103 research outputs found
Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features
No full textThe impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147-173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%-60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into "Boolean quantum features," inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores ( IPGS p h 1 and IPGS p h 2 ). By applying a logistic regression with both IPGS, ( IPGS p h 2 (or indifferently IPGS p h 1 ) and age as inputs, we reached an accuracy of 84%-86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147-173) by a factor of 10%
The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males
No full textThe polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways
Severe COVID-19 in Hospitalized Carriers of Single CFTR Pathogenic Variants
No full textThe 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
Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19
No full textThrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF–platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage
Long COVID in pediatric age: an observational, prospective, longitudinal, multicenter study in Italy
No full textIntroduction: This observational prospective longitudinal multicenter study examines the occurrence and characteristics of long COVID (LC) in the Italian pediatric population. Methods: Conducted across 12 Pediatric Units in Italy from January to March 2022, the study involved 1129 children diagnosed with SARS-CoV-2 infection. Data were collected via self-administered questionnaires at 1-3 months, 3-6 months, and 6-12 months post-infection, with LC defined as symptoms persisting for at least 2 months and occurring 3 months post-diagnosis. Results: Results revealed that 68.6% of children reported at least one post-COVID symptom, with 16.2% experiencing LC. The most frequent symptoms included respiratory issues (43.4%), neurological and cognitive dysfunction (27.7%), gastrointestinal symptoms (22.1%), fatigue (21.6%), and sleep disturbances (18.8%). Age and gender differences were significant, with older children and females more prone to cardiovascular and neurological & cognitive dysfunction. Discussion: The study highlights that LC in children presents similarly to adults, though less frequently. The occurrence of LC was lower compared to adult populations, likely due to the generally milder course of COVID-19 in children. The findings underscore the need for targeted follow-up and support for affected children, especially considering the long-term persistence of symptoms. Further research is necessary to explore the impact of COVID-19 vaccines on pediatric LC and the effects of different SARS-CoV-2 variants. These insights are crucial for developing strategies to manage and mitigate long-term impacts in children recovering from COVID-19
Impact of COVID-19 on vascular patients worldwide: analysis of the COVIDSurg data
No full textBACKGROUND: The COVIDSurg collaborative was an international multicenter prospective analysis of perioperative data from 235 hospitals in 24 countries. It found that perioperative COVID-19 infection was associated with a mortality rate of 24%. At the same time, the COVER study demonstrated similarly high perioperative mortality rates in vascular surgical patients undergoing vascular interventions even without COVID-19, likely associated with the high burden of comorbidity associated with vascular patients. This is a vascular subgroup analysis of the COVIDSurg cohort. METHODS: All patients with a suspected or confirmed diagnosis of COVID-19 in the 7 days prior to, or in the 30 days following a vascular procedure were included. The primary outcome was 30-day mortality. Secondary outcomes were pulmonary complications (adult respiratory distress syndrome, pulmonary embolism, pneumonia and respiratory failure). Logistic regression was undertaken for dichotomous outcomes. RESULTS: Overall, 602 patients were included in this subgroup analysis, of which 88.4% were emergencies. The most common operations performed were for vascular-related dialysis access procedures (20.1%, N.=121). The combined 30-day mortality rate was 27.2%. Composite secondary pulmonary outcomes occurred in half of the vascular patients (N.=275, 45.7%). CONCLUSIONS: Mortality following vascular surgery in COVID positive patients was significantly higher than levels reported pre-pandemic, and similar to that seen in other specialties in the COVIDSurg cohort. Initiatives and surgical pathways that ensure vascular patients are protected from exposure to COVID-19 in the peri-operative period are vital to protect against excess mortality. (Cite this article as: Hitchman L, Machin M; The COVIDSurg Collaborative and Vascular and Endovascular Research Network. Impact of COVID-19 on vascular patients worldwide: analysis of the COVIDSurg data. J Cardiovasc Surg 2021;62:558-70. DOI: 10.23736/S0021-9509.21.12024-5
Outcomes of COVID-19 Patients with Severe Hypoxemic Acute Respiratory Failure: Non-Invasive Ventilation vs. Straight Intubation—A Propensity Score-Matched Multicenter Cohort Study
No full textThe best timing for endotracheal intubation in patients with coronavirus disease 2019 (COVID-19) hypoxemic acute respiratory failure (hARF) remains debated. Aim of this study is to compare the outcomes of COVID-19 patients with hARF receiving either a trial of non-invasive ventilation (NIV) or intubated with no prior attempt of NIV (“straight intubation”). All consecutive patients admitted to the 25 participating ICUs were included and divided in two groups: the “straight intubation” group and the “NIV” group. A propensity score matching was performed to correct for biases associated with the choice of the respiratory support. Primary outcome was in-hospital mortality. Secondary outcomes were length of mechanical ventilation, hospital stay and reintubation rate. A total of 704 COVID-19 patients were admitted to ICUs during the study period. After matching, 141 patients were included in each group. No clinically relevant difference at ICU admission was found between groups. In-hospital mortality was significantly lower in the NIV group (22.0% vs. 36.2%), with no significant difference in secondary endpoints. There was no significant mortality difference between patients who received straight intubation and those intubated after NIV failure. In COVID-19 patients with hARF it is worth and safe attempting a trial of NIV prior to intubation
Use of Remdesivir in children with COVID-19: report of an Italian multicenter study
No full textBackground: COVID-19 is generally milder in children than in adults, however severe infection has been described in some patients. Few data are available on use of Remdesivir (RDV) in children, as most clinical trials focused on adult patients. We report a multicenter study conducted in 10 Italian Hospitals to investigate the safety of RDV in children affected by COVID-19. Methods: We collected the clinical data of children with COVID-19 treated with RDV between March 2020 and February 2022 in 10 Italian hospitals. Clinical data were compared according to a duration of RDV therapy more or less than 5 days. Linear regression model was used to determine the association of significant variables from the bivariate analysis to the duration of RDV therapy. Results: A total of 50 patients were included, with a median age of 12.8 years. Many patients had at least one comorbidity (78%), mostly obesity. Symptoms were fever (88%), cough (74%) and dyspnea (68%). Most patients were diagnosed with pneumonia of either viral and/or bacterial etiology. Blood test showed leukopenia in 66% and increased C-reactive protein (CRP) levels in 63% of cases. Thirty-six patients received RDV for 5 days, nine patients up to 10 days. Most children who received RDV longer were admitted to the PICU (67%). Treatment with RDV was well tolerated with rare side effects: bradycardia was recorded in 6% of cases, solved in less than 24 h after discontinuation. A mild elevation of transaminases was observed in 26% of cases, however for the 8%, it was still detected before the RDV administration. Therefore, in these cases, we could not establish if it was caused by COVID-19, RDV o both. Patients who received RDV for more than 5 days waited longer for its administration after pneumonia diagnosis. The presence of comorbidities and the duration of O2 administration significantly correlated with the duration of RDV therapy at the linear regression analysis. Conclusion: Our experience indicates that RDV against SARS-CoV-2 is safe and well-tolerated in pediatric populations at high risk of developing severe COVID-19. Our data suggest that delaying RDV therapy after diagnosis of pneumonia may be associated with a longer duration of antiviral therapy, especially in patients with comorbidities
Alpha-Lipoic Acid for the Prevention of Diabetic Macular Edema
No full textIntroduction: To evaluate the effect of alpha-lipoic acid (ALA) on the occurrence of diabetic macular edema. Methods: Randomized, double-blind, placebo-controlled, multicenter, multinational study. Patients were randomized to the treatment group with 600 mg ALA per day or the placebo group. Every 6 months stereo fundus photographs, HbA1c levels, and an ophthalmological examination were documented. The primary endpoint was the occurrence of clinically significant macular edema (CSME) within a follow-up period of 2 years. Results: We randomized 235 patients with type II diabetes mellitus into the treatment group (mean age 58.0 years) and 232 into the placebo group (mean age 57.9 years). Mean HbA1c level was 8.1, with no significant differences between the treatment (mean 8.2, SD +/- 1.35) and placebo groups (mean 8.1, SD +/- 1.29). HbA1c values remained constant over time. In the treatment and placebo groups, 84 and 86 patients (35.7 and 37.1%) had insulin-dependent diabetes mellitus (IDDM) with a median duration of diabetes of 9.3 versus 9.0 years in the placebo group. Visual acuity remained unchanged during the entire trial. Concerning the primary endpoint, the study provided a negative result, i.e. 26/235 patients in the treatment group and 30/232 patients in the placebo group developed CSME. Confirmatory intention-to-treat analysis of the primary endpoint revealed no statistically significant difference between groups (log-rank test, p = 0.7108, HR = 0.9057 with CI = 0.5355-1.5317). Median follow-up was identical (2.00 years). Conclusions: A daily dosage of 600 mg ALA does not prevent the occurrence of CSME in IDDM patients. Copyright (C) 2011 S. Karger AG, Base
Steroid in the treatment of outpatient COVID-19: A multicenter randomized controlled trial
No full textBackground: Early treatment of COVID-19 patients could reduce hospitalization and death. The effect of corticosteroids in the outpatient setting is still unknown. This study aimed to determine the effect of corticosteroids in the prevention of hospitalization of nonsevere cases.
Materials and Methods: This study is a multicenter randomized controlled trial. Seventy five nonsevere COVID-19 patients presented between days 7 and 14 of their symptoms received either prednisolone or placebo. The primary outcome was hospitalization. The study protocol was registered in the Iranian Registry of Clinical Trials on December 2, 2020 (IRCT20171219037964N2).
Results: Although the rate of hospitalization in the prednisolone group was higher than the placebo group (10.8% vs. 7.9%, respectively), it was not statistically significant (P value.,6). One patient in each group reported an adverse event and withdrew the medication.
Conclusion: Considering the null effect of corticosteroids in the prevention of hospitalization in outpatient settings, it is suggested not to consider corticosteroids for outpatient treatment
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