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1.
Front Immunol ; 13: 841126, 2022.
Article in English | MEDLINE | ID: covidwho-1775675

ABSTRACT

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.


Subject(s)
Autoimmune Diseases , COVID-19 , Lupus Erythematosus, Systemic , Adaptor Proteins, Signal Transducing , Adenosine Triphosphatases , Adult , Autoantibodies , Autoantigens , Autoimmunity , COVID-19/complications , Child , Humans , Immunoglobulins, Intravenous , Ribonucleoproteins , Systemic Inflammatory Response Syndrome
2.
Children (Basel) ; 9(2)2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1708303

ABSTRACT

Limited data on the coagulation profile in children affected by the SARS-CoV-2 infection are available. We aimed to evaluate the role of d-dimers as predictors of poor outcomes in a pediatric population affected by the SARS-CoV-2 infection or multisystem inflammatory syndrome (MIS-C). We performed a retrospective cross-sectional multicenter study. Data from four different centers were collected. Laboratory tests, when performed, were collected at the time of diagnosis, and 24, 48, 72, 96, 120 and beyond 120 h from diagnosis; blood counts with formula, an international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimers and fibrinogen values were collected. Data regarding clinical history, management and outcome of the patients were also collected. Three hundred sixteen patients with a median age of 3.93 years (IQR 0.62-10.7) diagnosed with COVID-19 or MIS-C were enrolled. Fifty-eight patients (18.3%) showed a severe clinical outcome, 13 (4.1%) developed sequelae and 3 (0.9%) died. The univariate analysis showed that age, high D-dimer values, hyperfibrinogenemia, INR and aPTT elongation, and low platelet count were associated with an increased risk of pediatric intensive care unit (PICU) admission (p < 0.01). Three multivariate logistic regressions showed that a d-dimer level increase was associated with a higher risk of PICU admission. This study shows that D-dimer values play an important role in predicting the more severe spectrum of the SARS-CoV-2 infection, and was higher also in those that developed sequelae, including long COVID-19.

3.
Nat Med ; 2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1701612

ABSTRACT

Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.

5.
European heart journal. Case reports ; 5(12), 2021.
Article in English | EuropePMC | ID: covidwho-1601860

ABSTRACT

Background Multisystem inflammatory syndrome in children (MIS-C) is a rare life-threatening clinical condition that can develop in patients younger than 21 years of age with a history of infection/exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The cardiovascular system is a main target of the inflammatory process that frequently causes myocardial dysfunction, myopericarditis, coronary artery dilation, hypotension, and shock. Multisystem inflammatory syndrome in children-associated myocarditis is usually characterized by fever, tachycardia, non-specific electrocardiogram abnormalities, and left ventricular dysfunction, but serious tachyarrhythmias may also occur. We report two cases of patients with MIS-C-associated myocarditis who developed severe bradycardia. Case summary Two female adolescents with recent history of coronavirus disease 2019 (COVID-19) were initially hospitalized for long-lasting high-grade fever and severe gastrointestinal symptoms. Both patients were diagnosed with MIS-C-associated myocarditis for elevation of markers of myocardial injury (mean highly-sensitive cardiac troponin 2663 pg/mL, mean N-terminal-pro-brain natriuretic peptide 5097 pg/mL) and left ventricular dysfunction, which was subsequently confirmed by cardiac magnetic resonance. Both patients developed a severe sinus bradycardia (lowest heart rate 36 and 42, respectively), which appeared refractory to the treatment with intravenous Methylprednisolone and Immunoglobulins, despite a clinical and biochemical improvement. The use of Anakinra (a recombinant interleukin-1 receptor antagonist), was associated with a rapid improvement of cardiac rhythm and excellent clinical outcome at 6 months of follow-up. Discussion In patients with MIS-C-associated myocarditis, a continuous cardiac monitoring is mandatory to promptly identify potential conduction abnormalities. Adolescents may present bradycardia as a rhythm complication. We experienced a rapid recovery after treatment with Anakinra, to be considered as add-on therapy in cases refractory to standard anti-inflammatory treatment.

6.
JAMA Netw Open ; 4(12): e2139974, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1589283

ABSTRACT

Importance: Severe gastrointestinal (GI) manifestations have been sporadically reported in children with COVID-19; however, their frequency and clinical outcome are unknown. Objective: To describe the clinical, radiological, and histopathologic characteristics of children with COVID-19 presenting with severe GI manifestations to identify factors associated with a severe outcome. Design, Setting, and Participants: A multicenter retrospective cohort study (February 25, 2020, to January 20, 2021) enrolled inpatient and outpatient children (aged <18 years) with acute SARS-CoV-2 infection, confirmed by positive real-time reverse-transcriptase-polymerase chain reaction on nasopharyngeal swab or fulfilling the US Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children (MIS-C). The study was conducted by pediatricians working in primary care or hospitals in Italy participating in the COVID-19 Registry of the Italian Society of Pediatric Infectious Diseases. Main Outcomes and Measures: The occurrence of severe GI manifestations, defined by a medical and/or radiological diagnosis of acute abdomen, appendicitis (complicated or not by perforation and/or peritonitis), intussusception, pancreatitis, abdominal fluid collection, and diffuse adenomesenteritis requiring surgical consultation, occurring during or within 4 to 6 weeks after infection with SARS-CoV-2 infection. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs of factors potentially associated with severe outcomes. Results: Overall, 685 children (386 boys [56.4%]; median age, 7.3 [IQR, 1.6-12.4] years) were included. Of these children, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with MIS-C. The presence of GI symptoms was associated with a higher chance of hospitalization (OR, 2.64; 95% CI, 1.89-3.69) and intensive care unit admission (OR, 3.90; 95% CI, 1.98-7.68). Overall, 65 children (9.5%) showed severe GI involvement, including disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Twenty-seven of these 65 children (41.5%) underwent surgery. Severe GI manifestations were associated with the child's age (5-10 years: OR, 8.33; 95% CI, 2.62-26.5; >10 years: OR, 6.37; 95% CI, 2.12-19.1, compared with preschool-age), abdominal pain (adjusted OR [aOR], 34.5; 95% CI, 10.1-118), lymphopenia (aOR, 8.93; 95% CI, 3.03-26.3), or MIS-C (aOR, 6.28; 95% CI, 1.92-20.5). Diarrhea was associated with a higher chance of adenomesenteritis (aOR, 3.13; 95% CI, 1.08-9.12) or abdominal fluid collection (aOR, 3.22; 95% CI, 1.03-10.0). Conclusions and Relevance: In this multicenter cohort study of Italian children with SARS-CoV-2 infection or MIS-C, 9.5% of the children had severe GI involvement, frequently associated with MIS-C. These findings suggest that prompt identification may improve the management of serious complications.


Subject(s)
COVID-19/complications , Gastrointestinal Diseases/virology , Systemic Inflammatory Response Syndrome/complications , Child , Child, Preschool , Female , Gastrointestinal Diseases/diagnostic imaging , Gastrointestinal Diseases/pathology , Humans , Male , Prognosis , Radiography , Retrospective Studies , SARS-CoV-2
8.
Front Pediatr ; 9: 720084, 2021.
Article in English | MEDLINE | ID: covidwho-1367756

ABSTRACT

Introduction: The transmission rates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from children to adults are unclear due to a lack of controlled conditions. Materials and Methods: We investigated the occurrence of SARS-CoV-2 transmission among 12 discordant child-parent pairs in our ward. In each hospital isolation room, caregivers and children lived in close contact during the entire hospitalization period. Results: A total of 136 swab-positive children (mean age, 3.6 ± 4.9 median age, 1; IQR 0-6.2, range 0.1-17) attended by their caregivers were hospitalized. Of those, 12/136 (8.8%, mean age, 6.1 ± 5.3 median age, 4.5) were attended by caregivers who were swab and serology negative at admission despite previous close contact with positive children at home. Three children were completely dependent on their mothers, one of whom was being breastfed. The mean duration of overall exposure to the index case was 20.5 ± 8.2 days. Conclusion: None of the infected children transmitted SARS-CoV-2 infection to their caregivers, raising the hypothesis of a cluster of resistant mothers or of limited transmission from children to adults despite prolonged exposure and close contact. These data might provide reassurance regarding school openings and offer the chance of investigating SARS-CoV-2 variants in the future under the same quasi-experimental conditions.

9.
Front Pediatr ; 9: 649358, 2021.
Article in English | MEDLINE | ID: covidwho-1167356

ABSTRACT

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5-9 years and lymphopenia were statistically related to ICU admission (p < 0.05). Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission.

10.
Hosp Pediatr ; 11(3): e42-e47, 2021 03.
Article in English | MEDLINE | ID: covidwho-999866

ABSTRACT

OBJECTIVES: The paucity of symptoms and the difficulties in wearing personal protective equipment make children a potential source of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for health care workers (HCWs). Previous experience in pediatric settings reported high rate of intrahospital SARS-CoV-2 transmission in HCWs caring for children. We aimed at investigating the rate and determinants of SARS-CoV-2 infection among HCWs working in a regional reference center in the Southern Italy. METHODS: A prospective observational study was conducted to monitor the occurrence of SARS-CoV-2 infections among HCWs and investigate the relation between the infection rate and hours of exposure or number and characteristics of procedures, including nasopharyngeal swab, high-flow oxygen delivery, suctioning of airway secretions, sputum induction, and nebulizer administration. RESULTS: After 5 months of monitoring, 425.6 hours of SARS-CoV-2 exposure (18.5 hours per person), and 920 hospital procedures, no case of nosocomial transmission was reported among the 23 HCWs enrolled in the study. CONCLUSIONS: The application of stringent preventive measures, also outside the area dedicated to patients' care, can effectively control infection spreading also in pediatric settings.


Subject(s)
COVID-19/epidemiology , Disease Transmission, Infectious/prevention & control , Health Personnel , Hospital Units/statistics & numerical data , Pandemics , Personal Protective Equipment , Adult , COVID-19/transmission , Child , Female , Humans , Male , Prospective Studies , SARS-CoV-2
12.
Ital J Pediatr ; 46(1): 170, 2020 Nov 16.
Article in English | MEDLINE | ID: covidwho-926349

ABSTRACT

BACKGROUND: In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. METHODS: We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information. RESULT: Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2-9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5-19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time. CONCLUSION: An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria. The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Delivery of Health Care/organization & administration , Disease Management , Health Status , Pandemics , Pneumonia, Viral/therapy , Population Surveillance/methods , Adolescent , COVID-19 , Child , Child, Preschool , Coronavirus Infections/epidemiology , Female , Humans , Italy/epidemiology , Male , Pneumonia, Viral/epidemiology , Risk Factors , SARS-CoV-2
14.
Ital J Pediatr ; 46(1): 139, 2020 Sep 24.
Article in English | MEDLINE | ID: covidwho-791969

ABSTRACT

A statement of consensus was formulated after reviewing available literature on pediatric treatment strategies for COVID-19 by the Steering and Scientific Committee of the Italian Society of Infectious Pediatric Diseases in connection with the Italian Society of Paediatrics.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Adolescent , Age Factors , COVID-19 , Child , Child, Preschool , Consensus , Coronavirus Infections/epidemiology , Humans , Infant , Italy , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Societies, Medical
16.
Lancet Child Adolesc Health ; 4(9): 653-661, 2020 09.
Article in English | MEDLINE | ID: covidwho-613887

ABSTRACT

BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Delivery of Health Care/organization & administration , Intensive Care Units/organization & administration , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Child , Child, Preschool , Coronavirus Infections/therapy , Europe/epidemiology , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Patient Admission/trends , Pneumonia, Viral/therapy , Risk Factors , SARS-CoV-2
17.
Euro Surveill ; 25(18)2020 05.
Article in English | MEDLINE | ID: covidwho-197111

ABSTRACT

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.


Subject(s)
Chronic Disease/epidemiology , Coinfection/epidemiology , Coronavirus Infections/diagnosis , Coronavirus/isolation & purification , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Adolescent , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , COVID-19 Testing , Child , Child, Preschool , Clinical Laboratory Techniques , Coinfection/virology , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Diarrhea/etiology , Disease Outbreaks , Feces/virology , Female , Fever/etiology , Hospitals, Pediatric , Humans , Immunocompromised Host , Infant , Infant, Newborn , Italy/epidemiology , Male , Noninvasive Ventilation/methods , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Protease Inhibitors/therapeutic use , Retrospective Studies , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/therapy , Treatment Outcome
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