Non-Infectious Pneumonitis and Acute Respiratory Distress Syndrome in a Patient on Ustekinumab Treatment: Case Report and Literature Review.

Ustekinumab is a monoclonal antibody targeting the p40 subunit of IL-12 and IL-23, approved for treating psoriasis, psoriatic arthritis, and inflammatory bowel disease. Despite a remarkable success in treating chronic inflammatory conditions and a generally favorable safety profile, its role in inducing rare adverse events, such as interstitial pneumonia and acute respiratory distress syndrome (ARDS), remains largely uncharted. We report a case of a 66-year-old male patient treated with Ustekinumab for severe psoriasis who, after almost two years of treatment, developed dyspnea, asthenia, and fever progressing to non-infectious pneumonia and ARDS leading to ICU admission. Moreover, we conducted a literature review on Ustekinumab-associated pulmonary complications. Our case underscores the importance of appropriate and long-term clinical monitoring in patients on Ustekinumab treatment, particularly considering the potential lung complications. The possibility of non-infectious pneumonitis should be considered alongside infectious causes, facilitating prompt management in the case of negative infectious screening. Additionally, the severity of ARDS underscores the importance of timely recognition and proper management. Further investigations are recommended to investigate the immunological basis of Ustekinumab-induced ARDS for designing appropriate monitoring strategies.

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.

Self-harm by single- and multi-agent medication poisoning in a retrospective analysis of a Poison Control Center database from January 2018 to December 2022.

PURPOSE: Medication poisoning is the most common method of self-harm. Longitudinal studies incorporating pre- and post-COVID-19 pandemic data are required to describe the phenomenon and to evaluate the long-term impact on mental health. METHODS: Calls to the Poison Control Center of Policlinico Umberto I Hospital - Sapienza University of Rome, Italy, were analyzed retrospectively for characteristics and clinical presentation of cases of interest from January 2018 to December 2022. RESULTS: A total of 756 cases of self-harm by medication poisonings were recorded in the study period. A reduction in rate of cases in 2020 was followed by a return to pre-pandemic levels by 2021. When separately analyzing single- and multi-agent cases, occurrence of cases involving just one medication increased since early 2021, with a peak in 2022 (7.8% of total calls, 95% CI 6.2-9.5, from 4.9%, 95% CI 4.1-5.8 in 2018). This increase in the rate of cases, mostly of none or mild severity, was driven by youth aged 12-21, in which the relative proportion of single- versus multi-agent cases showed an increasing trend since 2020 (from 42.6% in 2018 to 78.6% in 2022). Acetaminophen was the medication most frequently involved and benzodiazepines the largest class. A psychiatric background was increasingly seen in 2022, especially in age group 12-21. CONCLUSION: Single-agent medication self-harm may be an increasingly prevailing phenomenon. Young adolescents with a psychiatric background might be most vulnerable to this behavior in the COVID-19 pandemic aftermath. Healthcare professionals should expect favorable clinical outcome and improve both counseling and psychotherapy supervision in individuals at risk.

[ANMCO/SIMEU Consensus document on the use of reversal agents of antithrombotic therapies in patients with active bleeding or at high-risk of major bleeding events]. / Documento di consenso ANMCO/SIMEU sull'impiego degli agenti di reversione delle terapie antitrombotiche nei pazienti con sanguinamento in atto o ad alto rischio di eventi emorragici.

In recent decades, an incredible evolution in antithrombotic therapies for the treatment of patients suffering from atherosclerosis, atrial fibrillation and venous thromboembolism occurred, leading to the availability of increasingly safe drugs. However, bleeding complications associated with these drugs still have an important health, social and economic impact. Recently, with the aim of improving the acute management of patients with or at risk of major bleeding events, specific reversal agents of antithrombotic drugs have been developed. Although these agents have demonstrated their effectiveness in small pharmacodynamic studies or clinical trials, it is important to consider that the benefit of reversal of an antiplatelet or anticoagulant drug must always be counterbalanced by the possible prothrombotic effect caused by the removal of antithrombotic protection as well as by prothrombotic mechanisms related to bleeding, major surgery or trauma.In this ANMCO/SIMEU consensus document we summarize the main characteristics and efficacy studies of the currently available reversal agents and present practical flow-charts in which we suggest their possible use in patients with active bleeding or at high risk of major bleeding events.

Modified sympathicotomy in patients with refractory ventricular tachycardia and structural heart disease: a single-center experience.

BACKGROUND: Modified cardiac sympathetic denervation (CSD) with stellate ganglion (SG) sparing is a novel technique for cardiac neuromodulation in patients with refractory ventricular tachycardia (VT). OBJECTIVES: Our aim is to describe the mid- to long-term clinical outcome of the modified CSD with SG sparing in a series of patients with structural heart disease (SHD) and refractory VT. METHODS: All consecutive patients with SHD and refractory VT undergoing modified CSD were enrolled. Baseline clinical characteristics and periprocedural data were collected for all patients. The primary outcome was any recurrence of sustained VT. RESULTS: We enrolled 15 patients (age: 69.2 ± 7.9 years; male 100%) undergoing modified CSD. Left ventricular ejection fraction was 37 ± 11% and all patients had an implantable cardiac defibrillator (ICD); the underlying cardiomyopathy was non-ischemic in 73.3% of them. At least one previous ablation had been attempted in 66.6% of cases. The 73.3% of patients underwent bilateral CSD and the mean effective surgical time was 10.8 ± 2.4 min per side; no major periprocedural complication occurred. After a median follow-up time of 15 months (IQR: 8.5-24.5 months), the primary outcome occurred in 47.6% of cases. All patients experienced a reduction of ICD shocks after CSD (3.1 ICD shocks/patient before vs. 0.3 ICD shocks/patient after CSD; p-value: 0.001). Bilateral CSD and a VT cycle length < 340 ms were associated with better outcomes. CONCLUSIONS: A modified CSD approach with stellate ganglion sparing appears to be safe, fast, and effective in the treatment of patients with SHD and refractory VTs.

Special Issue "Clinical Consequences of COVID-19": Taking a Look at Complexity.

The consequences of SARS-CoV-2 infection are far from being fully understood or accounted for [...].

Genotypic Evolution of Klebsiella pneumoniae Sequence Type 512 during Ceftazidime/Avibactam, Meropenem/Vaborbactam, and Cefiderocol Treatment, Italy.

In February 2022, a critically ill patient colonized with a carbapenem-resistant K. pneumoniae producing KPC-3 and VIM-1 carbapenemases was hospitalized for SARS-CoV-2 in the intensive care unit of Policlinico Umberto I hospital in Rome, Italy. During 95 days of hospitalization, ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol were administered consecutively to treat 3 respiratory tract infections sustained by different bacterial agents. Those therapies altered the resistome of K. pneumoniae sequence type 512 colonizing or infecting the patient during the hospitalization period. In vivo evolution of the K. pneumoniae sequence type 512 resistome occurred through plasmid loss, outer membrane porin alteration, and a nonsense mutation in the cirA siderophore gene, resulting in high levels of cefiderocol resistance. Cross-selection can occur between K. pneumoniae and treatments prescribed for other infective agents. K. pneumoniae can stably colonize a patient, and antimicrobial-selective pressure can promote progressive K. pneumoniae resistome evolution, indicating a substantial public health threat.

Reduced Reliability of Procalcitonin (PCT) as a Biomarker of Bacterial Superinfection: Concerns about PCT-Driven Antibiotic Stewardship in Critically Ill COVID-19 Patients-Results from a Retrospective Observational Study in Intensive Care Units.

BACKGROUND: The aim of this study was to assess whether procalcitonin levels is a diagnostic tool capable of accurately identifying sepsis and ventilator-associated pneumonia (VAP) even in critically ill COVID-19 patients. METHODS: In this retrospective, observational study, all critically ill COVID-19 patients who survived for ≥2 days in a single university hospital and had at least one serum procalcitonin (PCT) value and associated blood culture and/or culture from a lower respiratory tract specimen available were eligible for the study. RESULTS: Over the research period, 184 patients were recruited; 67 VAP/BSI occurred, with an incidence rate of 21.82 episodes of VAP/BSI (95% CI: 17.18-27.73) per 1000 patient-days among patients who were included. At the time of a positive microbiological culture, an average PCT level of 1.25-3.2 ng/mL was found. Moreover, also in subjects without positive cultures, PCT was altered in 21.7% of determinations, with an average value of 1.04-5.5 ng/mL. Both PCT and PCT-72 h were not linked to a diagnosis of VAP/BSI in COVID-19 patients, according to the multivariable GEE models (aOR 1.13, 95% CI 0.51-2.52 for PCT; aOR 1.32, 95% CI 0.66-2.64 for PCT-72 h). CONCLUSION: Elevated PCT levels might not always indicate bacterial superinfections or coinfections in a severe COVID-19 setting.

Biomarkers of Neurological Damage: From Acute Stage to Post-Acute Sequelae of COVID-19.

Background: Neurological symptoms (NS) in COVID-19 are related to both acute stage and long-COVID. We explored levels of brain injury biomarkers (NfL and GFAP) and myeloid activation marker (sCD163) and their implications on the CNS. Materials and Methods: In hospitalized COVID-19 patients plasma samples were collected at two time points: on hospital admission (baseline) and three months after hospital discharge (Tpost). Patients were stratified according to COVID-19 severity based on acute respiratory distress syndrome (ARDS) onset (severe and non-severe groups). A further stratification according to the presence of NS (with and without groups) at baseline (requiring a puncture lumbar for diagnostic purposes) and according to NS self-referred at Tpost was performed. Finally, cerebrospinal fluid (CSF) samples were collected from patients with NS present at baseline. Results: We enrolled 144 COVID-19 patients (62 female/82 male; median age [interquartile range, IQR]): 64 [55-77]) and 53 heathy donors (HD, 30 female/23 male; median age [IQR]: 64 [59-69]). At baseline, higher plasma levels of NfL, GFAP and sCD163 in COVID-19 patients compared to HD were observed (p < 0.0001, p < 0.0001 and p < 0.0001, respectively), especially in those with severe COVID-19 (p < 0.0001, p < 0.0001 and p < 0.0001, respectively). Patients with NS showed higher plasma levels of NfL, GFAP and sCD163 compared to those without (p = 0.0023, p < 0.0001 and 0.0370, respectively). At baseline, in COVID-19 patients with NS, positive correlations between CSF levels of sCD163 and CSF levels of NfL (ρ = 0.7536, p = 0.0017) and GFAP were observed (ρ = 0.7036, p = 0.0045). At Tpost, the longitudinal evaluation performed on 77 COVID-19 patients showed a significant reduction in plasma levels of NfL, GFAP and sCD163 compared to baseline (p < 0.0001, p < 0.0001 and p = 0.0413, respectively). Finally, at Tpost, in the severe group, higher plasma levels of sCD163 in patients with NS compared to those without were reported (p < 0.0001). Conclusions: High plasma levels of NfL, GFAP and sCD163 could be due to a proinflammatory systemic and brain response involving microglial activation and subsequent CNS damage. Our data highlight the association between myeloid activation and CNS perturbations.

Tissue Inhibitor of Matrix Metalloproteinases-1 (TIMP-1) and Pulmonary Involvement in COVID-19 Pneumonia.

Background: The aim of the study was to longitudinally evaluate the association between MMP-2, MMP-9, TIMP-1 and chest radiological findings in COVID-19 patients. Methods: COVID-19 patients were evaluated based on their hospital admission (baseline) and three months after hospital discharge (T post) and were stratified into ARDS and non-ARDS groups. As a control group, healthy donors (HD) were enrolled. Results: At the baseline, compared to HD (n = 53), COVID-19 patients (n = 129) showed higher plasma levels of MMP-9 (p < 0.0001) and TIMP-1 (p < 0.0001) and the higher plasma activity of MMP-2 (p < 0.0001) and MMP-9 (p < 0.0001). In the ARDS group, higher plasma levels of MMP-9 (p = 0.0339) and TIMP-1 (p = 0.0044) and the plasma activity of MMP-2 (p = 0.0258) and MMP-9 (p = 0.0021) compared to non-ARDS was observed. A positive correlation between the plasma levels of TIMP-1 and chest computed tomography (CT) score (ρ = 0.2302, p = 0.0160) was observed. At the T post, a reduction in plasma levels of TIMP-1 (p < 0.0001), whereas an increase in the plasma levels of MMP-9 was observed (p = 0.0088). Conclusions: The positive correlation between TIMP-1 with chest CT scores highlights its potential use as a marker of fibrotic burden. At T post, the increase in plasma levels of MMP-9 and the reduction in plasma levels of TIMP-1 suggested that inflammation and fibrosis resolution were still ongoing.

Adult 10-year survivors after liver transplantation: a single-institution experience over 40 years.

Liver transplantation (LT) represents the best cure for several acute and chronic liver diseases. Several studies reported excellent mid-term survivals after LT. However, lesser evidence has been reported on very long (10- and 20-year) follow-up results. This study aims to analyze the monocentric LT experience of the Sapienza University of Rome to identify the pre-operatively available parameters limiting a 10-year post-transplant survival. A total of 491 patients transplanted between 1982 and 2012 were enrolled. The cohort was split into two groups, namely the Short Surviving Group (< 10 years; n = 228, 46.4%) and the Long Surviving Group (≥ 10 years; n = 263, 53.6%). Several differences were reported between the two groups regarding initial liver function, surgical techniques adopted, and immunosuppression. Four variables emerged as statistically relevant as independent risk factors for not reaching at least 10 years of follow-up: recipient age (OR = 1.02; P = 0.01), donor age (OR = 1.01; P = 0.03), being transplanted during the eighties (OR = 6.46; P < 0.0001) and nineties (OR = 2.63; P < 0.0001), and the UNOS status 1-2A (OR = 2.62; P < 0.0001). LT confirms to be an extraordinary therapy for several severe liver diseases, consenting to reach in half of the transplanted cases even more than 20 years of follow-up. The initial liver function and the donor and recipient ages are relevant in impacting long-term survival after transplantation. A broad commitment from many professional groups, including surgeons, hepatologists, and anesthesiologists, is necessary. The achievement of excellent results in terms of long-term survival is proof of the effectiveness of this multidisciplinary collaboration.

Endoscopic full-thickness resection versus endoscopic submucosal dissection for challenging colorectal lesions: a randomized trial.

BACKGROUND AND AIMS: The optimal endoscopic resection method of challenging colorectal lesions (ie, adenomatous recurrences, nongranular laterally spreading tumors [LST-NGs], lesions without lifting sign <30 mm) is still under debate. The aim of this study was to directly compare endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (EFTR) for the resection of challenging colorectal lesions in a randomized trial. METHODS: A multicenter, prospective, randomized study was performed in 4 Italian referral centers. Consecutive patients referred for endoscopic resection of challenging lesions were randomly assigned to undergo EFTR or ESD. Primary outcomes were complete (R0) resection and en bloc resection of lesions. Technical success, procedure time, procedure speed, area of the resected specimen, adverse event rate, and local recurrence rate at 6 months were also compared. RESULTS: Overall, 90 patients were included in the study, equally representing the 3 challenging lesion types. Age and sex were comparable in the 2 groups. En bloc resection was obtained in 95.5% of the EFTR group and in 93.3% of the ESD group. R0 resection rate was comparable in the 2 groups (EFTR vs ESD, 42 [93.3%] vs 36 [80%]; P = .06). The EFTR group exhibited a significantly shorter total procedure time (25.6 ± 10.6 minutes vs 76.7 ± 26.4 minutes, P ≤ .01), as well as overall procedure speed (16.8 ± 11.8 mm2/min vs 11.9 ± 9.2 mm2/min, P = .03). The EFTR group had a significantly smaller mean lesion size (21.6 ± 8.3 mm vs 28.7 ± 7.7 mm, P ≤ .01). Adverse events were reported less frequently in patients in the EFTR group (4.44% vs 15.5%, P = .04). CONCLUSIONS: EFTR is comparable to ESD in the treatment of challenging colorectal lesions in terms of safety and efficacy. EFTR is considerably faster than ESD in the treatment of nonlifting lesions and adenoma recurrences. (Clinical trial registration number: NCT05502276.).

ANMCO-SIMEU consensus document: appropriate management of atrial fibrillation in the emergency department.

Atrial fibrillation (AF) accounts for 2% of the total presentations to the emergency department (ED) and represents the most frequent arrhythmic cause for hospitalization. It steadily increases the risk of thromboembolic events and is often associated with several comorbidities that negatively affect patient's quality of life and prognosis. AF has a considerable impact on healthcare resources, making the promotion of an adequate and coordinated management of this arrhythmia necessary in order to avoid clinical complications and to implement the adoption of appropriate technological and pharmacological treatment options. AF management varies across regions and hospitals and there is also heterogeneity in the use of anticoagulation and electric cardioversion, with limited use of direct oral anticoagulants. The ED represents the first access point for early management of patients with AF. The appropriate management of this arrhythmia in the acute setting has a great impact on improving patient's quality of life and outcomes as well as on rationalization of the financial resources related to the clinical course of AF. Therefore, physicians should provide a well-structured clinical and diagnostic pathway for patients with AF who are admitted to the ED. This should be based on a tight and propositional collaboration among several specialists, i.e. the ED physician, cardiologist, internal medicine physician, anesthesiologist. The aim of this ANMCO-SIMEU consensus document is to provide shared recommendations for promoting an integrated, accurate, and up-to-date management of patients with AF admitted to the ED or Cardiology Department, in order to make it homogeneous across the national territory.

Endoscopic entero-enteral bypass to treat postsurgical benign complications of hepatico-jejunostomy: Update of a 7-year single-center experience.

Background and study aims Since 2014, we have been using a new endoscopic approach to improve management of biliary adverse events (BAEs) after bilio-digestive anastomosis. We provide an update about our experience at 7 years. Patients and methods Patients with BAEs on hepatico-jejunostomy underwent entero-enteral endoscopic by-pass (EEEB) creation between the duodenal/gastric wall and the biliary jejunal loop. Evaluation of results during our seven-year experience was performed. Results Eighty consecutive patients (32 patients from Jan 2014 to Dec 2017 and 48 patients from Jan 2018 to Jan 2021) underwent EEEB, which was successful in all but one patient. The cumulative AEs rate was 32 %. Endoscopic retrograde cholangiography (ERC) through the EEEB successfully treated all types of BAEs in these patients. Cumulative disease recurrence was 3.8 % (three patients) and was retreated through the EEEB. Conclusions The update of our experience with EEEB confirmed that in patients with BAEs after bilio-digestive anastomosis, EEEB allows successful long-term treatment of different BAEs in a tertiary referral center with an acceptable rate of related AEs.

Endoscopic Submucosal Dissection for Subepithelial Tumor Treatment in the Upper Digestive Tract: A Western, Multicenter Study.

Background/Aims: Endoscopic submucosal dissection (ESD) has been proposed for removal of gastrointestinal subepithelial tumors (GI-SETs), but data are still scanty. This study aimed to report a case series from a western country. Patients and Methods: Data of patients with upper GI-SETs suitable for ESD removal observed in 4 centers were retrospectively reviewed. Before endoscopic procedure, the lesion was characterized by endosonographic evaluation, histology, and CT scan. The en bloc resection and the R0 resection rates were calculated, as well as incidence of complications, and the 1-year follow-up was reported. Results: Data of 84 patients with esophageal (N = 13), gastric (N = 61), and duodenal (N = 10) GI-SETs were collected. The mean diameter of lesions was 26 mm (range: 12-110 mm). There were 17 gastrointestinal stromal tumors, 12 neuroendocrine tumors, 35 leiomyomas, 18 lipomas, and 2 hamartomas. En bloc and R0 resection were achieved in 83 (98.8%) and in 80 (95.2%) patients, respectively. Overall, a complication occurred in 11 (13.1%) patients, including bleeding (N = 7) and perforation (N = 4). Endoscopic approach was successful in all bleedings, but 1 patient who required radiological embolization, and in 2 perforations, while surgery was performed in the other patients. Overall, a surgical approach was eventually needed in 5 (5.9%), including 3 in whom R0 resection failed and 2 with perforation. Conclusions: Our study found that ESD may be an effective and safe alternative to surgical intervention for both benign and localized malignant GI-SETs.

Introdução/objetivos: A dissecção endoscópica da submucosa (ESD) tem sido proposta para a exérese de tumores subepiteliais gastrointestinais (GI-SETs), embora a literatura seja escassa. Este estudo teve como objetivo reportar uma série de casos de um país ocidental. Métodos: Coorte retrospectiva incluindo doentes com SETs do tubo digestivo superior submetidos a ESD em 4 centros (1 ano de follow-up). Antes do procedimento, a lesão foi caracterizada por ecoendoscopia, histologia e tomografia computadorizada. Foram avaliadas as taxas de ressecção em bloco e R0, bem como a incidência de complicações. Resultados: Incluídos 84 doentes com GI-SETs esofágicos (N = 13), gástricos (N = 61) e duodenais (N = 10). O diâmetro médio das lesões foi de 26 mm (intervalo 12­110 mm) ­ 17 tumores do estroma gastrointestinal, 12 tumores neuroendócrinos, 35 leiomiomas, 18 lipomas e 2 hamartomas. A resseção foi em bloco e R0 em 83 (98.8%) e em 80 (95.2%) doentes, respectivamente. Globalmente, ocorreram complicações em 11 (13.1%) doentes, incluindo hemorragia (N = 7) e perfuração (N = 4). A terapêutica endoscópica foi eficaz em todas as hemorragias exceto em 1 doente que necessitou de embolização radiológica e em 2 perfurações (submetidas a cirurgia). No geral, a abordagem cirúrgica foi necessária em 5 (5.9%) ­ 3 doentes com resseção R1 e 2 com perfuração. Conclusões: A ESD pode ser uma alternativa eficaz e segura à intervenção cirúrgica para GI-SETs benignos e malignos localizados.

Blood Biomarkers from the Emergency Department Disclose Severe Omicron COVID-19-Associated Outcomes.

BACKGROUND: Since its outbreak, Coronavirus disease 2019 (COVID-19), a life-threatening respiratory illness, has rapidly become a public health emergency with a devastating social impact. Lately, the Omicron strain is considered the main variant of concern. Routine blood biomarkers are, indeed, essential for stratifying patients at risk of severe outcomes, and a huge amount of data is available in the literature, mainly for the previous variants. However, only a few studies are available on early routine biochemical blood biomarkers for Omicron-afflicted patients. Thus, the aim and novelty of this study were to identify routine blood biomarkers detected at the emergency room for the early prediction of severe morbidity and/or mortality. METHODS: 449 COVID-19 patients from Sapienza University Hospital of Rome were divided into four groups: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients that after the admission in the emergency department were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency department required intensive assistance); (4) the deceased group (patients that after the admission in the emergency department had a fatal outcome). RESULTS: ANOVA and ROC data showed that high-sensitivity troponin-T (TnT), fibrinogen, glycemia, C-reactive protein, lactate dehydrogenase, albumin, D-dimer myoglobin, and ferritin for both men and women may predict lethal outcomes already at the level of the emergency department. CONCLUSIONS: Compared to previous Delta COVID-19 parallel emergency patterns of prediction, Omicron-induced changes in TnT may be considered other early predictors of severe outcomes.

Cellular Immune Profiling of Lung and Blood Compartments in Patients with SARS-CoV-2 Infection.

BACKGROUND: SARS-CoV-2 related immunopathology may be the driving cause underlying severe COVID-19. Through an immunophenotyping analysis on paired bronchoalveolar lavage fluid (BALF) and blood samples collected from mechanically ventilated patients with COVID-19-associated Acute Respiratory Distress Syndrome (CARDS), this study aimed to evaluate the cellular immune responses in survivors and non-survivors of COVID-19. METHODS: A total of 36 paired clinical samples of bronchoalveolar lavage fluid (BALF) mononuclear cells (BALF-MC) and peripheral blood mononuclear cells (PBMC) were collected from 18 SARS-CoV-2-infected subjects admitted to the intensive care unit (ICU) of the Policlinico Umberto I, Sapienza University Hospital in Rome (Italy) for severe interstitial pneumonia. The frequencies of monocytes (total, classical, intermediate and non-classical) and Natural Killer (NK) cell subsets (total, CD56bright and CD56dim), as well as CD4+ and CD8+ T cell subsets [naïve, central memory (TCM) and effector memory (TEM)], and those expressing CD38 and/or HLADR were evaluated by multiparametric flow cytometry. RESULTS: Survivors with CARDS exhibited higher frequencies of classical monocytes in blood compared to non-survivors (p < 0.05), while no differences in the frequencies of the other monocytes, NK cell and T cell subsets were recorded between these two groups of patients (p > 0.05). The only exception was for peripheral naïve CD4+ T cells levels that were reduced in non-survivors (p = 0.04). An increase in the levels of CD56bright (p = 0.012) and a decrease in CD56dim (p = 0.002) NK cell frequencies was also observed in BALF-MC samples compared to PBMC in deceased COVID-19 patients. Total CD4+ and CD8+ T cell levels in the lung compartment were lower compared to blood (p = 0.002 and p < 0.01, respectively) among non-survivors. Moreover, CD38 and HLA-DR were differentially expressed by CD4+ and CD8+ T cell subsets in BALF-MC and in PBMC among SARS-CoV-2-infected patients who died from COVID-19 (p < 0.05). CONCLUSIONS: These results show that the immune cellular profile in blood and pulmonary compartments was similar in survivors and non-survivors of COVID-19. T lymphocyte levels were reduced, but resulted highly immune-activated in the lung compartment of patients who faced a fatal outcome.