Epidemiology of Strongyloides stercoralis in northern Italy: Results of a multicentre case-control study, February 2013 to July 2014

Strongyloides stercoralis is a soil-transmitted helminth widely diffused in tropical and subtropical regions of the world. Autochthonous cases have been also diagnosed sporadically in areas of temperate climate. We aimed at defining the epidemiology of strongyloidiasis in immigrants and Italians living in three northern Italian Regions. Screening for S. stercoralis infection was done with serology, confirmation tests were a second serological method or stool agar culture. A case-control approach was adopted and patients with a peripheral eosinophil count 65 500/mcL were classified as cases. Of 2,701 individuals enrolled here 1,351 were cases and 1,350 controls; 86% were Italians, 48% women. Italians testing positive were in 8% (97/1,137) cases and 1% (13/1,178) controls (adjusted odds ratio (aOR) 8.2; 95% confidence interval (CI): 4.5-14.8), while positive immigrants were in 17% (36/214) cases and in 2% (3/172) controls (aOR 9.6; 95% CI: 2.9-32.4). Factors associated with a higher risk of infection for all study participants were eosinophilia (p < 0.001) and immigration (p = 0.001). Overall, strongyloidiasis was nine-times more frequent in individuals with eosinophilia than in those with normal eosinophil count

Community-acquired Klebsiella pneumoniae meningitis in an alcoholic patient with an infected pancreatic pseudocyst; a case report and review of literature

We report a case of a 49-year-old male with a history of chronic alcoholism and evidence of a pancreatic pseudocyst on CT scanning. He presented with a 3-days history of fever, loss of appetite and upper abdominal pain. Blood cultures grew Klebsiella pneumoniae and he improved clinically with a seven-day course of intravenous co-amoxiclav and metronidazole. Two weeks later he was readmitted to hospital with impaired consciousness and septic shock, and died three days later in intensive care. Post mortem examination revealed bacterial meningitis and an infected pancreatic pseudocyst. Klebsiella pneumoniae was isolated from the pancreas and meninges

Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized. Methods: A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases. Results: Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis. Conclusion: RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk. Trial Registration NCT04549831 (www.clinicaltrial.org

Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

The 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 ((Formula presented.) and (Formula presented.)). By applying a logistic regression with both IPGS, ((Formula presented.) (or indifferently (Formula presented.)) 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%

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10−8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10−8). A total of 113 variants were associated with survival at P-value < 1.0 × 10−5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

Cerebrospinal fluid penetration of levofloxacin in patients with spontaneous acute bacterial meningitis

We have assessed levofloxacin penetration in cerebrospinal fluid (CSF) and the liquor-to-plasma ratio (C(L)/C(P)) at 2 hours after dosing in 5 patients with spontaneous acute bacterial meningitis. CSF levofloxacin concentration at 2 hours after dosing was 1.99+/-0.67 microg/mL, and the C(L)/C(P) at 2 hours after dosing was 0.34+/-0.09

Comparison between dexamethasone and methylprednisolone therapy in patients with COVID-19 pneumonia admitted to non-intensive medical units

(1) Background: Data on different steroid compounds for the treatment of hospitalized COVID-19 (coronavirus disease 2019) patients are still limited. The aim of this study was to compare COVID-19 patients admitted to non-intensive units and treated with methylprednisolone or dexamethasone. (2) Methods: This was a single-center retrospective study that included consecutive patients with COVID-19 hospitalized in medical wards during the second wave of the pandemic. Thirty-day mortality and the need for intensive or semi-intensive care were the main clinical outcomes analyzed in patients receiving methylprednisolone (60 mg/day) compared with dexamethasone (6 mg/day). Secondary outcomes included complication rates, length of hospital stay, and time to viral clearance. (3) Results: Two-hundred-forty-six patients were included in the analysis, 110 treated with dexamethasone and 136 with methylprednisolone. No statistically significant differences were found between the two groups of patients regarding 30-day mortality (OR 1.35, CI95% 0.71–2.56, p = 0.351) and the need for intensive or semi-intensive care (OR 1.94, CI95% 0.81–4.66, p = 0.136). The complication rates, length of hospital stay, and time to viral clearance did not significantly differ between the two groups. (4) Conclusions: In patients hospitalized for COVID-19 in non-intensive units, the choice of different steroid compounds, such as dexamethasone or methylprednisolone, did not affect the main clinical outcomes