfizer-BioNTech vaccine received ≥28 days before hospital admission in preventing MIS-C was assessed using a test-negative case-control design¶ among hospitalized patients aged 12-18 years at 24 pediatric hospitals in 20 states** during July 1-December 9, 2021, the period when most MIS-C patients could be temporally linked to SARS-CoV-2 B.1.617.2 (Delta) variant predominance. Patients with MIS-C (case-patients) and two groups of hospitalized controls matched to case-patients were evaluated: test-negative controls had at least one COVID-19-like symptom and negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) or antigen-based assay results, and syndrome-negative controls were hospitalized patients without COVID-19-like illness. Among 102 MIS-C case-patients and 181 hospitalized controls, estimated effectiveness of 2 doses of Pfizer-BioNTech vaccine against MIS-C was 91% (95% CI = 78%-97%). All 38 MIS-C patients requiring life support were unvaccinated. Receipt of 2 doses of the Pfizer-BioNTech vaccine is associated with a high level of protection against MIS-C in persons aged 12-18 years, highlighting the importance of vaccination among all eligible children.


Subject(s)
/therapeutic use , COVID-19/complications , Systemic Inflammatory Response Syndrome/drug therapy , Adolescent , COVID-19/drug therapy , Case-Control Studies , Child , Female , Hospitalization/statistics & numerical data , Humans , Male , Patient Acuity , SARS-CoV-2/immunology , United States/epidemiology
7.
Virol J ; 19(1): 9, 2022 01 06.
Article in English | MEDLINE | ID: covidwho-1613240

ABSTRACT

BACKGROUND: Multisystem inflammatory syndrome (MIS), which develops after a past covid-19 infection. MIS can be described in different tissue inflammation, including the heart, lung, kidney, brain, skin, eye, and or gastrointestinal organs at the presence of COVID-19. Initially, MIS was described in Europe in children infected with SARS-CoV-2, then it was recently seen in the USA in 2020. MIS is a rare but serious disease condition associated with COVID-19 that can affect children (MIS-C) and adults (MIS-A). CASE PRESENTATION: A 44-year-old male who showed MIS-A in 59-day after his first covid-19 contact history. The patient presented to our emergency department with complaints of high fever, nausea, weakness, redness of the eyes, headache, and joint pain. On the second day of his hospitalization, a maculopapular skin lesion was seen in most of the skin. His fever could not be controlled even given paracetamol and broad effective antibiotics. His clinical, radiological, and laboratory findings showed that he had MIS-A. The patient was given intravenous pulse methylprednisolone and intravenous immunoglobulin (IVIG). These treatments, then, resulted in improvement of his clinical conditions, including fever and skin lesions, on the second day of the treatment. The patient was discharged in 14 days after the treatment. CONCLUSION: This report indicated that diagnosis and treatment of MIS-A could result in reducing patient morbidity and mortality.


Subject(s)
COVID-19/complications , Glucocorticoids/therapeutic use , Methylprednisolone/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Adult , COVID-19/diagnosis , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Humans , Immunoglobulins, Intravenous , Injections, Intraventricular , Male , Methylprednisolone/administration & dosage , SARS-CoV-2 , Skin Diseases , Systemic Inflammatory Response Syndrome/diagnosis
8.
Pediatr Infect Dis J ; 41(3): e87-e89, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1608728

ABSTRACT

The pathophysiology of multisystem inflammatory syndrome (MIS) in children (MIS-C) is unknown. It occurs several weeks after COVID-19 infection or exposure; however, MIS is rarely reported after COVID-19 vaccination, and cases are mostly in adults. Herein, we present a 12-year-old male who had no prior COVID-19 infection or exposure and developed MIS-C after his first dose of COVID-19 mRNA vaccine.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/complications , Systemic Inflammatory Response Syndrome/etiology , Vaccines, Synthetic/adverse effects , /adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/etiology , COVID-19/prevention & control , Child , Diagnosis, Differential , Drug Therapy, Combination , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Methylprednisolone/therapeutic use , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy
9.
Pediatr Infect Dis J ; 41(3): e104-e105, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1592757

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a serious complication that is observed most commonly in pediatric patients following severe acute respiratory syndrome coronavirus 2 infections. However, the mechanism and predictors of disease are poorly understood. There are no prior reports of MIS-C among patients who have been fully vaccinated, and only a single case of MIS in an adult patient who had received his second shot just 4 days prior to symptom onset. Here, we present an adolescent with sickle cell disease who was fully vaccinated against severe acute respiratory syndrome coronavirus 2 and had no prior history of known or suspected infection, who presented in shock and was ultimately diagnosed with MIS-C. This case highlights the importance of clinical suspicion for MIS-C even when patients are fully vaccinated.


Subject(s)
Anemia, Sickle Cell/complications , COVID-19 Vaccines/adverse effects , COVID-19/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/etiology , Vaccines, Synthetic/adverse effects , /adverse effects , Adolescent , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/etiology , COVID-19/prevention & control , Diagnosis, Differential , Drug Therapy, Combination , Female , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Methylprednisolone/therapeutic use , Pandemics , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy
10.
N Engl J Med ; 385(1): 11-22, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1585668

ABSTRACT

BACKGROUND: Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS: We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS: Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS: We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).


Subject(s)
COVID-19/drug therapy , Glucocorticoids/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Adolescent , Antibodies, Viral , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Child , Child, Preschool , Cohort Studies , Confidence Intervals , Drug Therapy, Combination , Female , Hospitalization , Humans , Immunomodulation , Male , Propensity Score , Regression Analysis , Respiration, Artificial , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/mortality , Systemic Inflammatory Response Syndrome/therapy , Treatment Outcome
11.
BMC Cardiovasc Disord ; 21(1): 522, 2021 10 29.
Article in English | MEDLINE | ID: covidwho-1486551

ABSTRACT

BACKGROUND: With the high prevalence of COVID-19 infections worldwide, the multisystem inflammatory syndrome in adults (MIS-A) is becoming an increasingly recognized entity. This syndrome presents in patients several weeks after infection with COVID-19 and is associated with thrombosis, elevated inflammatory markers, hemodynamic compromise and cardiac dysfunction. Treatment is often with steroids and intravenous immunoglobulin (IVIg). The pathologic basis of myocardial injury in MIS-A, however, is not well characterized. In our case report, we obtained endomyocardial biopsy that revealed a pattern of myocardial injury similar to that found in COVID-19 cardiac specimens. CASE PRESENTATION: A 26-year-old male presented with fevers, chills, headache, nausea, vomiting, and diarrhea 5 weeks after his COVID-19 infection. His SARS-CoV-2 PCR was negative and IgG was positive, consistent with prior infection. He was found to be in cardiogenic shock with biventricular failure, requiring inotropes and diuretics. Given concern for acute fulminant myocarditis, an endomyocardial biopsy (EMB) was performed, showing an inflammatory infiltrate consisting predominantly of interstitial macrophages with scant T lymphocytes. The histologic pattern was similar to that of cardiac specimens from COVID-19 patients, helping rule out myocarditis as the prevailing diagnosis. His case was complicated by persistent hypoxemia, and a computed tomography scan revealed pulmonary emboli. He received IVIg, steroids, and anticoagulation with rapid recovery of biventricular function. CONCLUSIONS: MIS-A should be considered as the diagnosis in patients presenting several weeks after COVID-19 infection with severe inflammation and multi-organ involvement. In our case, EMB facilitated identification of MIS-A and guided therapy. The patient's biventricular function recovered with IVIg and steroids.


Subject(s)
Anticoagulants/administration & dosage , COVID-19 , Myocarditis/diagnosis , Shock, Cardiogenic , Systemic Inflammatory Response Syndrome , Adult , Biopsy/methods , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/immunology , COVID-19/physiopathology , Cardiotonic Agents/administration & dosage , Diagnosis, Differential , Diuretics/administration & dosage , Electrocardiography/methods , Humans , Immunoglobulins, Intravenous/administration & dosage , Male , Myocardium/pathology , Radiography, Thoracic/methods , SARS-CoV-2 , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/drug therapy , Shock, Cardiogenic/etiology , Shock, Cardiogenic/physiopathology , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/physiopathology , Treatment Outcome
12.
Viruses ; 13(11)2021 10 22.
Article in English | MEDLINE | ID: covidwho-1481020

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, threatens the entire world. It has affected every aspect of life and increased the burden on both healthcare and socioeconomic systems. Current studies have revealed that excessive inflammatory immune responses are responsible for the severity of COVID-19, which suggests that anti-inflammatory drugs may be promising therapeutic treatments. However, there are currently a limited number of approved therapeutics for COVID-19. Toll-like receptors (TLRs), which recognize microbial components derived from invading pathogens, are involved in both the initiation of innate responses against SARS-CoV-2 infection and the hyperinflammatory phenotype of COVID-19. In this review, we provide current knowledge on the pivotal role of TLRs in immune responses against SARS-CoV-2 infection and demonstrate the potential effectiveness of TLR-targeting drugs on the control of hyperinflammation in patients with COVID-19.


Subject(s)
COVID-19/immunology , Immunity, Innate , SARS-CoV-2/immunology , Toll-Like Receptors/immunology , Animals , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , COVID-19/virology , Cytokine Release Syndrome , Humans , SARS-CoV-2/physiology , Severity of Illness Index , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/drug therapy , Toll-Like Receptors/antagonists & inhibitors , Toll-Like Receptors/metabolism
13.
Rheumatol Int ; 42(3): 477-484, 2022 03.
Article in English | MEDLINE | ID: covidwho-1473997

ABSTRACT

To study the clinical, laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to coronavirus disease 2019 (COVID-19) in a resource-limited setting. All children meeting the World Health Organization case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4-6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the stata-12 software. Thirty-one children with MIS-C were enrolled in an 11-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight percent of children presented with shock, and 22.5% required mechanical ventilation. HSP like rash, gangrene and arthritis were uncommon clinical observations.The median duration of hospital stay was 9 (6.5-18.5) days: four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) [median (IQR)] were significantly higher in non-survivors as compared to survivors [1061 (581, 2750) vs 309.5 (140, 720.08), p value = 0.045]. Six patients had coronary artery involvement; five recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome. Most children with MIS-C present with acute hemodynamic and respiratory symptoms.The outcome is favorable in children without preexisting comorbidities.Raised ferritin level may be a poor prognostic marker. The coronary outcomes at follow-up were reassuring.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/complications , Immunoglobulins, Intravenous/therapeutic use , Systemic Inflammatory Response Syndrome/etiology , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Longitudinal Studies , Male , Systemic Inflammatory Response Syndrome/drug therapy , Treatment Outcome
15.
Crit Care Med ; 49(11): e1151-e1156, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1467423

ABSTRACT

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.


Subject(s)
COVID-19/complications , Shock/pathology , Systemic Inflammatory Response Syndrome/pathology , Adrenal Cortex Hormones/therapeutic use , Angiopoietin-2/blood , Biomarkers , C-Reactive Protein/analysis , COVID-19/drug therapy , COVID-19/pathology , Cardiotonic Agents/therapeutic use , Child , Female , Humans , Immunoglobulins/therapeutic use , Intensive Care Units, Pediatric , Interleukin-6/blood , Lactic Acid/blood , Male , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Shock, Cardiogenic/pathology , Systemic Inflammatory Response Syndrome/drug therapy , Troponin/blood , Vasoconstrictor Agents/therapeutic use , Ventricular Function, Left
16.
Pediatrics ; 148(4)2021 10.
Article in English | MEDLINE | ID: covidwho-1465438

ABSTRACT

BACKGROUND AND OBJECTIVES: Myocardial dysfunction and coronary abnormalities are prominent features of multisystem inflammatory syndrome in children (MIS-C). In this study we aim to evaluate the early and midterm outcomes of MIS-C. METHODS: This is a longitudinal 6-month cohort study of all children admitted and treated for MIS-C from April 17 to June 20, 2020. Patients were followed ∼2 weeks, 8 weeks, and 6 months postadmission, with those with coronary aneurysms evaluated more frequently. RESULTS: Acutely, 31 (62%) patients required intensive care with vasoactive support, 26 (52%) had left ventricular (LV) systolic dysfunction, 16 (32%) had LV diastolic dysfunction, 8 (16%) had coronary aneurysms (z score ≥2.5), and 4 (8%) had coronary dilation (z score <2.5). A total of 48 patients (96%) received immunomodulatory treatment. At 2 weeks, there was persistent mild LV systolic dysfunction in 1 patient, coronary aneurysms in 2, and dilated coronary artery in 1. By 8 weeks through 6 months, all patients returned to functional baseline with normal LV systolic function and resolution of coronary abnormalities. Cardiac MRI performed during recovery in select patients revealed no myocardial edema or fibrosis. Some patients demonstrated persistent diastolic dysfunction at 2 weeks (5, 11%), 8 weeks (4, 9%), and 6 months (1, 4%). CONCLUSIONS: Children with MIS-C treated with immunomodulators have favorable early outcomes with no mortality, normalization of LV systolic function, recovery of coronary abnormalities, and no inflammation or scarring on cardiac MRI. Persistence of diastolic dysfunction is of uncertain significance and indicates need for larger studies to improve understanding of MIS-C. These findings may help guide clinical management, outpatient monitoring, and considerations for sports clearance.


Subject(s)
COVID-19/complications , Coronary Aneurysm/etiology , Systemic Inflammatory Response Syndrome/complications , Ventricular Dysfunction, Left/etiology , Adolescent , COVID-19/drug therapy , Child , Child, Preschool , Coronary Vessels/pathology , Female , Heart/diagnostic imaging , Humans , Infant , Longitudinal Studies , Magnetic Resonance Imaging , Male , Myocarditis/drug therapy , Myocarditis/etiology , Systemic Inflammatory Response Syndrome/drug therapy , Ventricular Function, Left/drug effects
17.
Postgrad Med ; 133(8): 994-1000, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1450321

ABSTRACT

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition resulting in excessive response of the immune system after SARS-CoV-2 infection. We report a single-center cohort of children with MIS-C, describing the spectrum of presentation, therapies, clinical course, and short-term outcomes. METHODS: This is a prospective observational study from to a tertiary pediatric rheumatology center including patients (aged 1 month to 21 years) diagnosed with MIS-C between April 2020-April 2021. Demographic, clinical, laboratory results and follow-up data were collected through the electronic patient record system and analyzed. RESULTS: A total of 67 patients with MIS-C were included in the study. Fever was detected in all patients; gastrointestinal system symptoms were found in 67.2% of the patients, rash in 38.8%, conjunctivitis in 31.3%, hypotension in 26.9% myocarditis, and/or pericarditis in 22.4%, respectively. Respiratory symptoms were only in five patients (7.5%). Kawasaki Disease like presentation was found 37.3% of the patients. The mean duration of hospitalization was 11.8 7.07 days. Fifty-seven patients (85%) received intravenous immunoglobulin (IVIG), 45 (67%) received corticosteroids, 17 (25.3%) received anakinra, and one (1.5%) received tocilizumab. Seven of the patients (10.4%) underwent therapeutic plasma exchange (TPE). In 21 (31.3%) patients, a pediatric intensive care unit (PICU) was required in a median of 2 days. The first finding to improve was fever, while the first parameter to decrease was ferritin (median 6.5 days (IQR, 4-11.2 days)). Sixty-five patients were discharged home with a median duration of hospital stay of 10 days (IQR, 7-15 days). CONCLUSION: Patients with MIS-C may have severe cardiac findings and intensive care requirements in admission and hospital follow-up. The vast majority of these findings improve with effective treatment without any sequelae until discharge and in a short time in follow-up. Although the pathogenesis and treatment plan of the disease are partially elucidated, follow-up studies are needed in terms of long-term prognosis and relapse probabilities.


Subject(s)
COVID-19/complications , Intensive Care Units, Pediatric/statistics & numerical data , Rheumatology/statistics & numerical data , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/physiopathology , Administration, Intravesical , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunoglobulins/administration & dosage , Immunoglobulins/therapeutic use , Infant , Infant, Newborn , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Male , Oxytocin/administration & dosage , Oxytocin/analogs & derivatives , Oxytocin/therapeutic use , Plasma Exchange , Prospective Studies
18.
Sci Rep ; 11(1): 19458, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1447326

ABSTRACT

Efficacious therapeutics for Ebola virus disease are in great demand. Ebola virus infections mediated by mucosal exposure, and aerosolization in particular, present a novel challenge due to nontypical massive early infection of respiratory lymphoid tissues. We performed a randomized and blinded study to compare outcomes from vehicle-treated and remdesivir-treated rhesus monkeys in a lethal model of infection resulting from aerosolized Ebola virus exposure. Remdesivir treatment initiated 4 days after exposure was associated with a significant survival benefit, significant reduction in serum viral titer, and improvements in clinical pathology biomarker levels and lung histology compared to vehicle treatment. These observations indicate that remdesivir may have value in countering aerosol-induced Ebola virus disease.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Ebolavirus/drug effects , Hemorrhagic Fever, Ebola/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/pharmacology , Administration, Intravenous , Aerosols , Alanine/administration & dosage , Alanine/pharmacology , Animals , Antiviral Agents/administration & dosage , Disease Models, Animal , Female , Hemorrhagic Fever, Ebola/blood , Kaplan-Meier Estimate , Liver/drug effects , Liver/virology , Lung/pathology , Lung/virology , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymph Nodes/virology , Macaca mulatta , Male , Random Allocation , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/virology , Viral Load/drug effects , Viremia/drug therapy
19.
Acta Pharmacol Sin ; 42(11): 1913-1920, 2021 11.
Article in English | MEDLINE | ID: covidwho-1437673

ABSTRACT

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.


Subject(s)
COVID-19 , Colitis, Ulcerative , Disulfiram/pharmacokinetics , Lactoferrin , Systemic Inflammatory Response Syndrome , Acetaldehyde Dehydrogenase Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Biomimetic Materials/pharmacology , COVID-19/drug therapy , COVID-19/immunology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Disease Models, Animal , Disulfiram/pharmacology , Drug Carriers/pharmacology , Humans , Immunosuppressive Agents/pharmacology , Lactoferrin/metabolism , Lactoferrin/pharmacology , Lipopolysaccharides/immunology , Macrophages/drug effects , Macrophages/immunology , Mice , Mice, Inbred C57BL , Nanoparticles/therapeutic use , Pyroptosis/drug effects , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/metabolism , Treatment Outcome
20.
Viruses ; 13(10)2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438739

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.


Subject(s)
COVID-19/complications , Systemic Inflammatory Response Syndrome/physiopathology , Thrombosis/physiopathology , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Blood Coagulation Disorders/drug therapy , COVID-19/drug therapy , Endothelial Cells , Factor Xa Inhibitors/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inflammation/drug therapy , Male , Middle Aged , SARS-CoV-2/pathogenicity , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/immunology , Thrombosis/drug therapy , Thrombosis/immunology
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