The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target. To date, the present study provides the largest untargeted metabolomics and lipidomics analysis of plasma from COVID-19 patients and control groups, identifying new mechanisms associated with the host response to COVID-19, potential plasma biomarkers, and therapeutic targets.

Sars-Cov-2 infection causes fever and cough that may rapidly lead to acute respiratory distress syndrome (ARDS). Few biomarkers have been identified but, unfortunately, these are individually poorly specific, and novel biomarkers are needed to better predict patient outcome. The aim of this study was to evaluate the diagnostic performance of circulating platelets (PLT)-derived extracellular vesicles (EVs) as biomarkers for Sars-Cov-2 infection, by setting a rapid and reliable test on unmanipulated blood samples. PLT-EVs were quantified by flow cytometry on two independent cohorts of Sars-CoV-2+ (n = 69), Sars-Cov-2− (n = 62) hospitalized patients, and healthy controls. Diagnostic performance of PLT-EVs was evaluated by receiver operating characteristic (ROC) curve. PLT-EVs count were higher in Sars-Cov-2+ compared to Sars-Cov-2− patients or HC. ROC analysis of the combined cohorts showed an AUC = 0.79 and an optimal cut-off value of 1472 EVs/μL, with 75% sensitivity and 74% specificity. These data suggest that PLT-EVs might be an interesting biomarker deserving further investigations to test their predictive power.

Aim We aim at characterising a large population of Coronavirus 19 (COVID-19) patients with moderate-to-severe hypoxemic acute respiratory failure (ARF) receiving CPAP outside intensive care unit (ICU), and ascertaining whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. Methods In this retrospective, multicentre cohort study, we included COVID-19 adult patients, treated with CPAP outside ICU for hypoxemic ARF from March 1^st to April 15^th, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay (LOS), and 60-day in-hospital mortality. Results The study includes 537 patients with a median age of 69 (IQR, 60–76) years. Males were 391 (73%). According to predefined CPAP therapeutic goal, 397 (74%) patients were included in full treatment subgroup, and 140 (26%) in the do-not intubate (DNI) subgroup. Median CPAP duration was 4 (IQR, 1–8) days, while hospital LOS 16 (IQR, 9–27) days. Sixty-day in-hospital mortality was overall 34% (95%CI, 0.304–0.384), and 21% (95%CI, 0.169–0.249) and 73% (95%CI, 0.648–0.787) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95%CI, 0.345–0.488) for 180 (45%) CPAP failures requiring intubation, while 2% (95%CI, 0.008–0.035) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality [HR, 1.093 (95%CI, 1.010–1.184)]. Conclusions We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host-response to infections. Osteopontin (OPN) is an extracellular matrix protein involved in the inflammatory response. Our aim was to evaluate the diagnostic and prognostic performance in sepsis of a single OPN determination in the Emergency Department (ED). We conducted a single-centre prospective observational study in an Italian ED where we enrolled 102 consecutive patients presenting with suspected infection and qSOFA ≥ 2. OPN plasma concentration was found to be an independent predictor of sepsis (OR = 1.020, 95% CI 1.002–1.039, p = 0.031) and the diagnostic receiver operating characteristic (ROC) curve resulted in an area under the curve (AUC) of 0.878. OPN levels were positively correlated to plasma creatinine (r = 0.401 with p = 0.0001), but this relation was not explained by the development of acute kidney injury (AKI), since no difference was found in OPN concentration between AKI and non-AKI patients. The analysis of 30-days mortality showed no significant difference in OPN levels between alive and dead patients (p = 0.482). In conclusion, a single determination of OPN concentration helped to identify patients with sepsis in the ED, but it was not able to predict poor prognosis in our cohort of patients.

Infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe respiratory tract damage and acute lung injury. Therefore, it is crucial to study breath-associated biofluids not only to investigate the breath’s biochemical changes caused by SARS-CoV-2 infection, but also to discover potential biomarkers for the development of new diagnostic tools. In the present study, we performed an untargeted metabolomics approach using a bidimensional gas chromatography mass spectrometer (GCxGC-TOFMS) on exhaled breath condensate (EBC) from COVID-19 patients and negative healthy subjects to identify new potential biomarkers for the noninvasive diagnosis and monitoring of the COVID-19 disease. The EBC analysis was further performed in patients with acute or acute-on-chronic cardiopulmonary edema (CPE) to assess the reliability of the identified biomarkers. Our findings demonstrated that an abundance of EBC fatty acids can be used to discriminate COVID-19 patients and that they may have a protective effect, thus suggesting their potential use as a preventive strategy against the infection.