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SARS-CoV-2 infection is characterized by several clinical manifestations, ranging from the absence of symptoms to severe forms that necessitate intensive care treatment. It is known that the patients with the highest rate of mortality develop increased levels of proinflammatory cytokines, called the "cytokine storm", which is similar to inflammatory processes that occur in cancer. Additionally, SARS-CoV-2 infection induces modifications in host metabolism leading to metabolic reprogramming, which is closely linked to metabolic changes in cancer. A better understanding of the correlation between perturbed metabolism and inflammatory responses is necessary. We evaluated untargeted plasma metabolomics and cytokine profiling via 1H-NMR (proton nuclear magnetic resonance) and multiplex Luminex assay, respectively, in a training set of a limited number of patients with severe SARS-CoV-2 infection classified on the basis of their outcome. Univariate analysis and Kaplan-Meier curves related to hospitalization time showed that lower levels of several metabolites and cytokines/growth factors, correlated with a good outcome in these patients and these data were confirmed in a validation set of patients with similar characteristics. However, after the multivariate analysis, only the growth factor HGF, lactate and phenylalanine retained a significant prediction of survival. Finally, the combined analysis of lactate and phenylalanine levels correctly predicted the outcome of 83.3% of patients in both the training and the validation set. We highlighted that the cytokines and metabolites involved in COVID-19 patients' poor outcomes are similar to those responsible for cancer development and progression, suggesting the possibility of targeting them by repurposing anticancer drugs as a therapeutic strategy against severe SARS-CoV-2 infection.
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COVID-19 , Neoplasias , Humanos , SARS-CoV-2 , Citocinas , LactatosRESUMO
The evolution and the development of the symptoms of Coronavirus disease 19 (COVID-19) are due to different factors, where the microbiome plays a relevant role. The possible relationships between the gut, lung, nasopharyngeal, and oral microbiome with COVID-19 have been investigated. We analyzed the nasal microbiome of both positive and negative SARS-CoV-2 individuals, showing differences in terms of bacterial composition in this niche of respiratory tract. The microbiota solution A (Arrow Diagnostics) was used to cover the hypervariable V1-V3 regions of the bacterial 16S rRNA gene. MicrobAT Suite and MicrobiomeAnalyst program were used to identify the operational taxonomic units (OTUs) and to perform the statistical analysis, respectively. The main taxa identified in nasal microbiome of COVID-19 patients and in Healthy Control subjects belonged to three distinct phyla: Proteobacteria (HC = 14%, Cov19 = 35.8%), Firmicutes (HC = 28.8%, Cov19 = 30.6%), and Actinobacteria (HC = 56.7%, Cov19 = 14.4%) with a relative abundance > 1% in all groups. A significant reduction of Actinobacteria in Cov19 group compared to controls (P < 0.001, FDR = 0.01) was found. The significant reduction of Actinobacteria was identified in all taxonomic levels down to the genus (P < 0.01) using the ANOVA test. Indeed, a significantly reduced relative abundance of Corynebacterium was found in the patients compared to healthy controls (P = 0.001). Reduced abundance of Corynebacterium has been widely associated with anosmia, a common symptom of COVID-19 as suffered from our patients. Contrastingly, the Corynebacterium genus was highly represented in the nasal mucosa of healthy subjects. Further investigations on larger cohorts are necessary to establish functional relationships between nasal microbiota content and clinical features of COVID-19.
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Actinobacteria , COVID-19 , Microbiota , Humanos , Anosmia , RNA Ribossômico 16S/genética , SARS-CoV-2/genética , Bactérias/genética , Corynebacterium/genética , Actinobacteria/genéticaRESUMO
The neuromuscular patients may experience the need for respiratory support due to the onset of respiratory failure. Some skills are essential to achieve therapeutic success. In addition to technical knowledge, it is essential to have knowledge relating to individual neuromuscular diseases. The availability of alternative respiratory supports and various interfaces can be a valuable weapon at different moments in the course of the neuromuscular disease. Furthermore, the doctor-patient relationship plays a key role as does taking care of the patient's psychological sphere.
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Doenças Neuromusculares , Ventilação não Invasiva , Insuficiência Respiratória , Humanos , Doenças Neuromusculares/terapia , Ventilação não Invasiva/métodos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/etiologiaRESUMO
(1) Background: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV1 decline than the PI*MS group (p = 0.04 and p = 0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p = 0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV1, FEV1/FVC and DLCO (p = 0.0004, p < 0.0001, p = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV1 and DLCO decline (p = 0.0022, p = 0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV1, FEV1/FVC and DLCO annual decline in comparison with healthy PI*MR (p = 0.0083, p = 0.043, p = 0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.
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Congenital myopathies (CMs) are a clinically and genetically heterogeneous group of disorders characterized by early onset weakness, hypotonia and characteristic structural abnormalities in muscle fibres. Hypotonia and weakness can be present at birth or appear in infancy, and a static or slowly progressive clinical course may present with muscle weakness, loss of spontaneous movement, involuntary muscle activity, and muscle atrophy. Often patients develop a restrictive syndrome and respiratory failure and require respiratory support In our case, we described lung improvement and respiratory muscle training due to singing in a young patient, affected by CMs with a poor adherence to non-invasive mechanical ventilation.
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Miopatias Congênitas Estruturais , Canto , Recém-Nascido , Humanos , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/terapia , Hipotonia Muscular , Fibras Musculares Esqueléticas , PulmãoRESUMO
COVID-19 encompasses a broad spectrum of clinical conditions caused by SARS-CoV-2 infection. More severe cases experience acute respiratory and/or multiorgan failure. KL-6 is a glycoprotein expressed mainly from type II alveolar cells with pro-fibrotic properties. Serum KL-6 concentrations have been found in patients with COVID-19. However, the relevance of KL-6 in patients with severe and critical COVID-19 has not been fully elucidated. Methods: Retrospective data from consecutive severe to critical COVID-19 patients were collected at UOC Clinica Pnuemologica "Vanvitelli", A.O. dei Colli, Naples, Italy. The study included patients with a positive rhinopharyngeal swab for SARS-CoV-2 RNA with severe or critical COVID-19. Results: Among 87 patients, 24 had poor outcomes. The median KL-6 value in survivors was significantly lower when compared with dead or intubated patients (530 U/mL versus 1069 U/mL p < 0.001). KL-6 was correlated with body mass index (BMI) (r: 0.279, p: 0.009), lung ultrasound score (LUS) (r: 0.429, p < 0.001), Chung Score (r: 0.390, p < 0.001). KL-6 was associated with the risk of death or oro-tracheal intubation (IOT) after adjusting for gender, BMI, Charlson Index, Chung Score, and PaO2/FIO2 (OR 1.003 95% CI 1.001−1.004, p < 0.001). Serum KL-6 value of 968 has a sensitivity of 79.2%, specificity of 87.1%, PPV 70.4%, NPV 91.5%, AUC: O.85 for risk of death or IOT. Conclusions: The presented research highlights the relevance of serum KL-6 in severe to critical COVID-19 patients in predicting the risk of death or IOT.
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The vaccination campaign and the new SARS-CoV-2 variants may have changed the clinical profile and outcomes of patients admitted to sub-intensive unit care. We conducted a retrospective study aimed to compare the clinical and radiological features of unvaccinated critical COVID-19 patients hospitalized during the last pandemic wave (December 2021−February 2022, No-Vax group) and before starting the vaccination campaign (March−December 2020, Pre-Vax group). The No-Vax group was also compared with vaccinated patients of the same pandemic wave (Vax group). With respect to the Pre-Vax group, the No-Vax group contained a higher percentage of smokers (p = 0.0007) and a lower prevalence of males (p = 0.0003). At admission, the No-Vax patients showed both a higher CT score of pneumonia and a worse severe respiratory failure (p < 0.0001). In the No-Vax group, a higher percentage of deaths occurred, though this was not significant. In comparison with the No-Vax group, the Vax patients were older (p = 0.0097), with a higher Charlson comorbidity index (p < 0.0001) and a significantly lower HRCT score (p = 0.0015). The percentage of deaths was not different between the two groups. The No-Vax patients showed a more severe disease in comparison with the Pre-Vax patients, and were younger and had fewer comorbidities than the Vax patients.
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The aim of this study was to investigate the epidemiology of kidney replacement treatment (KRT) in Italy with a focus on gender and residence. As a population-based study using administrative databases from the Campania region of Italy between 2015 and 2018, the study outcomes included diagnoses of haemodialysis, peritoneal dialysis, kidney transplant, and mortality. A total of 11,713 residents in Campania were on KRT from 2015 to 2018. The annual prevalence ranged between 1000 and 1015 patients per million population (pmp) for haemodialysis, between 115 and 133 pmp for peritoneal dialysis, and between 2081 and 2245 pmp for kidney transplant. The annual incidence ranged between 160 and 185 pmp for de novo haemodialysis and between 59 and 191 pmp for kidney transplant. Annual mortality ranged between 12.8% and 14.2% in haemodialysis, between 5.2% and 13.8% in peritoneal dialysis, and between 2.4% and 3.3% in kidney transplant. In Cox regression targeting mortality, significant HRs were found for age (95%CI = 1.05/1.05), kidney transplant (compared to haemodialysis: 0.37/0.47), residence in suburban areas (1.03/1.24), and de novo dialysis incidence in years 2015-2018 (1.01/1.17). The annual rate of kidney transplant was 2.6%. In regression targeting kidney transplant rate, significant HRs were found for female gender (0.67/0.92), age (0.93/0.94), residence in suburban areas (0.65/0.98), and de novo incidence of dialysis in 2015-2018 (0.49/0.71). The existence of socioeconomic inequities in KRT is suggested by the evidence that gender and suburban residence predicted mortality and/or access to kidney transplant.
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KL-6 is a sialoglycoprotein antigen which proved elevated in the serum of patients with different interstitial lung diseases, especially in those with a poorer outcome. Given that interstitial pneumonia is the most common presentation of SARS-CoV2 infection, we evaluated the prognostic role of KL-6 in patients with COVID-19 pneumonia. Patients with COVID-19 pneumonia were prospectively enrolled. Blood samples were collected at the time of enrolment (TOE) and on day 7 (T1). Serum KL-6 concentrations were measured by chemiluminescence enzyme immunoassay using a KL-6 antibody kit (LUMIPULSE G1200, Fujirebio) and the cut-off value was set at >1000 U/mL. Fifteen out of 34 enrolled patients (44.1%) died. Patients with unfavourable outcome showed significantly lower P/F ratio and higher IL-6 values and plasmatic concentrations of KL-6 at TOE compared with those who survived (median KL-6: 1188 U/mL vs. 260 U/mL, p < 0.001). KL-6 > 1000 U/mL resulted independently associated with death (aOR: 11.29, p < 0.05) with a positive predictive value of 83.3%. Our results suggest that KL-6 is a reliable indicator of pulmonary function and unfavourable outcome in patients with COVID-19 pneumonia. A KL-6 value > 1000 U/mL resulted independently associated with death and showed good accuracy in predicting a poorer outcome. KL-6 may thus represent a quick, inexpensive, and sensitive parameter to stratify the risk of severe respiratory failure and death.
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COVID-19/diagnóstico , Mucina-1/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background: real-world data on COVID-19 vaccine safety, immunogenicity and acceptance in adults with congenital heart disease (ACHD) are lacking. Methods: ACHD patients who were offered COVID-19 vaccination from January to June 2021 were included. Data on adverse events, on patients' attitude towards vaccination and antispike IgG titre were retrospectively collected. A group of healthy individuals with similar age and sex undergoing vaccination was included for comparison. Results: 208 patients followed in a single ACHD tertiary centre (33.3 [26-45] years, 54% male) received COVID-19 vaccine, 65% vaccinated at our institution: 199 (96%) received Pfizer-BioNTech BNT162b2 vaccine, 4 (2%) Moderna-1273 and 5 (2%) AstraZeneca-ChAdOx1. Median follow-up after vaccination was 79 [57-96] days. No major adverse event was reported and the incidence of minor events was not different between ACHD patients and the control group. One patient was diagnosed with acute pericarditis. There were two deaths unrelated to the vaccine during follow-up. Three (1.5%) vaccinated patients tested positive for COVID-19. Antispike IgG titre, available in 159 (76%) patients, was 1334 [600-3401] BAU/ml, not significantly different from the control group (p=0.2). One patient with Fontan failure was seronegative. Advanced physiological stage was associated with lower antibody response, independently from previous viral exposure (p<0.0001). Fourteen percent refused COVID-19 vaccination at our institution. However, 50% of vaccinated patients declared to have been influenced by the discussion with the ACHD cardiologist and 66% of those vaccinated in situ reported that undergoing COVID-19 vaccination at the ACHD centre made them feel safer. Conclusion: COVID-19 vaccines appear safe in ACHD with satisfactory immunogenicity. However, the most vulnerable patients showed lower antibody response. ACHD team may play a key role in vaccine acceptance.
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In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.