Clinical and baseline computed tomography features of patients infected with the B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2

PURPOSE: The purpose of this study was to investigate the clinical and baseline computed tomography (CT) features and their correlation in patients infected with the B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MATERIALS AND METHODS: Clinical and chest baseline CT data of patients infected with the Delta variant of SARS-CoV-2 from July to August 2021 were collected. First, the correlation between the clinical data and baseline CT results was analyzed according to CT positivity or negativity. Then, subgroup analysis was performed between different age distributions and clinical characteristics. Next, the CT characteristics and clinical data of all baseline CT-positive patients were collected, and the correlations between CT characteristics and age, vaccination status, and chronic disease were analyzed. Lesions in patients with baseline CT positivity were evaluated by semi-quantitative scoring to analyze the correlations between the semi-quantitative scores and vaccination status and age distribution. RESULTS: A total of 221 nucleic acid-positive patients with the SARS-CoV-2 Delta variant were included, of whom 107 patients were baseline CT positive and 114 were baseline CT negative. Baseline CT positivity was associated with age distribution, and baseline CT positivity was most common in patients aged >60 years (P < 0.001), but not with vaccination status or gender. The results of the subgroup analysis according to age distribution indicated that different age distribution subgroups had different vaccination statuses, and the majority of patients aged <18 years and >60 years were unvaccinated (90.5%, 19/21, and 57.3%, 63/110, respectively). In contrast, most patients aged 18–60 years had received two doses of the vaccine (61.1%, 55/90) (P < 0.001). Different age distribution subgroups had different clinical infection types. Asymptomatic and mild cases were most common in patients aged ≤60 years, and moderate and severe or critical cases were most common in patients aged >60 years. For baseline CT-positive patients, the extent of lung involvement was associated with age, vaccination status, and chronic disease. The number of involved lobes was higher in patients who were unvaccinated or who had received one injection, who were aged >60 years or had chronic disease. There was a statistical difference in CT semi-quantitative scores between the different age subgroups. Compared with patients aged < 60 years, patients aged >60 years had higher semi-quantitative scores (P < 0.001). However, there was no statistical difference between the different vaccination groups. CONCLUSIONS: Age had a large effect on baseline CT positivity, CT characteristics, and semi-quantitative CT scores in patients infected with the Delta variant.

Multi-omics and immune cells' profiling of COVID-19 patients for ICU admission prediction: in silico analysis and an integrated machine learning-based approach in the framework of Predictive, Preventive, and Personalized Medicine.

Background: Intensive care unit admission (ICUA) triage has been urgent need for solving the shortage of ICU beds, during the coronavirus disease 2019 (COVID-19) surge. In silico analysis and integrated machine learning (ML) approach, based on multi-omics and immune cells (ICs) profiling, might provide solutions for this issue in the framework of predictive, preventive, and personalized medicine (PPPM). Methods: Multi-omics was used to screen the synchronous differentially expressed protein-coding genes (SDEpcGs), and an integrated ML approach to develop and validate a nomogram for prediction of ICUA. Finally, the independent risk factor (IRF) with ICs profiling of the ICUA was identified. Results: Colony-stimulating factor 1 receptor (CSF1R) and peptidase inhibitor 16 (PI16) were identified as SDEpcGs, and each fold change (FCij) of CSF1R and PI16 was selected to develop and validate a nomogram to predict ICUA. The area under curve (AUC) of the nomogram was 0.872 (95% confidence interval (CI): 0.707 to 0.950) on the training set, and 0.822 (95% CI: 0.659 to 0.917) on the testing set. CSF1R was identified as an IRF of ICUA, expressed in and positively correlated with monocytes which had a lower fraction in COVID-19 ICU patients. Conclusion: The nomogram and monocytes could provide added value to ICUA prediction and targeted prevention, which are cost-effective platform for personalized medicine of COVID-19 patients. The log2fold change (log2FC) of the fraction of monocytes could be monitored simply and economically in primary care, and the nomogram offered an accurate prediction for secondary care in the framework of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00317-5.

Macrophage ferroportin serves as a therapeutic target against bacteria-induced acute lung injury by promoting barrier restoration.

Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were characterized by increased expression of ferroportin (FPN). Specifically deleting FPN in myeloid cells conferred significant resistance to bacterial infection with improved survival by decreasing extracellular bacterial growth and preserving pulmonary barrier integrity in mice. Mechanistically, macrophage FPN deficiency not only limited the availability of iron to bacteria, but also promoted tissue restoration via growth factor amphiregulin, which is regulated by cellular iron-activated Yes-associated protein signaling. Furthermore, pharmacological treatment with C-Hep, the self-assembled N-terminally cholesterylated minihepcidin that functions in the degradation of macrophage FPN, protected against bacteria-induced lung injury. Therefore, therapeutic strategies targeting the hepcidin-FPN axis in macrophages may be promising for the clinical treatment of acute lung injury.

Tracheostomy timing and clinical outcomes in ventilated COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The association of tracheostomy timing and clinical outcomes in ventilated COVID-19 patients remains controversial. We performed a meta-analysis to evaluate the impact of early tracheostomy compared to late tracheostomy on COVID-19 patients' outcomes. METHODS: We searched Medline, Embase, Cochrane, and Scopus database, along with medRxiv, bioRxiv, and Research Square, from December 1, 2019, to August 24, 2021. Early tracheostomy was defined as a tracheostomy conducted 14 days or less after initiation of invasive mechanical ventilation (IMV). Late tracheostomy was any time thereafter. Duration of IMV, duration of ICU stay, and overall mortality were the primary outcomes of the meta-analysis. Pooled odds ratios (OR) or the mean differences (MD) with 95%CIs were calculated using a random-effects model. RESULTS: Fourteen studies with a cumulative 2371 tracheostomized COVID-19 patients were included in this review. Early tracheostomy was associated with significant reductions in duration of IMV (2098 patients; MD - 9.08 days, 95% CI - 10.91 to - 7.26 days, p < 0.01) and duration of ICU stay (1224 patients; MD - 9.41 days, 95% CI - 12.36 to - 6.46 days, p < 0.01). Mortality was reported for 2343 patients and was comparable between groups (OR 1.09, 95% CI 0.79-1.51, p = 0.59). CONCLUSIONS: The results of this meta-analysis suggest that, compared with late tracheostomy, early tracheostomy in COVID-19 patients was associated with shorter duration of IMV and ICU stay without modifying the mortality rate. These findings may have important implications to improve ICU availability during the COVID-19 pandemic. Trial registration The protocol was registered at INPLASY (INPLASY202180088).

Prognostic Value of Coronary CT Angiography-Derived Fractional Flow Reserve in Non-obstructive Coronary Artery Disease: A Prospective Multicenter Observational Study

Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Myocardial ischemia may occur in patients with normal or non-obstructive CAD on invasive coronary angiography (ICA). The comprehensive evaluation of coronary CT angiography (CCTA) integrated with fractional flow reserve derived from CCTA (CT-FFR) to CAD may be essential to improve the outcomes of patients with non-obstructive CAD. China CT-FFR Study-2 (ChiCTR2000031410) is a large-scale prospective, observational study in 29 medical centers in China. The primary purpose is to uncover the relationship between the CCTA findings (including CT-FFR) and the outcome of patients with non-obstructive CAD. At least 10,000 patients with non-obstructive CAD but without previous revascularization will be enrolled. A 5-year follow-up will be performed. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarct, unplanned revascularization, and hospitalization for unstable angina. Clinical characteristics, laboratory and imaging examination results will be collected to analyze their prognostic value.

A commentary of “Type I Interferon Deficiency Can Lead to Severe COVID-19” in 10 remarkable discoveries from 2020 in Nature

In two articles published in Science online in September 2020, Zhang et al [1]. and Bastard et al [2]. elucidated a key factor in the progression to severe COVID-19;namely, a deficiency in interferon, especially type I interferon (IFN I). This deficiency might be caused by diverse reasons such as genetic mutations of genes encoding key antiviral signaling molecules, or the ‘neutralization’ of IFN I by endogenous antibodies. How does IFN I deficiency cause severe, life-threatening COVID-19? The most straightforward explanation is that such deficiency allows uncontrolled virus replication and spread. IFN I deficiency may also have other impacts on immune system function. Individuals with mutations in the IFN-I-induced signaling pathways may benefit from interferon therapies. In addition, individuals with neutralizing antibodies against IFN-α and IFN-ω may also benefit from other types of interferons provided in the therapy, such as IFN-β and IFN-λ.①

A Comparison of CT Manifestations Between Coronavirus Disease 2019 (COVID-19) and Other Types of Viral Pneumonia.

BACKGROUND: Though imaging manifestations of COVID-19 and other types of viral pneumonia are similar, their clinical treatment methods differ. Accurate, non-invasive diagnostic methods using CT imaging can help develop an optimal therapeutic regimen for both conditions. OBJECTIVE: To compare the initial CT imaging features in COVID-19 with those in other types of viral pneumonia. METHODS: Clinical and imaging data of 51 patients with COVID-19 and 69 with other types of viral pneumonia were retrospectively studied. All significant imaging features (Youden index >0.3) were included for constituting the combined criteria for COVID-19 diagnosis, composed of two or more imaging features with a parallel model. McNemar's chi-square test or Fisher's exact test was used to compare the validity indices (sensitivity and specificity) among various criteria. RESULTS: Ground glass opacities (GGO) dominated density, peripheral distribution, unilateral lung, clear margin of lesion, rounded morphology, long axis parallel to the pleura, vascular thickening, and crazy-paving pattern were more common in COVID-19 (p <0.05). Consolidation-dominated density, both central and peripheral distributions, bilateral lung, indistinct margin of lesion, tree-inbud pattern, mediastinal or hilar lymphadenectasis, pleural effusion, and pleural thickening were more common in other types of viral pneumonia (p < 0.05). GGO-dominated density or long axis parallel to the pleura (with the highest sensitivity), and GGO-dominated density or long axis parallel to the pleura or vascular thickening (with the highest specificity) are well combined criteria of COVID-19. CONCLUSION: The initial CT imaging features are helpful for the differential diagnosis of COVID-19 and other types of viral pneumonia.

Application of Chinese Medicine in the Management of Critical Conditions: A Review on Sepsis.

Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance, controversial of glucocorticoids use, prolonged duration of ICU care and the subsequent high cost of the treatment. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) in sepsis management. The TCM application emphasizes use of herbal formulation to balance immune responses to infection, which include clearing heat and toxin, promoting blood circulation and removing its stasis, enhancing gastrointestinal function, and strengthening body resistance. In this paper, we will provide an overview of the current status of Chinese herbal formulations, single herbs, and isolated compounds, as an add-on therapy to the standard Western treatment in the sepsis management. With the current trajectory of worldwide pandemic eruption of newly identified Coronavirus Disease-2019 (COVID-19), the adjuvant TCM therapy can be used in the ICU to treat critically ill patients infected with the novel coronavirus.

The poor prognosis and influencing factors of high D-dimer levels for COVID-19 patients.

To explore the value, and influencing factors, of D-dimer on the prognosis of patients with COVID-19. A total of 1,114 patients with confirmed COVID-19 who were admitted to three designated COVID-19 hospitals in Wuhan, China from January 18, 2020, to March 24, 2020, were included in this study. We examined the relationship between peripheral blood levels of D-dimer, and clinical classification and prognosis, as well as its related influencing factors. D-dimer levels were found to be related to the clinical classification and the prognosis of clinical outcome. D-dimer levels were more likely to be abnormal in severely and critically ill patients compared with mild and ordinary cases, while D-dimer levels of patients who had died were significantly higher than those of surviving patients according to the results of the first and last lab tests. The results from ROC analyses for mortality risk showed that the AUCs of D-dimer were 0.909, YI was 0.765 at the last lab test, and a D-dimer value of 2.025 mg/L was regarded to be the optimal probability cutoff for a prognosis of death. In addition, we found that patients with advanced age, male gender, dyspnea symptoms, and some underlying diseases have a higher D-dimer value (p < 0.05). In short, D-dimer is related to the clinical classification and can be used to evaluate the prognosis of COVID-19 patients. The D-dimer value of 2.025 mg/L was the optimal probability cutoff for judging an outcome of death. Advanced age, male gender, dyspnea symptoms, and some underlying diseases are influencing factors for D-dimer levels, which impacts the prognosis of patients.