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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330092

ABSTRACT

The Job Syndrome or Autosomal Dominant Hyper Immunoglobulin E Syndrome (AD-HIES, LOF-STAT3 gene) is a very rare inborn error of immunity disorder with multi-organ involvement and long-life post-infective damages. Longitudinal registries are of main importance to improve knowledge on natural history and management of these rare disorders. This study aims to describe the natural history of 30 Italian patients recorded in the IPINet registry with AD-HIES, with a cumulative observational-time of 721.1 patient-years. Age at disease onset was < 12 months in the 66.7% of patients, but the mean time of diagnostic delay was 13.7 years. At diagnosis skin involvement was present in 93.3% of patients (eczema 80.8%, abscess 66.7%). At the follow up eczema was still present in 63.3% and abscess in 56.7%. Respiratory complications such as bronchiectasis and pneumatoceles were present at diagnosis in the 46.7% and 43.3% respectively. Antimicrobial prophylaxis resulted in decrease of pneumonia from 76.7–46.7%. Antifungal prophylaxis decreased mucocutaneous candidiasis occurrence from 70–56.7%. In the course of SARS-CoV-2 pandemic, seven patients developed COVID-19. Survival analyses showed that 27 out of 30 patients are still alive, while three patients died at age of 28, 39 and 46 as consequence of lungs bleeding, lymphoma and sepsis, respectively. Our study shows that many severe complications can affect AD-HIES patients. Analysis of a cumulative follow-up of 278.7 patient-years has shown that early diagnosis, adequate management at expertise centres for primary immunodeficiency, prophylactic antibiotic and antifungal therapy improve outcome and can positively influence patients’ life expectancy.

2.
Ital J Pediatr ; 48(1): 18, 2022 Feb 03.
Article in English | MEDLINE | ID: covidwho-1690896

ABSTRACT

INTRODUCTION: The incidence of acute respiratory tract infections (ARTIs) in children is difficult to estimate because they are typically treated in outpatient settings and the majority of epidemiological data originate from hospital settings and refer to the most severe illnesses. Therefore, the incidence of ARTIs in a real-world setting remains largely unexplored. Therefore, this study aims to estimate the incidence of ARTIs, upper respiratory tract infections (URTIs), and lower respiratory tract infections (LRTIs) in children aged 0-5 years in an outpatient setting. METHODS: This prospective cohort study was conducted in Lombardy, Italy, from October 1st, 2019, to March 31st, 2021, before and during the COVID-19 pandemic that began in March 2020. Caucasian healthy children aged 0-5 years were recruited from 69 Family Pediatricians (FP) and followed-up in an outpatient setting. Data were collected whenever a child was referred to FP and ARTI was diagnosed (Covid-19 related ARTI were excluded). The primary outcome was an estimate of the incidence of ARTIs. The incidence of ARTIs in different age groups and the effect of the COVID-19 pandemic on the incidence of ARTIs were secondary outcomes. RESULTS: We enrolled 484 children, 249 male (51.8%), mean age of 2.39 ± 1.68 years. The mean estimated incidence of ARTIs was 12.1/100 children × 30 days (95% CIs: 9.5-12.9), with the highest value observed in infants aged 1-12 months (24.9/100 children × 30 days; 95% CIs: 17.6-28.9). The mean estimated incidence of URTIs was higher than that of LRTIs (8.3 - CIs: 7.6-8.9 vs 3.8/100 children × 30 days - CIs: 6.4-4.3, respectively). The comparison of ARTIs, which occurred in the pre-pandemic winter, to those measured during the COVID-19 pandemic, revealed an impressive 82.1% drop in the incidence rate (CIs: 77.8-85.7). CONCLUSIONS: This study showed that infants aged 1-12 months are more likely to develop ARTIs than older children and that COVID-19 pandemic has dramatically altered the epidemiology of ARTIs in children aged 0-5 years.


Subject(s)
COVID-19 , Respiratory Tract Infections , Acute Disease , Adolescent , Child , Child, Preschool , Humans , Incidence , Infant , Infant, Newborn , Male , Outpatients , Pandemics , Prospective Studies , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , SARS-CoV-2
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323262

ABSTRACT

Background: Severe gastrointestinal (GI) involvement has been occasionally reported in children with SARS-CoV-2 infection or among those with multisystem inflammatory syndrome (MIS-C). We aimed to investigate the clinical, radiological and histopathological GI characteristics in order to identify factors associated with severe outcome.Methods: In this multicenter retrospective nationwide cohort study, symptomatic children with laboratory confirmed SARS-CoV-2 infection or MIS-C were enrolled. Children who received a diagnosis of acute abdomen, appendicitis, intussusception, pancreatitis, diffuse adeno-mesenteritis or abdominal fluid collections requiring surgical consultation and temporally correlated with SARS-CoV-2 infection were classified as having a severe GI involvement. Logistic regression models were used to estimate odds ratios (OR [95% confidence intervals]) between potential explanatory factors and severe outcome.Findings: 685 children were enrolled between February 2020 and January 2021. The presence of GI symptoms was associated with a higher chance of hospital admission (OR 2·64 [1·89–3·69]) and of intensive care support (OR 3·90 [1·98–7·68]).Overall, 65 children (9.5%) showed a severe GI involvement featuring atypical presentations including disseminated adeno-mesenteritis (39·6%), appendicitis (33·5%), abdominal fluid collections (21·3%), pancreatitis (6·9%) or ileal intussusception (4·6%). Twenty-seven (42%) of these children underwent surgery, and remarkably only half of clinically suspected appendicitis were histologically confirmed. Children aged 5-10 years (OR 8·33 [2·62–26·5]) or > 10 years of age (OR 6·37 [2·12-19·1]) had a higher chance of severe outcome, compared to preschool-age children. Severe GI outcomes were more frequent in patients with abdominal pain (aOR 34·5 [10·1–118]), lymphopenia (aOR 8·93 [3·03-26·3]) or MIS-C (aOR 6·28 [1·92–20·5]). Diarrhea was associated with a higher chance of adeno-mesenteritis (aOR 3·13 [1·08–9·12]) and abdominal fluid collections (aOR 3·22 [1·03-10]).Interpretation: About 10% of symptomatic children with COVID-19 may have severe GI involvement, frequently associated with MIS-C. Early identification of at-risk patients can improve the management of serious complications.Funding Statement: None.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study protocol was approved by the Ethical Committee of the coordinating center (protocol number 0031296) as well as by independent ethics committees and/or institutional review boards of any single enrolling center.

4.
J Nephrol ; 35(3): 745-759, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1650680

ABSTRACT

BACKGROUND: Dialysis and kidney transplant patients with moderate-severe COVID-19 have a high mortality rate, around 30%, that is similar in the two populations, despite differences in their baseline characteristics. In these groups, the immunology of the disease has been poorly explored. METHODS: Thirty-two patients on dialysis or with kidney transplant and SARS-CoV-2 infection requiring hospitalization (COV group) were included in our study. Lymphocyte subsets, dendritic cell (DC) counts and monocyte activation were studied. SARS-CoV-2 anti-spike/anti-nucleocapsid were monitored, and baseline cytokines and chemokines were measured in 10 patients. RESULTS: The COV group, compared to healthy subjects and uninfected dialysis/kidney transplant controls, showed lower numbers of CD4 + and CD8 + T cells, Natural-Killer (NK), B cells, plasmacytoid and myeloid DCs, while the proportion of terminally differentiated B-cells was increased. IL6, IL10, IFN-α and chemokines involved in monocyte and neutrophil recruitment were higher in the COV group, compared to uninfected dialysis/kidney transplant controls. Patients with severe disease had lower CD4 + , CD8 + and B-cell counts and lower monocyte HLA-DR expression. Of note, when comparing dialysis and kidney transplant patients with COVID-19, the latter group presented lower NK and pDC counts and monocyte HLA-DR expression. Up to 60 days after symptom onset, kidney transplant recipients showed lower levels of anti-spike antibodies compared to dialysis patients. CONCLUSIONS: During SARS-CoV-2 infection, dialysis and kidney transplant patients manifest immunophenotype abnormalities; these are similar in the two groups, however kidney transplant recipients show more profound alterations of the innate immune system and lower anti-spike antibody response.


Subject(s)
COVID-19 , Kidney Transplantation , HLA-DR Antigens , Humans , Kidney Transplantation/adverse effects , Renal Dialysis/adverse effects , SARS-CoV-2 , Transplant Recipients
5.
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
6.
Infection ; 2021 Dec 07.
Article in English | MEDLINE | ID: covidwho-1555289

ABSTRACT

PURPOSE: To describe the clinical course of COVID-19 in patients with cystic fibrosis (CF) and to identify risk factors for severe COVID-19. METHODS: We conducted a prospective study within the Italian CF Society. CF centers collected baseline and follow-up data of patients with virologically confirmed SARS-CoV-2 infection between March 2020 and June 2021. Odds ratios (ORs) for severe SARS-CoV-2 (as defined by hospital admission) were estimated by logistic regression models. RESULTS: The study included 236 patients with positive molecular test for SARS-CoV-2. Six patients died, 43 patients were admitted to hospital, 4 admitted to intensive care unit. Pancreatic insufficiency was associated with increased risk of severe COVID-19 (OR 4.04, 95% CI 1.52; 10.8). After adjusting for age and pancreatic insufficiency, forced expiratory volume in one second (FEVp) < 40% (OR 4.54, 95% CI 1.56; 13.2), oxygen therapy (OR 12.3, 95% CI 2.91-51.7), underweight (OR 2.92, 95% CI 1.12; 7.57), organ transplantation (OR 7.31, 95% CI 2.59; 20.7), diabetes (OR 2.67, 95% CI 1.23; 5.80) and liver disease (OR 3.67, 95% CI 1.77; 7.59) were associated with increased risk of severe COVID-19, while use of dornase alfa was associated with a reduced risk (OR 0.34, 95% CI 0.13-0.88). No significant changes were observed in FEVp from baseline to a median follow-up of 2 months (median difference: 0, interquartile range: - 4; 5, P = 0.62). CONCLUSION: Clinical features indicative of severe form of CF are associated with increased risk of COVID-19 hospitalization. SARS-CoV-2 infected patients do not experience a deterioration of respiratory function.

7.
Front Pediatr ; 9: 645063, 2021.
Article in English | MEDLINE | ID: covidwho-1526780

ABSTRACT

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, data registered in the European countries revealed increasing cases of infection in cystic fibrosis (CF) patients. In the course of this pandemic, we enrolled 17 CF patients for a study evaluating inflammatory markers. One of them developed COVID-19, giving us the possibility to analyze inflammatory markers in the acute phase as compared to levels detected before and after the infectious episode and to levels measured in the other CF patients enrolled to the study who did not experience COVID-19 and 23 patients referred to our center for SARS-CoV-2 infection.

10.
Front Immunol ; 12: 654587, 2021.
Article in English | MEDLINE | ID: covidwho-1348485

ABSTRACT

Background: SARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD). Objective: With this study we aimed to shed new light on the pathogenesis of these two SARS-CoV-2-related clinical manifestations. Methods: We investigated lymphocyte and dendritic cells subsets, chemokine/cytokine profiles and evaluated the neutrophil activity mediators, myeloperoxidase (MPO), and reactive oxygen species (ROS), in 10 children with COVID-19 and 9 with MIS-C at the time of hospital admission. Results: Patients with MIS-C showed higher plasma levels of C reactive protein (CRP), MPO, IL-6, and of the pro-inflammatory chemokines CXCL8 and CCL2 than COVID-19 children. In addition, they displayed higher levels of the chemokines CXCL9 and CXCL10, mainly induced by IFN-γ. By contrast, we detected IFN-α in plasma of children with COVID-19, but not in patients with MIS-C. This observation was consistent with the increase of ISG15 and IFIT1 mRNAs in cells of COVID-19 patients, while ISG15 and IFIT1 mRNA were detected in MIS-C at levels comparable to healthy controls. Moreover, quantification of the number of plasmacytoid dendritic cells (pDCs), which constitute the main source of IFN-α, showed profound depletion of this subset in MIS-C, but not in COVID-19. Conclusions: Our results show a pattern of immune response which is suggestive of type I interferon activation in COVID-19 children, probably related to a recent interaction with the virus, while in MIS-C the immune response is characterized by elevation of the inflammatory cytokines/chemokines IL-6, CCL2, and CXCL8 and of the chemokines CXCL9 and CXL10, which are markers of an active Th1 type immune response. We believe that these immunological events, together with neutrophil activation, might be crucial in inducing the multisystem and cardiovascular damage observed in MIS-C.


Subject(s)
COVID-19/immunology , Chemokine CXCL10/immunology , Chemokine CXCL9/immunology , Dendritic Cells/immunology , Interferon-gamma/immunology , Plasma Cells/immunology , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies
11.
PLoS One ; 16(5): e0251527, 2021.
Article in English | MEDLINE | ID: covidwho-1226898

ABSTRACT

OBJECTIVE: To describe the symptoms and clinical course of SARS-CoV-2 infection in patients with cystic fibrosis (CF). METHODS: We carried out a prospective multicentre cohort study based on 32 CF centres and 6597 patients. Centres were contacted to collect baseline and follow-up data of patients who reported symptoms suggestive of COVID-19 or who had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls). RESULTS: Thirty patients were reported from the centres, 16 of them tested positive and 14 tested negative. No differences in symptoms and outcome of the disease were observed between groups. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms. Eight cases (50%) were hospitalized but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation, none required ICU admission and all patients fully recovered without short-term sequelae. CONCLUSIONS: The course of SARS-CoV-2 in our patients was relatively favorable. However, COVID-19 should not be considered a mild disease in CF patients, particularly for those with severely impaired respiratory function and organ transplant.


Subject(s)
COVID-19/complications , Cystic Fibrosis/complications , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Cystic Fibrosis/therapy , Disease Management , Female , Hospitalization , Humans , Italy/epidemiology , Male , Prospective Studies , SARS-CoV-2/isolation & purification , Young Adult
12.
Front Immunol ; 11: 580987, 2020.
Article in English | MEDLINE | ID: covidwho-914428

ABSTRACT

Covid-19 features a delayed onset of critical illness occurring approximately one week from the beginning of symptoms, which corresponds to the bridging of innate and adaptive immunity. We reasoned that the immune events occurring at the turning point of disease might mark the direction toward pathogenic versus protective inflammatory responses. Subjects with either severe (s; PaO2/FiO2 ratio <200) or mild (m; PaO2/FiO2 ratio>300) Covid-19 were enrolled. A range of chemokines and cytokines as well as reactive oxygen species (ROS) were measured in plasma. Dendritic and NK cell frequency, monocyte and B-/T-cell phenotype and SARS-CoV-2-specific T-cell responses were assessed in PBMC. Twenty mCovid-19 and 20 sCovid-19 individuals were studied. sCovid-19 patients displayed higher non-classical monocytes, plasma chemokines (CXCL8, CXCL9, CXCL10), cytokines (IL-6, IL-10), and ROS versus mCovid-19. sCovid-19 also showed significantly increased activated CD38+HLA-DR+ T-lymphocyte, and granzyme-B+/perforin+ pro-cytolytic T-cells. All Covid-19 patients showed SARS-CoV-2 specific-T-cell response with a predominance of Th1 bi- or trifunctional IFN-γ/IL-2/TNF-α-expressing CD4+, while no difference according to disease severity was observed. Severe Covid-19 features heightened circulating IFN-inducible chemokines and activated pro-cytolytic Th1 cell phenotype in the second week of illness, yet SARS-CoV-2-specific responses are similar to that of mild illness. Altogether, our observations suggest Th1 polarization coupled to higher cytolytic profile in sCovid-19 as correlate of disease pathogenesis and as potential targets to be investigated in the roadmap to therapy and vaccine development.


Subject(s)
COVID-19/blood , Chemokines/blood , Interferons/blood , Leukocytes, Mononuclear/immunology , SARS-CoV-2/physiology , Th1 Cells/immunology , Aged , COVID-19/immunology , COVID-19/virology , Female , Humans , Male , Middle Aged , Phenotype , SARS-CoV-2/genetics
13.
J Allergy Clin Immunol ; 147(2): 520-531, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-792893

ABSTRACT

BACKGROUND: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. OBJECTIVE: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. METHODS: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. RESULTS: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. CONCLUSIONS: This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.


Subject(s)
COVID-19/epidemiology , Genetic Diseases, Inborn/epidemiology , Immunologic Deficiency Syndromes/epidemiology , SARS-CoV-2 , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Retrospective Studies , Risk Factors , Severity of Illness Index , Young Adult
14.
Eur J Immunol ; 50(9): 1412-1414, 2020 09.
Article in English | MEDLINE | ID: covidwho-615368

ABSTRACT

Study of immunological features of immune response in 14 children (aged from 12 days up to 15 years) and of 10 adults who developed COVID-19 show increased number of activated CD4 and CD8 cells expressing DR and higher plasmatic levels of IL-12 and IL-1ß in adults with COVID-19, but not in children. In addition, plasmatic levels of CCL5/RANTES are higher in children and adults with COVID-19, while CXCL9/MIG was only increased in adults. Higher number of activated T cells and expression of IL-12 and CXCL9 suggest prominent Th1 polarization of immune response against SARS-CoV2 in infected adults as compared with children.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , Chemokines/blood , SARS-CoV-2/immunology , Adolescent , COVID-19/immunology , COVID-19/pathology , Chemokine CCL2/blood , Chemokine CCL5/blood , Chemokine CXCL10/blood , Chemokine CXCL9/blood , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Interleukin-8/blood , Lymphocyte Activation , Lymphocyte Count , Lymphopenia/pathology , Male , T-Lymphocyte Subsets/immunology
15.
J Neuroimmunol ; 345: 577282, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-437267

ABSTRACT

A multiple sclerosis patient infected by SARS-CoV-2 during fingolimod therapy was hospitalized with moderate clinical features, and recovered in 15 days. High levels of CCL5 and CCL10 chemokines and of antibody-secreting B cells were detected, while the levels other B- and T-cell subsets were comparable to that of appropriate controls. However, CD4+ and CD8+ cells were oligoclonally expanded and prone to apoptosis when stimulated in vitro. This study suggests that fingolimod-immunosuppressed patients, despite the low circulating lymphocytes, may rapidly expand antibody-secreting cells and mount an effective immune response that favors COVID-19 recovery after drug discontinuation.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/immunology , Immunocompromised Host , Multiple Sclerosis, Relapsing-Remitting/immunology , Multiple Sclerosis, Relapsing-Remitting/virology , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Betacoronavirus , COVID-19 , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Pandemics , SARS-CoV-2
16.
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
17.
Pediatr Allergy Immunol ; 31(5): 565-569, 2020 07.
Article in English | MEDLINE | ID: covidwho-102307

ABSTRACT

BACKGROUND: The recent SARS-CoV-2 pandemic, which has recently affected Italy since February 21, constitutes a threat to normal subjects, as the coronavirus disease-19 (COVID-19) can manifest with a broad spectrum of clinical phenotypes ranging from asymptomatic cases to pneumonia or even death. There is evidence that older age and several comorbidities can affect the risk to develop severe pneumonia and possibly the need of mechanic ventilation in subjects infected with SARS-CoV-2. Therefore, we evaluated the outcome of SARS-CoV-2 infection in patients with inborn errors of immunity (IEI) such as X-linked agammaglobulinemia (XLA). METHODS: When the SARS-CoV-2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS-CoV-2 search by nasopharyngeal swab in patients presenting with symptoms that could be a manifestation of COVID-19, such as fever, cough, diarrhea, or vomiting. RESULTS: We describe two patients with X-linked agammaglobulinemia (XLA) aged 34 and 26 years with complete absence of B cells from peripheral blood who developed COVID-19, as diagnosed by SARS-CoV-2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough, and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care. CONCLUSION: Our report suggests that XLA patients might present with high risk to develop pneumonia after SARS-CoV-2 infection, but can recover from infection, suggesting that B-cell response might be important, but is not strictly required to overcome the disease. However, there is a need for larger observational studies to extend these conclusions to other patients with similar genetic immune defects.


Subject(s)
Agammaglobulinemia/complications , Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Genetic Diseases, X-Linked/complications , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Adult , Agammaglobulinemia/therapy , Anti-Bacterial Agents/therapeutic use , COVID-19 , Enzyme Inhibitors/therapeutic use , Genetic Diseases, X-Linked/therapy , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive/methods , Italy , Male , Pandemics , SARS-CoV-2 , Treatment Outcome
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