Long-term outcomes of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy and as switch strategy in virologically suppressed persons with HIV: data from the ICONA cohort.

OBJECTIVES: To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. METHODS: Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan-Meier curves and Cox regression models. RESULTS: Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19-2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53-3.82) higher risk; there were no differences in TF according to sex.Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. CONCLUSIONS: Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy.

B-cell-depleted patients with persistent SARS-CoV-2 infection: combination therapy or monotherapy? A real-world experience.

Objectives: The aim of the study was to describe a cohort of B-cell-depleted immunocompromised (IC) patients with prolonged or relapsing COVID-19 treated with monotherapy or combination therapy. Methods: This is a multicenter observational retrospective study conducted on IC patients consecutively hospitalized with a prolonged or relapsing SARS-CoV-2 infection from November 2020 to January 2023. IC COVID-19 subjects were stratified according to the monotherapy or combination anti-SARS-CoV-2 therapy received. Results: Eighty-eight patients were enrolled, 19 under monotherapy and 69 under combination therapy. The study population had a history of immunosuppression (median of 2 B-cells/mm3, IQR 1-24 cells), and residual hypogammaglobulinemia was observed in 55 patients. A reduced length of hospitalization and time to negative SARS-CoV-2 molecular nasopharyngeal swab (NPS) in the combination versus monotherapy group was observed. In the univariable and multivariable analyses, the percentage change in the rate of days to NPS negativity showed a significant reduction in patients receiving combination therapy compared to those receiving monotherapy. Conclusion: In IC persistent COVID-19 patients, it is essential to explore new therapeutic strategies such as combination multi-target therapy (antiviral or double antiviral plus antibody-based therapies) to avoid persistent viral shedding and/or severe SARS-CoV-2 infection.

Predictors of Mortality and Orotracheal Intubation in Patients with Pulmonary Barotrauma Due to COVID-19: An Italian Multicenter Observational Study during Two Years of the Pandemic.

Introduction: Coronavirus disease 2019 (COVID-19) is a significant and novel cause of acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, there has been an increase in the incidence of cases involving pneumothorax and pneumomediastinum. However, the risk factors associated with poor outcomes in these patients remain unclear. Methods: This observational study collected clinical and imaging data from COVID-19 patients with PTX and/or PNM across five tertiary hospitals in central Italy between 1 March 2020 and 1 March 2022. This study also calculated the incidence of PTX and PNM and utilized multivariable regression analysis and Kaplan-Meier curve analysis to identify predictor factors for 28-day mortality and 3-day orotracheal intubation after PTX/PNM. This study also considered the impact of the three main variants of concern (VoCs) (alfa, delta, and omicron) circulating during the study period. Results: During the study period, a total of 11,938 patients with COVID-19 were admitted. This study found several factors independently associated with a higher risk of death in COVID-19 patients within 28 days of pulmonary barotrauma. These factors included a SOFA score ≥ 4 (OR 3.22, p = 0.013), vasopressor/inotropic therapy (OR 11.8, p < 0.001), hypercapnia (OR 2.72, p = 0.021), PaO2/FiO2 ratio < 150 mmHg (OR 10.9, p < 0.001), and cardiovascular diseases (OR 7.9, p < 0.001). This study also found that a SOFA score ≥ 4 (OR 3.10, p = 0.015), PCO2 > 45 mmHg (OR 6.0, p = 0.003), and P/F ratio < 150 mmHg (OR 2.9, p < 0.042) were factors independently associated with a higher risk of orotracheal intubation (OTI) within 3 days from PTX/PNM in patients with non-invasive mechanical ventilation. SARS-CoV-2 VoCs were not associated with 28-day mortality or the risk of OTI. The estimated cumulative probability of OTI in patients after pneumothorax was 44.0% on the first day, 67.8% on the second day, and 68.9% on the third day, according to univariable survival analysis. In patients who had pneumomediastinum only, the estimated cumulative probability of OTI was 37.5%, 46.7%, and 57.7% on the first, second, and third days, respectively. The overall incidence of PTX/PNM among hospitalized COVID-19 patients was 1.42%, which increased up to 4.1% in patients receiving invasive mechanical ventilation. Conclusions: This study suggests that a high SOFA score (≥4), the need for vasopressor/inotropic therapy, hypercapnia, and PaO2/FiO2 ratio < 150 mmHg in COVID-19 patients with pulmonary barotrauma are associated with higher rates of intubation, ICU admission, and mortality. Identifying these risk factors early on can help healthcare providers anticipate and manage these patients more effectively and provide timely interventions with appropriate intensive care, ultimately improving their outcomes.

Risk of COVID-19 in-hospital mortality in people living with HIV compared to general population according to age and CD4 strata: data from the ICONA network.

OBJECTIVES: We aimed to study whether people living with HIV (PLWH) are at higher risk of in-hospital COVID-19 mortality compared to the general population (GenPop). METHODS: This was a retrospective study in 19 Italian centers (February 2020 to November 2022) including hospitalized PLWH and GenPop with SARS-CoV-2 infection. The main outcome was in-hospital mortality. Competing risk analyses by Fine-Gray regression model were used to estimate the association between in-hospital mortality and HIV status/age. RESULTS: A total of 7399 patients with COVID-19 were included, 239 (3.2%) PLWH, and 7160 (96.8%) GenPop. By day 40, in-hospital death occurred in 1283/7160 (17.9%) among GenPop and 34/239 (14.2%) among PLWH. After adjusting for potential confounders, compared to GenPop <65 years, a significantly higher risk of death was observed for GenPop ≥65 (adjusted subdistribution hazard ratio [aSHR] 1.79 [95% CI 1.39-2.31]), PLWH ≥65 (aSHR 2.16 [95% CI 1.15-4.04]), PLWH <65 with CD4 ≤200 (aSHR 9.69 [95% CI 5.50-17.07]) and PLWH <65 with CD4 201-350 (aSHR 4.37 [95% CI 1.79-10.63]), whereas no evidence for a difference for PLWH <65 with CD4 >350 (aSHR 1.11 [95% CI 0.41-2.99]). CONCLUSIONS: In PLWH aged <65 years a CD4 ≤350 rather than HIV itself seems the driver for the observed higher risk of in-hospital mortality. We cannot however rule out that HIV infection per se is the risk factor in those aged ≥65 years.

Unexpected effects of COVID-19 outbreak: adaption of Anti-Retroviral Therapy (ART) delivery policies improved adherence in a population of People Living With HIV (PLWH).

Background: Adherence to Anti-Retroviral Therapy (ART) is crucial for People Living With HIV (PLWH). In Italy, ART is delivered by Hospital Pharmacies, on a renewable prescription from the hospital physician. The measurement of package-refill (the rate of ART packages actually collected out of those to be collected in order to comply with therapy) is an effective tool to evaluate the adherence.During COVID-19 outbreak, at "D. Cotugno" hospital in Naples, Italy, the ART delivery policies have been adapted, in order to reduce the number of patients' access. We analysed the impact of these changes on the pill-refill of ART in January-August 2020, compared with 2018-2019. Methods: "D. Cotugno" hospital is a mono-specialistic Infectious Diseases hospital, caring for about 2500 PLWH. Since February 2020, the hospital was almost entirely dedicated to COVID-19 patients. All out-patient activities were interrupted, except for those dedicated to HIV/AIDS patients.In this preliminary study we included all patients assigned to one of the three Medical Divisions dedicated to HIV, who were already under treatment since at least 2017. Rate of package-refill was obtained by the Hospital Pharmacy registry, demographic and clinical data were derived from clinical database.During COVID-19, many measures were adopted in order to increase safety of PLWH attending to hospital. Among these, medical prescription validity increased from 4 to 6 months, and number of packages to be collected increased from 2 to 4, adopting a multi-month dispensing strategy.Package-refill is adequate if at least 95% of ART have been actually collected; partial and inadequate if 75%-94% or less than 75% of ART, respectively, have been collected. Package-refill was measured during the first year of COVID-19 (March 2020 - February 2021), compared to the same period in the two years before. Results: A total of 594 PLWH were included. PLWH with optimal pill-refill significantly increased in 2020-21 compared to 2018-2020 (62% vs 55%, p 0.013). Discussion: Due to COVID-19, we would have expected a reduction in ART deliveries. Surprisingly, the opposite occurred. The increase of pill-refill rates may be due to different reasons, but we hypothesized that the adaption of delivery policies, with a higher number of packages allowed to be collected, strongly contributed to this result. This study suggests that multi-month dispensing policies may contribute to the improvement of adherence among PLWH.

Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

Adherence to antiretroviral therapy thought package-refill among HIV+ persons at "D. Cotugno" hospital, Naples, Italy.

Background: A gold-standard for the measurement of adherence to antiretroviral therapy (ART) is lacking. Aim of this study is to verify the feasibility of a package-refill-based measurement of ART at "D. Cotugno" hospital, Naples, Italy, and the factors associated to adherence. Methods: In the period January 2018-August 2020, we calculated the package-refill as the ratio between ART-packages actually withdrawn, and the ART packages needed to regularly take ART. Adherence was associated, trough a univariate e multivariate logistic regression, to demographical, behavioural and clinical factors. Results: 1140 HIV+ subjects were included. At univariate logistic regression inadequate package-refill-based adherence is associated with HIV-RNA higher than 50 copies/mmL (OR 3.77-IC95% 2.76-5.13) and with HIVRNA higher than 200 copies/mmL (OR 3.98-IC95% 2.69-5.90). Being not-Italian and Injective-drug-user are associated with low adherence, having HIV/AIDS for more than 8 years is associated with better adherence. Conclusions: Package-refill is a suitable method for measuring adherence and is associated with the condition of viral failure.

Evolving epidemiology of HIV/AIDS in Campania region, 2011-2018: Is HIV/AIDS population in Campania different?

Objectives: Data on HIV/AIDS cases in Italy are collected using a standardised form. Regional epidemiology may vary. We described the epidemiological and clinical characteristics of newly diagnosed persons with HIV in the 'Cotugno' hospital in Naples during 2011-2018 and compared them with national data to identify similarities and differences. Methods: Data source for the Campania region is the data collection forms sent to the national surveillance system. The data source for the national data is from the periodic annual bulletins on HIV/AIDS published by the National Institute of Health. Results: In all, 1149 persons with HIV were diagnosed in 'Cotugno' (69.7% of those diagnosed in Campania). Persons with HIV in Campania showed many similarities with the Italian population: men were in the majority in both groups (about 75%), foreign origin was about 30%, heterosexuals were the most represented risk group, followed by men who have sex with men and injecting drug use in both samples. Some notable differences are also present. Among the risk factors for HIV acquisition, injecting drug use is significantly more common in Campania. Among the reasons for testing, significant differences are evident for almost all reasons, with screening activities (testing for concurrent diseases, for diagnosis of sexually transmitted diseases, screening in hospital during maternity care and screening in drug-addition services or prisons) being more common at the national level. The Campania population has a more severe disease pattern, with a significantly higher proportion of patients diagnosed with less than 200 CD4 cells/µL and AIDS. For each variable, we compared trends in the Campania region and in Italy using Spearman's correlation coefficient. Almost all trends show a weak correlation. Conclusion: In conclusion, the prevalence of injecting drug use is still consistent, and requires specific campaigns. The reasons for testing are different: screening activities work less in Campania than in Italy. This untimely approach contributes to a more severe clinical picture in Campania.

Epidemiology of HCV and HBV in a High Endemic Area of Southern Italy: Opportunities from the COVID-19 Pandemic-Standardized National Screening or One Tailored to Local Epidemiology?

The COVID-19 pandemic led to the hospitalization of an unselected population with the possibility to evaluate the epidemiology of viral hepatitis. Thus, a retrospective multicenter study was conducted in an area of Southern Italy with the aim of assessing the prevalence of HCV and HBV markers and the ability of current screening program to capture cases. We evaluated 2126 hospitalized patients in seven COVID Centers of Naples and Caserta area in which 70% of the Campania population lives. HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively, with no differences between gender. Decade distribution for birth year shows a bimodal trend of HCV prevalence, with a peak (11.6%) in the decade 1930-1939 and a second peak (5.6%) for those born in 1960-1969. An analysis of the screening period imposed by the Italian government for those born between 1969 and 1989 shows that only 17% of cases of HCV infection could be captured. A small alignment of the screening period, i.e., those born from 1960 to 1984, would capture 40% of cases. The data confirm the high endemicity of our geographical area for hepatitis virus infections and underline the need for a tailored screening program according to the regional epidemiology.

Parietal intrahemispheric source connectivity of resting-state electroencephalographic alpha rhythms is abnormal in Naïve HIV patients.

Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4 Hz) and alpha (8-12 Hz) rhythms in treatment-Naïve HIV (Naïve HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder. The present EEG database regarded 128 Naïve HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals. Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naïve HIV than in the control group. Furthermore, those abnormalities were greater in the Naïve HIV subgroup with executive and visuospatial deficits than the Naïve HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75-0.88) in the discrimination between the Naïve HIV individuals with executive and visuospatial deficits vs. Naïve HIV individuals with normal cognition and control individuals. In quiet wakefulness, Naïve HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal "hub" oscillating at the alpha frequency in quiet wakefulness as a brain network disorder.

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism.

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Dysregulation of lipid metabolism and pathological inflammation in patients with COVID-19.

In recent months, Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. COVID-19 patients show mild, moderate or severe symptoms with the latter ones requiring access to specialized intensive care. SARS-CoV-2 infections, pathogenesis and progression have not been clearly elucidated yet, thus forcing the development of many complementary approaches to identify candidate cellular pathways involved in disease progression. Host lipids play a critical role in the virus life, being the double-membrane vesicles a key factor in coronavirus replication. Moreover, lipid biogenesis pathways affect receptor-mediated virus entry at the endosomal cell surface and modulate virus propagation. In this study, targeted lipidomic analysis coupled with proinflammatory cytokines and alarmins measurement were carried out in serum of COVID-19 patients characterized by different severity degree. Serum IL-26, a cytokine involved in IL-17 pathway, TSLP and adiponectin were measured and correlated to lipid COVID-19 patient profiles. These results could be important for the classification of the COVID-19 disease and the identification of therapeutic targets.

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study.

INTRODUCTION: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. METHODS: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. CONCLUSION: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry.

BACKGROUND: Currently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population. METHODS: This was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death. RESULTS: Among 148 PWH followed for a median (interquartile range) of 47 (32-84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85-11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%-13%), and that of ≥1 event or death was 22% (95% CI, 16%-31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07-6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65-1.02). CONCLUSIONS: PWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

Use of lung ultrasound in COVID-19: comparison with ultra-high-resolution computed tomography among 29 patients at "D. Cotugno" hospital, Naples, Italy.

Ultra-High-Resolution Computed Tomography (U-HR-CT) is the reference imaging technique for pneumonia in the new coronavirus disease (COVID-19). Pulmonary Ultrasound (LUS) could be a valid diagnostic alternative for the imaging of COVID-19. Our study aimed to investigate the clinical performance of LUS in the initial evaluation of pneumonia in COVID-19 patients, compared to standard U-HR-CT. Among 29 patients with confirmed COVID-19, all U-HR-CT hallmarks showed an excellent concordance with LUS findings according to Cohen coefficient. In our experience, LUS is a viable alternative to U-HR-CT, with the advantages of being radiation-free, flexible, cost-effective, and reasonably reducing nosocomial transmission risks because performed at bed-side.

Differences among confirmed and not-confirmed COVID-19 patients at "D.Cotugno" hospital, Naples (Italy): what we learned from first suspected cases?

Clinical presentation of COVID-19 is common to other respiratory infections. We compared the characteristics at hospital admission of confirmed and not-confirmed COVID-19 patients, in the early phase of the epidemic. Thirty-seven suspected patients were enrolled, and COVID-19 was confirmed in 17. Confirmed patients are older, have more frequently contact with confirmed cases. Distinctive clinical characteristics among COVID-19 were the grand-glass opacities at CT scan, and a pO2/FiO2 ratio less than 250. In not-confirmed group, Influenza represented the most frequent alternative diagnosis. This study contributes to highlight the characteristics to consider at hospital admission in order to promptly suspect COVID-19.

Fever of unknown origin (FUO): which are the factors influencing the final diagnosis? A 2005-2015 systematic review.

BACKGROUND: The differential diagnosis of Fever of Unknown Origin (FUO) is very extensive, and includes infectious diseases (ID), neoplasms and noninfectious inflammatory diseases (NIID). Many FUO remain undiagnosed. Factors influencing the final diagnosis of FUO are unclear. METHODS: To identify factors associated with FUO diagnostic categories, we performed a systematic review of classical FUO case-series published in 2005-2015 and including patients from 2000. Moreover, to explore changing over time, we compared these case-series with those published in 1995-2004. RESULTS: Eighteen case-series, including 3164 patients, were included. ID were diagnosed in 37.8% of patients, NIID in 20.9%, and neoplasm in 11.6%, FUO were undiagnosed in 23.2%. NIIDs significantly increased over time. An association exists between study country income level and ID (increasing when the income decreases) and undiagnosed FUO (increasing when the income increases); even if not significant, the use of a pre-defined Minimal Diagnostic Work-up to qualify a fever as FUO seems to correlate with a lower prevalence of infections and a higher prevalence of undiagnosed FUO. The multivariate regression analysis shows significant association between geographic area, with ID being more frequent in Asia and Europe having the higher prevalence of undiagnosed FUO. Significant associations were found with model of study and FUO defining criteria, also. CONCLUSIONS: Despite advances in diagnostics, FUO still remains a challenge, with ID still representing the first cause. The main factors influencing the diagnostic categories are the income and the geographic position of the study country.