The Dysregulation of the Monocyte-Dendritic Cell Interplay Is Associated with In-Hospital Mortality in COVID-19 Pneumonia.

Background: The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F; mean age ± SD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169+ monocytes, conventional CD1c+ and CD141+ (namely cDC2 and cDC1), and plasmacytoid CD303+ DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory-related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p < 0.0001). COVID-19 cases with absolute counts of CD169+ monocytes above the median value of 114.68/µL had significantly higher in-hospital mortality (HR 4.96; 95% CI: 1.42-17.27; p = 0.02). Interleukin (IL)-6 concentrations were significantly increased in COVID-19 patients (p < 0.0001 vs. controls), and negatively correlated with the absolute counts of circulating CD1c+ cDC2 (r = -0.29, p = 0.034) and CD303+ pDC (r = -0.29, p = 0.036) subsets. Viral genes were upregulated in patients with worse outcomes along with inflammatory mediators such as interleukin (IL)-1 beta, tumor necrosis-α (TNF-α) and the anticoagulant protein (PROS1). Conversely, surviving patients had upregulated genes related to inflammatory and anti-viral-related pathways along with the T cell membrane molecule CD4. Conclusions: Our results suggest that the dysregulated interplay between the different components of the MPS along with the imbalance between viral gene expression and host anti-viral immunity negatively impacts COVID-19 outcomes. Although the clinical scenario of COVID-19 has changed over time, a deepening of its pathogenesis remains a priority in clinical and experimental research.

Clinical correlates of circulating small dense low-density lipoproteins in acute infective endocarditis.

BACKGROUND AND AIM: Infective endocarditis (IE) is a complex thrombo-inflammatory disorder, the pathogenesis of which involves a multifaceted interplay between vascular damage and bacterial virulence factors. This study aimed to assess the prognostic role of small dense low-density lipoprotein (sdLDL) cholesterol in patients with IE and its correlation with various disease-related features. METHODS: A cohort of 198 patients with definite IE was included in this study. Clinical, laboratory, and echocardiographic parameters were meticulously analyzed, with a specific focus on comorbidities. sdLDL levels were measured using stored plasma samples obtained upon admission during the acute phase of the disease. RESULTS: The median level of sdLDL was 24 mg/dL [with an interquartile range of 17.9-35.2 mg/dL], and this value showed a statistically significant positive correlation with LDL/HDL cholesterol and triglycerides (p < 0.01 for all). Furthermore, a remarkable inverse correlation between C-reactive protein and D-dimer levels was observed (p < 0.0001). Univariate analysis revealed that patients with sdLDL levels ≤ 24 mg/dL had 2.75 times higher odds of in-hospital mortality (95% Confidence Interval:1.08-6.98, p = 0.031). In addition, nonsurvivors had significantly lower median sdLDL levels (19.7 vs. 26.0 mg/dL, p = 0.041). Lower sdLDL levels were also associated with embolic complications, larger vegetation size, and positive blood cultures for Staphylococci (p = 0.019, p = 0.022, and p < 0.001, respectively). CONCLUSIONS: Low circulating sdLDL levels in the acute phase of IE were significantly correlated with unfavorable clinical outcomes. These results suggest that the sdLDL level may serve as an important marker of disease severity in IE and may represent a link between vascular damage, embolic complications, and disease progression.

An observational study of a cohort of citizens receiving the AZD1222 vaccine against SARS-CoV-2.

In this retrospective study, a cohort of 67 subjects vaccinated with AZD1222 was retrospectively observed. Consistently with published findings, no serious adverse event was reported, and all adverse events reported (fever, muscle ache and/or pain in the site of injection) had resolved by day 8. Of note, some citizens were prescribed low-dose aspirin and even heparin for thrombosis prevention. We also found variations in laboratory test results (full blood count and chemistry) on day 1 compared with day 8. Physicians should be aware that no prevention therapy for thrombosis is currently recommended, given the very low incidence of this side effect. Additional studies are warranted to interpret our findings.