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1.
Sci Rep ; 11(1): 23394, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862409

RESUMO

Tuberculosis (TB) incidence should decline by 20% in the Europe in 2015-2020, in line with End-TB milestones. We retrospectively evaluated TB notifications in the province of Brescia from 2004 to 2020. Cases were classified per patient origin and entitlement to Health Assistance for foreign born people: Italians (ITA), Foreigners permanently entitled (PEF) or Temporarily Entitled (TEF) to Health Regional Assistance. Poisson regression analysis was performed to assess associations between incidence and age, sex, continent of origin and year of notification. Overall 2279 TB cases were notified: 1290 (56.6%) in PEF, 700 (30.7%) in ITA and 289 (12.7%) in TEF. Notifications declined from 15.2/100,000 in 2004 to 6.9/100,000 in 2020 (54.6% reduction, temporary increase in 2013-2018 for TEF). Age (Incidence Risk Ratio, IRR, 1.02, 1.019-1.024 95%CI), sex (IRR 1.22, 1.12-1.34 95%CI), and continent of origin were positively associated with notifications (IRR 34.8, 30.8-39.2 95%CI for Asiatic, and IRR 20.6, 18.1-23.4 95%CI for African origin), p < 0.001. Notification decline was sharper in 2020, especially among TEF. End-TB milestone for 2020 was reached, but foreigners continue to represent a high risk group for the disease. Discontinuation of services due to the COVID-19 pandemic was associated with a sharp decrease in TB notification in 2020.

2.
JAC Antimicrob Resist ; 3(4): dlab188, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34909691

RESUMO

Objectives: To describe our real-life experience with cefiderocol in XDR and difficult-to-treat resistant Pseudomonas aeruginosa (DTR-P) infections without any other available treatment options. Methods: We included patients with a proven infection due to an XDR/DTR-P, who had failed on previous regimens, and were treated with cefiderocol, following them prospectively to day 90 or until hospital discharge or death. Results: Seventeen patients treated for >72 h with cefiderocol were included: 14 receiving combination regimens (82.4%) and 3 receiving monotherapy (17.6%). Fourteen patients were males (82%) with a median age of 64 years (IQR 58-73). Fifteen patients (88.2%) were admitted to the ICU and five had septic shock (29%). Seven cases (41.2%) were ventilator-associated pneumonia, of which 71% (5/7) occurred in COVID-19 patients. Four were complicated intrabdominal infections, one ecthyma gangrenosum, one nosocomial pneumonia and one empyema, one osteomyelitis, one primary bacteraemia, and one nosocomial external ventricular drainage meningitis. Clinical cure and microbiological cure rates were 70.6% and 76.5%, respectively. There were six deaths (35.3%) after a median of 8 days (IQR 3-10) from the end of treatment, but only two of them (11.7%) were associated with P. aeruginosa infection progression. Conclusions: Our experience collecting this large case series of DTR-P treated with cefiderocol may help clinicians consider this new option in this hard-to-manage setting. Our results are even more relevant in the current scenario of ceftolozane/tazobactam shortage. Importantly, this is the first study providing real-life data indicating adequate cefiderocol concentrations in CSF.

3.
Pharmaceuticals (Basel) ; 14(12)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34959672

RESUMO

Monoclonal antibodies (mAbs) have been known since the 1970s. However, their therapeutic potential in the medical field has recently emerged, with the advancement of manufacturing techniques. Initially exploited mainly in the oncology field, mAbs have become increasingly relevant in Infectious Diseases. Numerous mAbs have been developed against SARS-CoV 2 and have proven their effectiveness, especially in the management of the mild-to-moderate disease. In this review, we describe the monoclonal antibodies currently authorized for the treatment of the coronavirus disease 19 (COVID-19) and offer an insight into the clinical trials that led to their approval. We discuss the mechanisms of action and methods of administration as well as the prophylactic and therapeutic labelled indications (both in outpatient and hospital settings). Furthermore, we address the critical issues regarding mAbs, focusing on their effectiveness against the variants of concern (VoC) and their role now that a large part of the population has been vaccinated. The purpose is to offer the clinician an up-to-date overview of a therapeutic tool that could prove decisive in treating patients at high risk of progression to severe disease.

4.
Pathogens ; 10(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34832520

RESUMO

In 2021 the scientific community's efforts have been focused on solving the back-breaking challenge of the COVID-19 pandemic, but sexually transmitted infections (STI) are still one of the most common global health problems. Syphilis is a systemic disease caused by the spirochaete Treponema pallidum (TP) and is one of the oldest known diseases. Its incidence has increased in the last few years and syphilis still remains a contemporary plague that continues to afflict millions of people worldwide. Despite research improvements, syphilis pathogenesis is not completely clear; clinical presentation is very heterogeneous and the diagnosis can sometimes be difficult. Furthermore, few therapeutic options are available, and a vaccine has not been found yet. In this review, we describe the most recent evidence concerning the clinical manifestation, diagnosis, treatment and vaccine prospectives for this disease.

5.
Medicine (Baltimore) ; 100(45): e27732, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766580

RESUMO

RATIONALE: HIV elite controllers represent a rare subset of persons living with HIV, able to spontaneously control viral replication without antiviral therapy. HLA-B∗57 and HLA-B∗27 alleles are associated to efficient polyfunctional CD8+ T-cell response and are overrepresented in elite controllers but these alleles alone incompletely explain spontaneous HIV replication control in these subjects. Further mechanisms involved in innate and adaptive immune response and host genetics may contribute to this control. In this context, the homeostatic iron regulator (HFE) gene encodes a major histocompatibility complex-class-I-like molecule involved in both innate immunity, acting also through autophagy regulation, and iron homeostasis, strictly related to immune functions and susceptibility to infections. PATIENT CONCERNS: Homozygousity for the p.His63Asp (H63D) variant in the HFE gene was identified in an 80-year-old HIV-infected woman with spontaneous control of viral replication. DIAGNOSIS: HIV-1 RNA was undetectable in patient's serum with a routine assay and an ultra-sensitive assay (<1 copy/mL) during the 30 years follow-up. CD4+ and CD8+ T cell counts were stable and normal during all this period. INTERVENTIONS: The patient had a history of absence of any physical ailment and no antiviral therapy has been prescribed during the 30 years of follow-up. The subject did not harbor HLA-B∗57 and HLA-B∗27 alleles. HFE gene was sequenced by Sanger, as part of a larger study on a cohort of HIV infected patients, aged >65 years and screened for polymorphisms in genes belonging to several pathways involved in neuroinflammation. OUTCOMES: The woman had CD4+ and CD8+ T cell normal values and spontaneously controlled serum HIV-1 RNA levels for 30 years. LESSONS: We assume that the interplay between the HFE H63D variant in homozygosity and innate immunity, perhaps through autophagy regulation, could play a role in HIV-1 replication control in our patient. This hypothesis needs to be explored in in vitro and in vivo studies. Understanding mechanisms involved in spontaneous control of HIV-1 replication remains indeed a challenge due to its possible implications for HIV cure research.

6.
Travel Med Infect Dis ; 44: 102196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34748988

RESUMO

BACKGROUND: Severe imported pediatric malaria is of concern in non-endemic settings. We aimed to determine the features of pediatric severe cases in order to design a model able to stratify patients at presentation. METHODS: We conducted a retrospective cross-sectional study including all imported P. falciparum malaria infection in patients ≤14 years of age, treated from January 2008 to February 2019 in two tertiary hospitals: Brescia, Italy and Barcelona, Spain. Severe malaria was defined according to World Health Organization criteria. Mortality rate, pediatric intensive care unit (PICU) stay and blood transfusion were analysed as adverse outcomes. RESULTS: Out of 139 children included, 30.9% were severe malaria. Twenty-seven (19.4%) were admitted to PICU, and transfusion was required in 14 cases (10.1%). Predictors for severe malaria were: young age, low hemoglobin, high white blood cells (WBC) and high C-reactive protein. Platelet <130,000/µl correlated with severe malaria (without statistical significance). A model that includes age, WBC and C-reactive protein shows a high specificity to classify patients without severe malaria (92.3%) with 70% PPV and 75% NPV. CONCLUSIONS: A score based on patient's age, WBC and C-reactive protein easily available at emergency room can help to identify children with higher risk of adverse outcomes.

8.
PLoS One ; 16(10): e0258533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644336

RESUMO

OBJECTIVE: To investigate the durability of the first integrase inhibitor-based regimen in a HIV geriatric multicentric prospective cohort and to explore the reasons of regimen discontinuation. DESIGN: This is an analysis conducted on the Geriatric Patients Living with HIV/AIDS (GEPPO) cohort, an Italian prospective observational multicentre cohort of people living with HIV with 65 years of age or more. METHODS: The analysis was performed using R (version 4.0.2). The tests performed were two sided assuming a 5% significance level (Kruskal-Wallis test, Chi-squared test, log-rank test and a Cox Proportional Hazard model). The proportion of participants discontinuing the three regimens was displayed using cumulative curves. RESULTS: Among 1531 patients enrolled between 2017 and 2019 in the GEPPO cohort, we included 822 participants in this analysis. At baseline, median age was 69.8, the immunovirological profile good, multimorbidity was present in 42.3% of participants, while 27.4% were on polypharmacy. Overall, 483, 243 and 96 participants received DTG, RAL and EVG/c respectively as first InSTI. At the end of the follow up 6.4%, 21.1% and 22.9% participants discontinued DTG, RAL and EVG/c respectively. Using a log-rank test, EVG showed a significantly lower durability than DTG (p<0.001) or RAL (p 0.05) or both, DTG and RAL (p<0.001). Among participants who discontinued their regimen we found 0 virological failure and 56.7% simplification/deprescription. CONCLUSIONS: The three integrase inhibitors considered showed a good durability and no virological failures in geriatric patients such as those enrolled in the GEPPO cohort when used in a two or three drug regimen.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Idoso , Amidas/uso terapêutico , Antirretrovirais/uso terapêutico , Quimioterapia Combinada , Feminino , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Estudos Longitudinais , Masculino , Adesão à Medicação , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Polimedicação , Modelos de Riscos Proporcionais , Estudos Prospectivos , Piridonas/uso terapêutico , Quinolonas/uso terapêutico , Raltegravir Potássico/uso terapêutico , Resultado do Tratamento
9.
Biomolecules ; 11(10)2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34680118

RESUMO

Gastrointestinal cancers, particularly colorectal cancer, are mainly influenced by the dietary factor. A diet rich in fruits and vegetables can help to reduce the incidence of colorectal cancer thanks to the phenolic compounds, which possess antimutagenic and anticarcinogenic properties. Polyphenols, alongside their well-known antioxidant properties, also show a pro-oxidative potential, which makes it possible to sensitize tumor cells to oxidative stress. HO-1 combined with antioxidant activity, when overexpressed in cancer cells, is involved in tumor progression, and its inhibition is considered a feasible therapeutic strategy in cancer treatment. In this study, the effects of protocatechuic acid (PCA) on the viability of colon cancer cells (CaCo-2), annexin V, LDH release, reactive oxygen species levels, total thiol content, HO-1, γ-glutamylcysteine synthetase, and p21 expression were evaluated. PCA induced, in a dose-dependent manner, a significantly reduced cell viability of CaCo-2 by oxidative/antioxidant imbalance. The phenolic acid induced modifications in levels of HO-1, non-proteic thiol groups, γ-glutamylcysteine synthetase, reactive oxygen species, and p21. PCA induced a pro-oxidant effect in cancer cells, and the in vitro pro-apoptotic effect on CaCo-2 cells is mediated by the modulation of redox balance and the inhibition of the HO-1 system that led to the activation of p21. Our results suggest that PCA may represent a useful tool in prevention and/or therapy of colon cancer.

11.
Trop Med Infect Dis ; 6(3)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34564545

RESUMO

Malaria still represents one of the most debilitating and deadly diseases in the world. It has been suggested that malaria has different impacts on women and men due to both social and biological factors. A gender perspective is therefore important to understand how to eliminate malaria. This study aimed to investigate malaria from a gender perspective in a non-for-profit private health facility, HopeXchange Medical Centre, based in Kumasi (Ghana). A sequential mixed-methods design, comprising quantitative and qualitative methods, was used. This study found low ownership (40%) and use (19%) of insecticide-treated nets (ITNs). Most malaria cases were women (62%), who were less educated and had more external risk factors associated with infection. Our study reported a trend of preferring malaria self-medication at home, which was practiced mostly by men (43%). Our data suggest that women are more likely to be exposed to malaria infections than men, especially due to their prolonged exposure to mosquito bites during the most dangerous hours. Our study highlighted the need for future malaria control policies to be more focused on social and behavioral aspects and from a gender perspective.

12.
Infection ; 49(6): 1241-1248, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34524648

RESUMO

PURPOSE: Since the first Italian case of SARS-CoV-2 was detected in Lombardy (Northern Italy)  Italy quickly became one of the worst-affected European countries, with a severe impact on health-care workers (HCWs). In the first epidemic, HCWs accounted for 12% of all national COVID-19 cases. We evaluated the burden of COVID-19 among HCWs and other non-health-care workers (nHCWs) in a large Italian hospital. METHODS: From March 1st to May 31st 2020, we performed a retrospective study at ASST Civil Hospital, in the Province of Brescia, Lombardy. The study population included all hospital personnel (n = 9265), categorized by professional status. RESULTS: A SARS-CoV-2 test was performed in 3572 workers (38.5%), with a positive result in 552 (5.9% of all hospital personnel). The temporal trend of SARS-CoV-2 cases in hospital staff broadly reflected that in the community, with a great majority of infections occurred during March 2020 (87.7%). From April onward, a steep decrease of positive cases was observed among hospital personnel, while in the community the decrease was much slower. Medical doctors (8.9%) and nurses (8.5%) were the most affected professional categories with a significantly higher risk of SARS-CoV-2 infection (OR 1.436 and OR 1.410, respectively p < 0.0001). HCWs in COVID-19 units presented a significantly higher risk of infection compared to HCWs in non-COVID units (p < 0.001). CONCLUSION: HCWs were severely affected by the COVID-19 epidemic, probably associated with an overwhelming burden of work and lack of preparedness in prevention of nosocomial transmission of the infection. The rapid decrease of COVID-19 spread in the hospital, registered before the one in the community, suggests that the adopted preventive measures were effective.


Assuntos
COVID-19 , Epidemias , Pessoal de Saúde , Hospitais , Humanos , Itália/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
13.
Nat Med ; 27(10): 1752-1760, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34480127

RESUMO

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/ß inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml-1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.


Assuntos
COVID-19/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Idoso , COVID-19/virologia , Método Duplo-Cego , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Masculino , Pessoa de Meia-Idade , Placebos , SARS-CoV-2/isolamento & purificação
14.
J Public Health Res ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558252

RESUMO

The emergence SARS-CoV-2 in late 2019 and early 2020 has caused a pandemic of unprecedented proportions. Management of COVID-19 became emergent public health priorities, and the impact on other public health initiatives, such as expanded HIV screening and linkage to care, remain largely unknown. In this Single-Center retrospective observational study, we describe the characteristics and circumstance of the new HIV cases during 2020 compared to 2019. We observed a decrease of HIV diagnosis during this period. Interestingly, median age at HIV diagnosis decreased of one decade and percentage of female patients was higher. In addition, more patients received diagnosis during hospitalization and more AIDS-defining conditions, such as Pneumocystis pneumonia, were detected. We express our concern that HIV new diagnoses will increase as a result of people's inability to get tested or treated in this period. More efforts are needed to improve local screening programs both during and after COVID-19 pandemic.

16.
Pharmaceutics ; 13(7)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34371719

RESUMO

Lipid nanoparticles (LNPs) have been proposed as carriers for drug skin delivery and targeting. As LNPs effectiveness could be increased by the addition of chemical penetration enhancers (PE), in this work, the feasibility of incorporating PE into LNPs to improve idebenone (IDE) targeting to the skin was investigated. LNPs loading IDE 0.7% w/w were prepared using hydrophilic (propylene glycol, PG, 10% w/w or N-methylpyrrolidone, NMP, 10% w/w) and/or lipophilic PE (oleic acid, OA, 1% w/w; isopropyl myristate, IPM, 3.5% w/w; a mixture of 0.5% w/w OA and 2.5% w/w IPM). All LNPs showed small sizes (<60 nm), low polydispersity index and good stability. According to the obtained results, IDE release from LNPs was not the rate-limiting step in IDE skin penetration. No IDE permeation was observed through excised pigskin from all LNPs, while the greatest increase of IDE penetration into the different skin layers was obtained using the mixture OA/IPM. The antioxidant activity of IDE-loaded LNPs, determined by the oxygen radical absorbance capacity assay, was greater than that of free IDE. These results suggest that the use of suitable PE as LNPs components could be regarded as a promising strategy to improve drug targeting to the skin.

17.
Trop Med Int Health ; 26(11): 1503-1511, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34455661

RESUMO

OBJECTIVE: To assess the state of the retention in care of HIV patients in three health settings in Morrumbene, a rural district of Inhambane Province, Mozambique. We evaluated potential factors associated with early loss to follow-up (LTFU), retention in care and ART adherence during the first year of follow-up. MATERIAL AND METHODS: Retrospective, cross-sectional, observational study. We collected data on patients diagnosed with HIV infection in 2017 in two permanent clinics and one mobile clinic. Demographic, clinical, immunological and therapeutic data were retrieved up to December 31st, 2018. Data on follow-up were collected at 6 and 12 months for medical visits and for ART adherence and analysed for factors associated with LTFU, retention in care and adherence to ART by Stata Version 14 and univariate and stepwise multiple unconditional logistic regression models. RESULTS: In 2017, 960 patients were diagnosed with HIV infection. At 6-month follow-up, 49% attended the medical visit and 157 (25%) adhered to ART. After one year, 34% of patients were available for follow-up, and only 72 patients adhered to ART. In multivariate analysis, factors associated with early LTFU were male sex (p = 0.036) and immediate prescription of ART (p = 0.064). Older age (p < 0.001) and being followed in the mobile clinic (p = 0.001) favoured retention in care. Advanced WHO status (p = 0.005) and being pregnant or breastfeeding showed a negative correlation with adherence to treatment (p = 0.068). CONCLUSIONS: Only one-third of patients were available for follow-up after one year, and only 13% adhered to ART. Young individuals, men and pregnant/breastfeeding women seem to be particularly at risk for LTFU and non-adherence to treatment.

18.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443491

RESUMO

Glycyrrhetic acid (GA) and stearyl glycyrrhetinate (SG) are two interesting compounds from Glycyrrhiza glabra, showing numerous biological properties widely applied in the pharmaceutical and cosmetic fields. Despite these appreciable benefits, their potential therapeutic properties are strongly compromised due to unfavourable physical-chemical features. The strategy exploited in the present work was to develop solid lipid nanoparticles (SLNs) as carrier systems for GA and SG delivery. Both formulations loaded with GA and SG (GA-SLNs and SG-SLNs, respectively) were prepared by the high shear homogenization coupled to ultrasound (HSH-US) method, and we obtained good technological parameters. DSC was used to evaluate their thermotropic behaviour and ability to act as carriers for GA and SG. The study was conducted by means of a biomembrane model (multilamellar vesicles; MLVs) that simulated the interaction of the carriers with the cellular membrane. Unloaded and loaded SLNs were incubated with the biomembranes, and their interactions were evaluated over time through variations in their calorimetric curves. The results of these studies indicated that GA and SG interact differently with MLVs and SLNs; the interactions of SG-SLNs and GA-SLNs with the biomembrane model showed different variations of the MLVs calorimetric curve and suggest the potential use of SLNs as delivery systems for GA.


Assuntos
Calorimetria , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacologia , Lipídeos/química , Nanopartículas/química , Ácido Glicirretínico/química , Cinética , Membranas , Eletricidade Estática , Temperatura de Transição
19.
Int J Mol Sci ; 22(13)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209673

RESUMO

A cytokine storm, autoimmune features and dysfunctions of myeloid cells significantly contribute to severe coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Genetic background of the host seems to be partly responsible for severe phenotype and genes related to innate immune response seem critical host determinants. The C9orf72 gene has a role in vesicular trafficking, autophagy regulation and lysosome functions, is highly expressed in myeloid cells and is involved in immune functions, regulating the lysosomal degradation of mediators of innate immunity. A large non-coding hexanucleotide repeat expansion (HRE) in this gene is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), both characterized by neuroinflammation and high systemic levels of proinflammatory cytokines, while HREs of intermediate length, although rare, are more frequent in autoimmune disorders. C9orf72 full mutation results in haploinsufficiency and intermediate HREs seem to modulate gene expression as well and impair autophagy. Herein, we sought to explore whether intermediate HREs in C9orf72 may be a risk factor for severe COVID-19. Although we found intermediate HREs in only a small portion of 240 patients with severe COVID-19 pneumonia, the magnitude of risk for requiring non-invasive or mechanical ventilation conferred by harboring intermediate repeats >10 units in at least one C9orf72 allele was more than twice respect to having shorter expansions, when adjusted for age (odds ratio (OR) 2.36; 95% confidence interval (CI) 1.04-5.37, p = 0.040). The association between intermediate repeats >10 units and more severe clinical outcome (p = 0.025) was also validated in an independent cohort of 201 SARS-CoV-2 infected patients. These data suggest that C9orf72 HREs >10 units may influence the pathogenic process driving more severe COVID-19 phenotypes.


Assuntos
Proteína C9orf72/genética , COVID-19/patologia , Repetições de Microssatélites , Adulto , Fatores Etários , Idoso , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/patologia , COVID-19/genética , COVID-19/virologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
20.
J Pers Med ; 11(6)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203982

RESUMO

The clinical presentation of COVID-19 is extremely heterogeneous, ranging from asymptomatic to severely ill patients. Thus, host genetic factors may be involved in determining disease presentation and progression. Given that carriers of single cystic fibrosis (CF)-causing variants of the CFTR gene-CF-carriers-are more susceptible to respiratory tract infections, our aim was to determine their likelihood of undergoing severe COVID-19. We implemented a cohort study of 874 individuals diagnosed with COVID-19, during the first pandemic wave in Italy. Whole exome sequencing was performed and validated CF-causing variants were identified. Forty subjects (16 females and 24 males) were found to be CF-carriers. Among mechanically ventilated patients, CF-carriers were more represented (8.7%) and they were significantly (p < 0.05) younger (mean age 51 years) compared to noncarriers (mean age 61.42 years). Furthermore, in the whole cohort, the age of male CF-carriers was lower, compared to noncarriers (p < 0.05). CF-carriers had a relative risk of presenting an abnormal inflammatory response (CRP ≥ 20 mg/dL) of 1.69 (p < 0.05) and their hazard ratio of death at day 14 was 3.10 (p < 0.05) in a multivariate regression model, adjusted for age, sex and comorbidities. In conclusion, CF-carriers are more susceptible to the severe form of COVID-19, showing also higher risk of 14-day death.

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