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Research into effective predictive markers and therapeutic interventions for COVID-19 remains of considerable interest. Vitamin D may be relevant, especially in frail populations in whom deficiency is more prevalent. In this prospective observational cohort study, 139 patients with moderate-to-severe COVID-19 who were hospitalized during the third wave of the pandemic in Italy were enrolled. Plasma vitamin D concentrations (both 25-hydroxyvitamin D-25(OH)D and 1,25-dihydroxyvitamin D-1,25(OH)2D) together with parathyroid hormone levels were measured using a chemiluminescent assay validated for clinical use on automated laboratory platforms. Plasma vitamin D levels were below the sufficiency threshold. Notably, 25(OH)D concentrations were significantly lower in patients who experienced a negative outcome (11.10 [8.80–16.20] vs. 15.25 [9.90–24.80] ng/mL, p = 0.0450) and significantly higher in patients with rapid clinical recovery (15.25 [10.70–24.80] vs. 13.30 [7.47–19.60] ng/mL, p = 0.0446) compared with all other patients. Through multivariable logistic regression analysis, higher 25(OH)D levels at the time of hospitalization were confirmed as an independent predictor of favorable outcome. A plasma 25(OH)D concentration above 11.10 ng/mL predicted favorable disease resolution, with a positive likelihood ratio of 1.40 (IQR: 1.05–1.87). In conclusion, our findings support plasma vitamin D levels as an independent predictor of clinical outcomes in patients hospitalized with COVID-19 pneumonia.

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07–7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19–7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation.

More than three years have passed since the first case, and COVID-19 is still a health concern, with several open issues such as the lack of reliable predictors of a patient’s outcome. Osteopontin (OPN) is involved in inflammatory response to infection and in thrombosis driven by chronic inflammation, thus being a potential biomarker for COVID-19. The aim of the study was to evaluate OPN for predicting negative (death or need of ICU admission) or positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. We enrolled 133 hospitalized, moderate-to-severe COVID-19 patients in a prospective observational study between January and May 2021. Circulating OPN levels were measured by ELISA at admission and at day 7. The results showed a significant correlation between higher plasma concentrations of OPN at hospital admission and a worsening clinical condition. At multivariate analysis, after correction for demographic (age and gender) and variables of disease severity (NEWS2 and PiO2/FiO2), OPN measured at baseline predicted an adverse prognosis with an odds ratio of 1.01 (C.I. 1.0–1.01). At ROC curve analysis, baseline OPN levels higher than 437 ng/mL predicted a severe disease evolution with 53% sensitivity and 83% specificity (area under the curve 0.649, p = 0.011, likelihood ratio of 1.76, (95% confidence interval (CI): 1.35–2.28)). Our data show that OPN levels determined at the admission to hospital wards might represent a promising biomarker for early stratification of patients’ COVID-19 severity. Taken together, these results highlight the involvement of OPN in COVID-19 evolution, especially in dysregulated immune response conditions, and the possible use of OPN measurements as a prognostic tool in COVID-19.

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO 2 /FiO 2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Research into effective predictive markers and therapeutic interventions for COVID-19 remains of considerable interest. Vitamin D may be relevant, especially in frail populations in whom deficiency is more prevalent. In this prospective observational cohort study, 139 patients with moderate-to-severe COVID-19 who were hospitalized during the third wave of the pandemic in Italy were enrolled. Plasma vitamin D concentrations (both 25-hydroxyvitamin D-25(OH)D and 1,25-dihydroxyvitamin D-1,25(OH)[sub.2]D) together with parathyroid hormone levels were measured using a chemiluminescent assay validated for clinical use on automated laboratory platforms. Plasma vitamin D levels were below the sufficiency threshold. Notably, 25(OH)D concentrations were significantly lower in patients who experienced a negative outcome (11.10 [8.80–16.20] vs. 15.25 [9.90–24.80] ng/mL, p = 0.0450) and significantly higher in patients with rapid clinical recovery (15.25 [10.70–24.80] vs. 13.30 [7.47–19.60] ng/mL, p = 0.0446) compared with all other patients. Through multivariable logistic regression analysis, higher 25(OH)D levels at the time of hospitalization were confirmed as an independent predictor of favorable outcome. A plasma 25(OH)D concentration above 11.10 ng/mL predicted favorable disease resolution, with a positive likelihood ratio of 1.40 (IQR: 1.05–1.87). In conclusion, our findings support plasma vitamin D levels as an independent predictor of clinical outcomes in patients hospitalized with COVID-19 pneumonia.

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

The International Gamma-ray Astrophysics Laboratory (INTEGRAL) has been surveying the sky above 20 keV since its launch in 2002 providing new insights into the nature of the sources that populate our Universe at soft gamma-ray energies. The latest IBIS/ISGRI survey lists 929 hard X-ray sources, of which 113 are reported as unidentified, i.e. lacking a lower energy counterpart or simply not studied in other wavebands. To overcome this lack of information, we either browsed the X-ray archives, or, if no data in the X-ray band were available, we requested Target of Opportunity (ToO) observations with the X-ray Telescope (XRT) on-board the Neil Gehrels Swift Observatory. Following this approach, we selected a sample of 10 objects for which X-ray data were key to investigate their nature. We found a single X-ray association for all of the sources, except for IGR J16267-3303, for which two X-ray detections were spotted within the IBIS positional uncertainty. We then browsed multi-waveband archives to search for counterparts to these X-ray detections at other wavelengths and analysed X-ray spectral properties to determine their nature and association with the high-energy emitter. As a result of our analysis, we identified the most likely counterpart for 7 sources, although in some cases its nature/class could not be definitely assessed on the basis of the information collected. Interestingly, SWIFT J2221.6+5952, first reported in the 105-month Swift/Burst Alert Telescope (BAT) survey, is the only source of the sample for which we did not find any counterpart at radio/optical/IR wavebands. Finally, we found that two IBIS source, IGR J17449-3037 and IGR J17596-2315 are positionally associated with a Fermi Large Area Telescope (LAT) object.

We report results of a systematic study of the broad--band (2--2000 keV) time--resolved prompt emission spectra of a sample of Gamma-Ray Bursts (GRBs) detected with both the Wide Field Cameras (WFCs) aboard the BeppoSAX satellite and the BATSE experiment aboard CGRO. The main goal of the paper is to test spectral models of the GRB prompt emission that have recently been proposed. In particular, we test the photospheric model proposed by Ryde and Pe'er (2009), i.e., blackbody plus power--law, the addition of a blackbody emission to the Band function in the cases in which this function does not fit the data, and the Comptonization model developed by Titarchuk et al. (2012). By considering the few spectra for which the simple Band function does not provide a fully acceptable fit to the data (Frontera et al. 2012), only in one case we find a statistically significant better fit by adding a blackbody to this function. We confirm the results found fitting the BATSE spectra alone with a blackbody plus a power law. Instead when the BATSE GRB spectra are joined to those obtained with WFCs (2--28 keV), this model becomes unacceptable in most of time intervals in which we subdivide the GRB light curves. We find instead that the Comptonization model is always acceptable, even in the few cases in which the Band function is inconsistent with the data. We discuss the implications of these results.

Many sources in the fourth INTEGRAL/IBIS catalogue are still unidentified, since they lack an optical counterpart. An important tool that can help in identifying/classifying these sources is the cross-correlation with radio catalogues, which are very sensitive and positionally accurate. Moreover, the radio properties of a source, such as the spectrum or morphology, could provide further insight into its nature. Flat-spectrum radio sources at high Galactic latitudes are likely to be AGN, possibly associated to a blazar or to the compact core of a radio galaxy. Here we present a small sample of 6 sources extracted from the fourth INTEGRAL/IBIS catalogue that are still unidentified/unclassified, but which are very likely associated with a bright, flat-spectrum radio object. To confirm the association and to study the source X-ray spectral parameters, we performed X-ray follow-up observations with Swift/XRT. We report the results obtained from this search and discuss the nature of each source. 5 of the 6 radio associations are also detected in X-rays; in 3 cases they are the only counterpart found. IGR J06073--0024 is a flat-spectrum radio quasar at z=1.08, IGR J14488--4008 is a newly discovered radio galaxy, while IGR J18129--0649 is an AGN of a still unknown type. The nature of IGR J07225--3810 and IGR J19386--4653 is less well defined, since in both cases we find another X-ray source in the INTEGRAL error circle; nevertheless, the flat-spectrum radio source, likely to be a radio loud AGN, remains a viable and more convincing association in both cases. Only for IGR J11544--7618 could we not find any convincing counterpart since the radio association is not an X-ray emitter.

A short replay to the comment of Rossetti & Molendi (astro-ph/0702417) in answer to the paper of Fusco-Femiano, Landi & Orlandini 2007 regarding the presence of a nonthermal component in the Coma Cluster spectrum.