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1.
Front Genet ; 13: 896749, 2022.
Article in English | MEDLINE | ID: covidwho-2009858

ABSTRACT

Background: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive ribosomopathy mainly characterized by exocrine pancreatic insufficiency, skeletal alterations, neutropenia, and a relevant risk of hematological transformation. At least 90% of SDS patients have pathogenic variants in SBDS, the first gene associated with the disease with very low allelic heterogeneity; three variants, derived from events of genetic conversion between SBDS and its pseudogene, SBDSP1, provided the alleles observed in about 62% of SDS patients. Methods: We performed a reanalysis of the available WES files of a group of SDS patients with biallelic SBDS pathogenic variants, studying the results by next bioinformatic and protein structural analysis. Parallelly, careful clinical attention was given to the patient focused in this study. Results: We found and confirmed in one SDS patient a germline heterozygous missense variant (c.100T>C; p.Phe34Leu) in the EIF6 gene. This variant, inherited from his mother, has a very low frequency, and it is predicted as pathogenic, according to several in silico prediction tools. The protein structural analysis also envisages the variant could reduce the binding to the nascent 60S ribosomal. Conclusion: This study focused on the hypothesis that the EIF6 germline variant mimics the effect of somatic deletions of chromosome 20, always including the locus of this gene, and similarly may rescue the ribosomal stress and ribosomal dysfunction due to SBDS mutations. It is likely that this rescue may contribute to the stable and not severe hematological status of the proband, but a definite answer on the role of this EIF6 variant can be obtained only by adding a functional layer of evidence. In the future, these results are likely to be useful for selected cases in personalized medicine and therapy.

2.
J Adolesc Young Adult Oncol ; 11(3): 316-319, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1890824

ABSTRACT

Worldwide, the coronavirus 19 disease pandemic caused a worse chance of a timely diagnosis for cancer patients. We conducted a retrospective analysis of new diagnoses registered in the national pediatric oncology database, comparing the first lockdown period (March-May 2020) with the same period of 2015-2019. The total number of cases (0-19 years) dropped by 20.8% (from 441 between 2015 and 2019 to 349 in 2020). A major reduction was observed for adolescents (15-19 years) (-32.9%) and for adolescents with solid tumors (-56.4%, p = 0.03). Our data suggest that the enforced lockdown reduced the possibility for these already vulnerable patients to access the referral centers.


Subject(s)
COVID-19 , Neoplasms , Adolescent , COVID-19/epidemiology , Child , Communicable Disease Control , Delayed Diagnosis , Humans , Neoplasms/diagnosis , Neoplasms/epidemiology , Pandemics , Retrospective Studies
3.
Clin Infect Pract ; 15: 100144, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1803778

ABSTRACT

Background: Sars-CoV2 can cause severe pneumonia and acute respiratory distress syndrome (ARDS). In COVID-19-associated respiratory failure, lung transplantation might be an option (Bharat A). Case report: A previously healthy 63-year-old man with a nasopharyngeal swab positive for SarsCoV2 and radiological evidence of interstitial lung consolidations developed acute respiratory distress that required intubation and veno-venous extracorporeal membrane oxygenation support (VV ECMO). Because of no recovery of his lung function, he underwent a bilateral lung transplant. ICU stay was complicated by several episodes of bacterial superinfections and an increase of liver function tests (LFTs). Afterward, he faced a progressive clinical worsening associated to severe anemia, further rise of indices of cholestasis, hypertriglyceridemia and hyperferritinemia. Bone marrow smear showed a picture compatible with haemophagocytic lymphohistocytosis (HLH) and first and second line therapy were started. In addition, a transjugular hepatic biopsy was performed with histopathological evidence of portal and periportal fibrosis, compatible with Covid 19-related cholangiopathy. During the hospital stay, he developed several MDR opportunistic infections. The patient died few months later from multiorgan failure secondary to septic shock. A post-mortem confirmed a diagnosis of cholangiopathy, and medullary erythro-haemophagocytosis. Conclusion: Post Covid19 syndrome is a clinical entity that includes novel and old sequelae following recovery from Sars-CoV2 infections. Early identification of these diseases is crucial for adequate management and might influence the long term prognosis of these patients.

4.
J Cell Mol Med ; 26(9): 2520-2528, 2022 05.
Article in English | MEDLINE | ID: covidwho-1769729

ABSTRACT

Although numerous patient-specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalassaemic syndromes in COVID-19 patients remains poorly understood. We studied the outcomes of 137 COVID-19 patients with a history of transfusion-dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalassaemia. The mean age of thalassaemia patients included in our study was 41 ± 16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 40% of thalassaemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID-19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age-, sex- and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in-hospital complications (supplemental oxygen use, admission to an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassaemia group compared to the matched cohort with no history of thalassaemia. Amongst thalassaemia patients in general, the TIT group exhibited a higher rate of hospitalization compared to the TDT group (p = 0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the TIT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in-hospital, all-cause mortality, whereas the presence of thalassaemia (either TDT or TIT) was found to be independently associated with reduced all-cause mortality. The presence of thalassaemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models.


Subject(s)
COVID-19 , Iron Overload , Thalassemia , COVID-19/complications , Female , Hospitals , Humans , Iron Overload/etiology , Male , Oxygen , Registries , Thalassemia/complications , Thalassemia/therapy
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309933

ABSTRACT

Background: Although numerous patient specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalasemic syndromes in COVID-19 patients remains poorly understood.Aims: We studied the outcomes of 137 COVID-19 patients with a history of Transfusion Dependent Thalassemia (TDT) and non-Transfusion Dependent Thalassemia (NTDT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalasemia.Results: The mean age of thalassemia patients included in our study was 41±16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 25% of thalassemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID-19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age-, sex- and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in-hospital complications (supplemental oxygen use, admission to the an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassemia group compared to the matched cohort with no history of thalassemia. Amongst thalassemia patients in general, the NTDT group exhibited a higher rate of hospitalization compared to the TDT group (p=0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the NTDT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in-hospital, all-cause mortality, whereas the presence of thalassemia (either TDT or NTDT) was found to be independently associated with reduced all-cause mortality.Conclusions: The presence of thalassemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models.Trial Registration for sources of data extraction: NCT: 04334291, 04746066Funding Statement: This study was funded by a non-conditioned grant from FUNDACIÓN INTERHOSPITALARIA PARA LA INVESTIGACIÓN CARDIOVASCULAR, FIC. (Madrid, Spain). This nonprofit institution had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the paper for publication.Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the Ethics Committees in all of the centers involved (Banjarmasin, Bari, Cagliari, Catania, Ferrara, Gela, Genoa, Getafe, Guadalajara, Legan, Madrid, Mannheim, Milan, Monza, Naples, Olbia, Padua, Pavia, Ragusa, Rome, Salerno, Turin, Valladolid and Verona).

6.
Ital J Pediatr ; 48(1): 7, 2022 Jan 12.
Article in English | MEDLINE | ID: covidwho-1634416

ABSTRACT

The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options.The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors.Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron).These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children.AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories.Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts' agreement.This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Patient Selection , Adolescent , Age Factors , COVID-19/complications , Child , Consensus , Drug Combinations , Humans , Italy , Risk Factors , Societies, Medical
8.
Stem Cells Transl Med ; 10(4): 636-642, 2021 04.
Article in English | MEDLINE | ID: covidwho-921740

ABSTRACT

Anti-inflammatory and immune-modulatory therapies have been proposed for the treatment of COVID-19 and its most serious complications. Among others, the use of mesenchymal stromal cells (MSCs) is under investigation given their well-documented anti-inflammatory and immunomodulatory properties. However, some critical issues regarding the possibility that MSCs could be infected by the virus have been raised. Angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) are the main host cell factors for the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), entry, but so far it is unclear if human MSCs do or do not express these two proteins. To elucidate these important aspects, we evaluated if human MSCs from both fetal and adult tissues constitutively express ACE2 and TMPRSS2 and, most importantly, if they can be infected by SARS-CoV-2. We evaluated human MSCs derived from amnios, cord blood, cord tissue, adipose tissue, and bone marrow. ACE2 and TMPRSS2 were expressed by the SARS-CoV-2-permissive human pulmonary Calu-3 cell line but not by all the MSCs tested. MSCs were then exposed to SARS-CoV-2 wild strain without evidence of cytopathic effect. Moreover, we also excluded that the MSCs could be infected without showing lytic effects since their conditioned medium after SARS-CoV-2 exposure did not contain viral particles. Our data, demonstrating that MSCs derived from different human tissues are not permissive to SARS-CoV-2 infection, support the safety of MSCs as potential therapy for COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , COVID-19/immunology , Gene Expression Regulation/immunology , Mesenchymal Stem Cells/immunology , SARS-CoV-2/immunology , Serine Endopeptidases/immunology , Cells, Cultured , Humans
9.
Ital J Pediatr ; 46(1): 142, 2020 Oct 02.
Article in English | MEDLINE | ID: covidwho-810379

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting. METHODS: We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment. RESULTS: The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians. CONCLUSIONS: Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications.


Subject(s)
Coronavirus Infections/prevention & control , Infection Control/organization & administration , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Quarantine/organization & administration , Surveys and Questionnaires , Telemedicine/statistics & numerical data , Adult , Ambulatory Care/statistics & numerical data , COVID-19 , Child , Coronavirus Infections/epidemiology , Delivery of Health Care/organization & administration , Emergency Service, Hospital/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Italy , Male , Outcome Assessment, Health Care , Pandemics/statistics & numerical data , Patient Care Planning/organization & administration , Pediatrics/methods , Pneumonia, Viral/epidemiology , Societies, Medical
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