Effects on Right Ventricular Function One Year after COVID-19-Related Pulmonary Embolism.

The aim of this study was to investigate the presence of subclinical cardiac dysfunction in recovered coronavirus disease 2019 (COVID-19) patients, who were stratified according to a previous diagnosis of pulmonary embolism (PE) as a complication of COVID-19 pneumonia. Out of 68 patients with SARS-CoV-2 pneumonia followed up for one year, 44 patients (mean age 58.4 ± 13.3, 70% males) without known cardiopulmonary disease were divided in two groups (PE+ and PE-, each comprising 22 patients) and underwent clinical and transthoracic echocardiographic examination, including right-ventricle global longitudinal strain (RV-GLS), and RV free wall longitudinal strain (RV-FWLS). While no significant differences were found in the left- or right-heart chambers' dimensions between the two study groups, the PE+ patients showed a significant reduction in RV-GLS (-16.4 ± 2.9 vs. -21.6 ± 4.3%, p < 0.001) and RV-FWLS (-18.9 ± 4 vs. -24.6 ± 5.12%, p < 0.001) values compared to the PE- patients. According to the ROC-curve analysis, RV-FWLS < 21% was the best cut-off with which to predict PE diagnosis in patients after SARS-CoV-2 pneumonia (sensitivity 74%, specificity 89%, area under the curve = 0.819, p < 0.001). According to the multivariate logistic regression model, RV-FWLS < 21% was independently associated with PE (HR 34.96, 95% CI:3.24-377.09, p = 0.003) and obesity (HR 10.34, 95% CI:1.05-101.68, p = 0.045). In conclusion, in recovered COVID-19 patients with a history of PE+, there is a persistence of subclinical RV dysfunction one year after the acute phase of the disease, detectable by a significant impairment in RV-GLS and RV-FWLS. A reduction in RV-FWLS of lower than 21% is independently associated with COVID-related PE.

Aerosol delivery through high-flow nasal therapy: Technical issues and clinical benefits.

High-flow nasal cannula (HFNC) therapy is an oxygen delivery method particularly used in patients affected by hypoxemic respiratory failure. In comparison with the conventional "low flow" oxygen delivery systems, it showed several important clinical benefits. The possibility to nebulize drugs via HFNC represents a desirable medical practice because it allows the administration of inhaled drugs, mostly bronchodilators, without the interruption or modification of the concomitant oxygen therapy. HFNC, by itself has shown to exert a small but significant bronchodilator effect and improves muco-ciliary clearance; thus, the nebulization of bronchodilators through the HFNC circuit may potentially increase their pharmacological activity. Several technical issues have been observed which include the type of the nebulizer that should be used, its position within the HFNC circuit, and the optimal gas flow rates to ensure an efficient drug delivery to the lungs both in "quiet" and "distressed" breathing patterns. The aim of this review has been to summarize the scientific evidence coming from "in vitro" studies and to discuss the results of "in vivo" studies performed in adult subjects, mainly affected by obstructive lung diseases. Most studies seem to indicate the vibrating mesh nebulizer as the most efficient type of nebulizer and suggest to place it preferentially upstream from the humidifier chamber. In a quite breathing patterns, the inhaled dose seems to increase with lower flow rates while in a "distressed" breathing pattern, the aerosol delivery is higher when gas flow was set below the patient's inspiratory flow, with a plateau effect seen when the gas flow reaches approximately 50% of the inspiratory flow. Although several studies have demonstrated that the percentage of the loaded dose nebulized via HFNC reaching the lungs is small, the bronchodilator effect of albuterol seems not to be impaired when compared to the conventional inhaled delivery methods. This is probably attributed to its pharmacological activity. Prospective and well-designed studies in different cohort of patients are needed to standardize and demonstrate the efficacy of the procedure.

Association between Renal Function at Admission and COVID-19 in-Hospital Mortality in Southern Italy: Findings from the Prospective Multicenter Italian COVOCA Study.

BACKGROUND: Evidence has shown a close association between COVID-19 infection and renal complications in both individuals with previously normal renal function and those with chronic kidney disease (CKD). METHODS: The aim of this study is to evaluate the in-hospital mortality of SARS-CoV-2 patients according to their clinical history of CKD or estimated glomerular filtration rate (eGFR). This is a prospective multicenter observational cohort study which involved adult patients (≥18 years old) who tested positive with SARS-CoV-2 infection and completed their hospitalization in the period between November 2020 and June 2021. RESULTS: 1246 patients were included in the study, with a mean age of 64 years (SD 14.6) and a median duration of hospitalization of 15 days (IQR 9-22 days). Cox's multivariable regression model revealed that mortality risk was strongly associated with the stage of renal impairment and the Kaplan-Meier survival analysis showed a progressive and statistically significant difference (p < 0.0001) in mortality according to the stage of CKD. CONCLUSION: This study further validates the association between CKD stage at admission and mortality in patients hospitalized for COVID-19. The risk stratification based on eGFR allows clinicians to identify the subjects with the highest risk of intra-hospital mortality despite the duration of hospitalization.

Evolution of the Clinical Profile and Outcomes of Unvaccinated Patients Affected by Critical COVID-19 Pneumonia from the Pre-Vaccination to the Post-Vaccination Waves in Italy.

The vaccination campaign and the new SARS-CoV-2 variants may have changed the clinical profile and outcomes of patients admitted to sub-intensive unit care. We conducted a retrospective study aimed to compare the clinical and radiological features of unvaccinated critical COVID-19 patients hospitalized during the last pandemic wave (December 2021-February 2022, No-Vax group) and before starting the vaccination campaign (March-December 2020, Pre-Vax group). The No-Vax group was also compared with vaccinated patients of the same pandemic wave (Vax group). With respect to the Pre-Vax group, the No-Vax group contained a higher percentage of smokers (p = 0.0007) and a lower prevalence of males (p = 0.0003). At admission, the No-Vax patients showed both a higher CT score of pneumonia and a worse severe respiratory failure (p < 0.0001). In the No-Vax group, a higher percentage of deaths occurred, though this was not significant. In comparison with the No-Vax group, the Vax patients were older (p = 0.0097), with a higher Charlson comorbidity index (p < 0.0001) and a significantly lower HRCT score (p = 0.0015). The percentage of deaths was not different between the two groups. The No-Vax patients showed a more severe disease in comparison with the Pre-Vax patients, and were younger and had fewer comorbidities than the Vax patients.

Three Month Follow-Up of Patients With COVID-19 Pneumonia Complicated by Pulmonary Embolism.

Background: Previous studies have demonstrated persistent dyspnoea and impairment of respiratory function in the follow-up of patients who have recovered from COVID-19 pneumonia. However, no studies have evaluated the clinical and functional consequences of COVID-19 pneumonia complicated by pulmonary embolism. Objective: The aim of our study was to assess the pulmonary function and exercise capacity in COVID-19 patients 3 months after recovery from pneumonia, either complicated or not by pulmonary embolism. Methods: This was a retrospective, single-centre, observational study involving 68 adult COVID-19 patients with a positive/negative clinical history of pulmonary embolism (PE) as a complication of COVID-19 pneumonia. Three months after recovery all patients underwent spirometry, diffusion capacity of the lungs for carbon monoxide (DLCO), and 6 minute walk test (6MWT). In addition, high-resolution computed tomography (HRCT) of the lung was carried out and CT-pulmonary angiography was conducted only in the PE+ subgroup. Patients with a previous diagnosis of PE or chronic lung diseases were excluded from the study. Results: Of the 68 patients included in the study, 24 had previous PE (PE+) and 44 did not (PE-). In comparison with the PE- subgroup, PE+ patients displayed a FVC% predicted significantly lower (87.71 ± 15.40 vs 98.7 ± 16.7, p = 0.009) and a significantly lower DLCO% predicted (p = 0.023). In addition, a higher percentage of patients were dyspnoeic on exercise, as documented by a mMRC score ≥1 (75% vs 54.3%, p < 0.001) and displayed a SpO2 <90% during 6MWT (37.5% vs 0%, p < 0.001). HRCT features suggestive of COVID-19 pneumonia resolution phase were present in both PE+ and PE- subjects without any significant difference (p = 0.24) and abnormalities at CT pulmonary angiography were detected in 57% of the PE+ subgroup. Conclusion: At the 3 month follow-up, the patients who recovered from COVID-19 pneumonia complicated by PE showed more dyspnoea and higher impairment of pulmonary function tests compared with those without PE.

Effectiveness of corticosteroids on chest high-resolution computed tomography features of COVID-19 pneumonia.

OBJECTIVE: The aim of our study was to assess the effect of a short-term treatment with low-moderate corticosteroid (CS) doses by both a quantitative and qualitative assessment of chest HRCT of COVID-19 pneumonia. METHODS: CORTICOVID is a single-center, cross-sectional, retrospective study involving severe/critical COVID-19 patients with mild/moderate ARDS. Lung total severity score was obtained according to Chung and colleagues. Moreover, the relative percentages of lung total severity score by ground glass opacities, consolidations, crazy paving, and linear bands were computed. Chest HRCT scores, P/F ratio, and laboratory parameters were evaluated before (pre-CS) and 7-10 days after (post-CS) methylprednisolone of 0.5-0.8 mg/kg/day. FINDINGS: A total of 34 severe/critical COVID-19 patients were included in the study, of which 17 received Standard of Care (SoC) and 17 CS therapy in add-on. CS treatment disclosed a significant decrease in HRCT total severity score [median = 6 (IQR: 5-7.5) versus 10 (IQR: 9-13) in SoC, p < 0.001], as well in single consolidations [median = 0.33 (IQR: 0-0.92) versus 6.73 (IQR: 2.49-8.03) in SoC, p < 0.001] and crazy paving scores [mean = 0.19 (SD = 0.53) versus 1.79 (SD = 2.71) in SoC, p = 0.010], along with a significant increase in linear bands [mean = 2.56 (SD = 1.65) versus 0.97 (SD = 1.30) in SoC, p = 0.006]. GGO score instead did not significantly differ at the end of treatment between the two groups. Most post-CS GGO, however, derived from previous consolidations and crazy paving [median = 1.5 (0.35-3.81) versus 2 (1.25-3.8) pre-CS; p = 0.579], while pre-CS GGO significantly decreased after methylprednisolone therapy [median = 0.66 (0.05-1.33) versus 1.5 (0.35-3.81) pre-CS; p = 0.004]. CS therapy further determined a significant improvement in P/F levels [median P/F = 310 (IQR: 235.5-370) versus 136 (IQR: 98.5-211.75) in SoC; p < 0.001], and a significant increase in white blood cells, lymphocytes, and neutrophils absolute values. CONCLUSION: The improvement of all chest HRCT findings further supports the role of CS adjunctive therapy in severe/critical COVID-19 pneumonia.

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.

Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence.

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab's therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

ACE Gene I/D Polymorphism and Acute Pulmonary Embolism in COVID19 Pneumonia: A Potential Predisposing Role.

Most recent studies have stressed a high risk of thromboembolism in patients with SARS-CoV-2 infection, particularly in those with severe COVID-19 pneumonia. Counterbalance between angiotensin-converting-enzyme (ACE) and ACE2 activities in COVID-19 disease may be crucially involved in the thrombo-inflammatory process. Currently, no study has investigated ACE I/D polymorphism involvement in COVID-19 disease complicated by pulmonary embolism, hence the aim of the present pilot study. This is a retrospective, single-center observational case-control study, conducted at the Sub-Intensive Care Unit of A.O.R.N. Ospedali dei Colli, Cotugno Hospital, Naples (Italy). We included 68 subjects with severe/critical COVID-19 pneumonia. COVID-19 patients were divided according to occurrence of PE (PE+, n = 25) or absence of thromboembolic complications (PE-, n = 43). Assessment of ACE I/D polymorphisms showed a statistically significant difference between PE+ and PE- patients (p = 0.029). Particularly, prevalence of D/D homozygous polymorphism was significantly higher in PE+ COVID-19 patients than in PE- (72 vs. 46.5%; p = 0.048), while heterozygote I/D polymorphism was significantly lower expressed in PE+ patients than in PE- (16 vs. 48.8%; p = 0.009). Computed tomographic pulmonary angiography showed predominantly mono/bilateral sub-segmental embolisms. In conclusion, our findings let us hypothesize a genetic susceptibility to thromboembolism in COVID-19 disease. ACE D/D polymorphism might represent a genetic risk factor, although studies on larger populations are needed.

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.