Circulating extracellular particles from severe COVID-19 patients show altered profiling and innate lymphoid cell-modulating ability.

Introduction: Extracellular vesicles (EVs) and particles (EPs) represent reliable biomarkers for disease detection. Their role in the inflammatory microenvironment of severe COVID-19 patients is not well determined. Here, we characterized the immunophenotype, the lipidomic cargo and the functional activity of circulating EPs from severe COVID-19 patients (Co-19-EPs) and healthy controls (HC-EPs) correlating the data with the clinical parameters including the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) and the sequential organ failure assessment (SOFA) score. Methods: Peripheral blood (PB) was collected from COVID-19 patients (n=10) and HC (n=10). EPs were purified from platelet-poor plasma by size exclusion chromatography (SEC) and ultrafiltration. Plasma cytokines and EPs were characterized by multiplex bead-based assay. Quantitative lipidomic profiling of EPs was performed by liquid chromatography/mass spectrometry combined with quadrupole time-of-flight (LC/MS Q-TOF). Innate lymphoid cells (ILC) were characterized by flow cytometry after co-cultures with HC-EPs or Co-19-EPs. Results: We observed that EPs from severe COVID-19 patients: 1) display an altered surface signature as assessed by multiplex protein analysis; 2) are characterized by distinct lipidomic profiling; 3) show correlations between lipidomic profiling and disease aggressiveness scores; 4) fail to dampen type 2 innate lymphoid cells (ILC2) cytokine secretion. As a consequence, ILC2 from severe COVID-19 patients show a more activated phenotype due to the presence of Co-19-EPs. Discussion: In summary, these data highlight that abnormal circulating EPs promote ILC2-driven inflammatory signals in severe COVID-19 patients and support further exploration to unravel the role of EPs (and EVs) in COVID-19 pathogenesis.

SARS-CoV-2 Infection in Health Care Workers of Trieste (North-Eastern Italy), 1 October 2020-7 February 2022: Occupational Risk and the Impact of the Omicron Variant.

Vaccination coverage against COVID-19 among health care workers (HCWs) of the University Health Agency Giuliano-Isontina (ASUGI) of Trieste (North-eastern Italy) by 1 January 2022 was 90.4% with at least one vaccine dose, 84.9% with at least 2 doses, and 75.1% with 3 doses, 98.2% with Comirnaty (Pfizer BioNtech, New York, NY, USA) versus 1.8% with Spikevax (Moderna, Cambridge, MA, USA). From 1 October 2020 to 7 February 2022, 1652 SARS-CoV-2 infections were notified in HCWs of ASUGI Trieste. Although the overall risk of SARS-CoV-2 contagion increased over time, the rate of occupational infections progressively declined, from 42.5% during the second COVID-19 wave to 15.6% in the fifth. Between 1 January-7 February 2022 (a period dominated by the Omicron variant), albeit no COVID-19-associated hospitalizations were recorded in HCWs of ASUGI Trieste, 669 SARS-CoV-2 infections were counted against 367 cases observed from 1 October to 31 December 2020, the 3 months preceding the implementation of the vaccination campaign against COVID-19. Job tasks and health care settings turned out to be the most significant risk factors for SARS-CoV-2 infection. However, the effect of workplace prevailed over job task on the biological risk, with greater rates of SARS-CoV-2 infections observed among HCWs operating in areas with higher levels of circulation of the virus, particularly COVID-19 dedicated units.

Immune thrombotic thrombocytopenic purpura: Personalized therapy using ADAMTS-13 activity and autoantibodies.

Recently, treatment of immune-mediated thrombotic thrombocytopenic purpura (ITTP) has changed with the advent of caplacizumab in clinical practice. The International Working Group (IWG) has recently integrated the ADAMTS-13 activity/autoantibody monitoring in consensus outcome definitions. We report three ITTP cases during the coronavirus disease 2019 pandemic, that received a systematic evaluation of ADAMTS-13 activity and autoantibodies. We describe how the introduction of caplacizumab and ADAMTS-13 monitoring could change the management of ITTP patients and discuss whether therapeutic choices should be based on the clinical response alone. ADAMTS-13 activity/antibodies were assessed every 5 days. Responses were evaluated according to updated IWG outcome definitions. These kinetics, rather than clinical remission, guided the therapy, allowing early and safe caplacizumab discontinuation and sensible administration of rituximab. Caplacizumab was cautiously discontinued after achieving ADAMTS-13 complete remission. These cases illustrate that prospective ADAMTS-13 evaluation and use of updated IWG definitions may improve real-life patients' management in the caplacizumab era.

D-Dimer Tests in the Emergency Department: Current Insights.

In the Emergency Medicine setting, D-dimer is currently employed in the diagnostic assessment of suspected venous thromboembolism and aortic syndrome. The nonspecific symptoms reported by patients, like chest pain, dyspnea or syncope, uncover a wide range of differential diagnosis, spanning from mild to life-threatening conditions. Therefore, we assumed the perspective of the Emergency Physician and, in this narrative review, we reported a brief presentation of the epidemiology of these symptoms and the characteristics of patients, in whom we could suspect the aforementioned pathologies. We also reported in which patients D-dimer gives useful information. In fact, when the probability of the disease is high, the D-dimer level is futile. On the contrary, given the low specificity of the test, when the probability of the disease is very low, a false-positive value of the D-dimer only increases the risk of overtesting. Patients with low to moderate probability really benefit from the D-dimer testing, in order to prevent the execution of expensive and potentially dangerous imaging tests. In the second part of the review, we focused on the prognostic value of the test in septic patients. The early prognostic stratification of septic patients remains a challenge for the Emergency Physician, in the absence of a definite biomarker or score to rely on. Therefore, we need several parameters for the early identification of patients at risk of an adverse prognosis and the D-dimer may play a role in this demanding task. SARS COVID-19 patients represent an emerging reality, where the role of the D-dimer for prognostic stratification could be relevant. In fact, in patients with severe forms of this disease, the D-dimer reaches very high values, which appear to parallel the course of respiratory failure. Whether the test may add useful information for the management of these patients remains to be determined.

Chest Computed Tomography Scoring in Patients With Novel Coronavirus-infected Pneumonia: Correlation With Clinical and Laboratory Features and Disease Outcome.

BACKGROUND/AIM: This study investigated the correlation of chest computed tomography (CT), findings, graded using two different scoring methods, with clinical and laboratory features and disease outcome, including a novel clinical predictive score, in patients with novel coronavirus-infected pneumonia (NCIP). PATIENTS AND METHODS: In this retrospective, observational study, CT scan of 92 NCIP patients admitted to Policlinico Tor Vergata, were analyzed using a quantitative, computed-based and a semiquantitative, radiologist-assessed scoring system. Correlations of the two radiological scores with clinical and laboratory features, the CALL score, and their association with a composite adverse outcome were assessed. RESULTS: The two scores correlated significantly with each other (ρ=0.637, p<0.0001) and were independently associated with age, LDH, estimated glomerular filtration rate, diabetes, and with the composite outcome, which occurred in 24 patients. CONCLUSION: In NCIP patients, two different radiological scores correlated with each other and with several clinical, laboratory features, and the CALL score. The quantitative score was a better independent predictor of the composite adverse outcome than the semiquantitative score.