Dysregulation of glutamine/glutamate metabolism in COVID-19 patients: A metabolism study in African population and mini meta-analysis.

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; -log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs = 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17-3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14-4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20-0.44), and 0.44 (95% CI: 0.19-0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.

One-step synthesis of triethanolamine-capped Pt nanoparticle for colorimetric and electrochemiluminescent immunoassay of SARS-CoV spike proteins.

Platinum nanoparticles (PtNPs) have been attracted worldwide attention due to their versatile application potentials, especially in the catalyst and sensing fields. Herein, a facile synthetic method of triethanolamine (TEOA)-capped PtNPs (TEOA@PtNP) for electrochemiluminescent (ECL) and colorimetric immunoassay of SARS-CoV spike proteins (SARS-CoV S-protein, a target detection model) is developed. Monodisperse PtNPs with an average diameter of 2.2 nm are prepared by a one-step hydrothermal synthesis method using TEOA as a green reductant and stabilizer. TEOA@PtNPs can be used as a nanocarrier to combine with antigen by the high-affinity antibody, which leads to a remarkable inhibition of electron transfer efficiency and mass transfer processes. On the basis of its peroxidase-like activity and easy-biolabeling property, the TEOA@PtNP can be used to establish a colorimetric immunosensor of SARS-CoV S-protein thought catalyzing the reaction of H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB). Especially, the Ru(bpy)3 2+ ECL reaction is well-achieved with the TEOA@PtNPs due to their great conductivity and loading abundant TEOA co-reactants, resulting in an enhancing ECL signal in immunoassay of SARS-CoV S-protein. As a consequence, two proposed methods could achieve sensitive detection of SARS-CoV S-protein in wide ranges, the colorimetric and ECL detection limits were as low as 8.9 fg /mL and 4.2 fg /mL (S/N = 3), respectively. We believe that the proposed colorimetric and ECL immunosesors with high sensitivity, good reproducibility, and good stability will be a promising candidate for a broad spectrum of applications.

An early novel prognostic model for predicting 80-day survival of patients with COVID-19.

The outbreak of the novel coronavirus disease 2019 (COVID-19) has had an unprecedented impact worldwide, and it is of great significance to predict the prognosis of patients for guiding clinical management. This study aimed to construct a nomogram to predict the prognosis of COVID-19 patients. Clinical records and laboratory results were retrospectively reviewed for 331 patients with laboratory-confirmed COVID-19 from Huangshi Hospital of Traditional Chinese Medicine (TCM) (Infectious Disease Hospital) and Third Affiliated Hospital of Sun Yat-sen University. All COVID-19 patients were followed up for 80 days, and the primary outcome was defined as patient death. Cases were randomly divided into training (n=199) and validation (n=132) groups. Based on baseline data, we used statistically significant prognostic factors to construct a nomogram and assessed its performance. The patients were divided into Death (n=23) and Survival (n=308) groups. Analysis of clinical characteristics showed that these patients presented with fever (n=271, 81.9%), diarrhea (n=20, 6.0%) and had comorbidities (n=89, 26.9.0%). Multivariate Cox regression analysis showed that age, UREA and LDH were independent risk factors for predicting 80-day survival of COVID-19 patients. We constructed a qualitative nomogram with high C-indexes (0.933 and 0.894 in the training and validation groups, respectively). The calibration curve for 80-day survival showed optimal agreement between the predicted and actual outcomes. Decision curve analysis revealed the high clinical net benefit of the nomogram. Overall, our nomogram could effectively predict the 80-day survival of COVID-19 patients and hence assist in providing optimal treatment and decreasing mortality rates.

The role of selenium in severe fever with thrombocytopenia syndrome: an integrative analysis of surveillance data and clinical data.

OBJECTIVES: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). METHOD: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. RESULTS: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16). CONCLUSION: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

The Neutrophil-to-Lymphocyte Ratio is Associated with the Requirement and the Duration of Invasive Mechanical Ventilation in Acute Respiratory Distress Syndrome Patients: A Retrospective Study.

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality and most ARDS patients require ventilatory support. Applying appropriate ventilation strategies based on patients' individual situations has a direct impact upon patients' outcome. The neutrophil-to-lymphocyte ratio (NLR) has been shown to predict the early requirement of invasive mechanical ventilation (IMV) in patients with coronavirus disease 2019 (COVID-19). Our study aimed to investigate the relationship between baseline NLR and IMV in ARDS. Methods: A retrospective study was performed on patients who were diagnosed with ARDS using the Berlin definition and admitted to the First Affiliated Hospital of Soochow University from 2017 to 2022. Clinical data within 24 h after the ARDS diagnosis were collected from the medical record system. Based on the ventilation strategies during hospitalization, patients were divided into three groups and their clinical characteristics were compared. Furthermore, logistic regression analysis was used to screen the independent risk factors for IMV. STROBE checklist was used for this manuscript. Results: 520 ARDS patients were included and the median NLR value in IMV group was significantly higher than that of other groups (P < 0.001). NLR was significantly associated with the requirement of IMV in ARDS patients (OR, 1.042; 95% CI, 1.025-1.060; P < 0.001), other independent risk factors included PaO2/FiO2, Hb, lactate, and use of vasoactive drugs (all P < 0.05). Moreover, we found that the duration of IMV was longer in patients with high NLR (8[IQR, 3-13], 10[IQR, 6-16], respectively, P=0.025). Conclusions: Our results revealed that high baseline NLR level was significantly correlated with an increased risk of IMV in patients with ARDS. Furthermore, higher NLR was associated with prolonged duration of IMV in patients with ARDS.

Differential Influence of the COVID-19 Pandemic on Mechanical Thrombectomy and Bridging Therapy for Acute Ischemic Stroke.

Background: The coronavirus disease 2019 (COVID-19) pandemic is having a dramatic impact on acute stroke care. Its effects may accompany stroke care for a long time. We compared the treatment, short-term and long-term functional outcomes of patients with AIS from 2019 to 2020. Our objective was to evaluate the effect of COVID-19 epidemic on mechanical thrombectomy (MT) in patients in our hospital. Methods: We collected information on subjects treated with MT in 2019-2020, including age, sex, time from the onset to arterial sheath insertion, time from the onset to recanalization, the rate of lung infection and hemorrhagic transformation, modified Rankin scale (mRS), NHISS, and ASPECTS. Results: The number of patients with MT decreased significantly by 26.6% in 2020 (p = 0.025). The pretreatment ASPECTS score for 2020 was significantly higher than 2019 (p = 0.004). Besides, the patients were more likely to develop lung infection (65 vs. 54.1%, p = 0.042) and had a higher risk of hemorrhagic transformation (47.4% vs. 30.4%, p = 0.005) in 2019. The discharged mRS reflected the worse short-term functional prognosis of patients with MT in 2019 (66 vs. 44.9%, p = 0.046). In the subgroup analysis of bridging thrombolysis (BT), more patients with BT are expected to have a poor short-term functional prognosis in 2020, according to the discharged mRS (62.5 vs. 37.5%, p = 0.024). However, there was no difference in mRS at 180 days between the two groups (p = 0.094). Conclusion: For patients with MT, both short- and long-term functional outcomes were not significantly affected due to the mild condition of patients admitted to hospital in 2020. For patients with BT, the COVID-19 pandemic has prolonged the green channel time of stroke, leading to a poor short-term functional prognosis of patients with stroke in the pandemic period. There was no difference in the effectiveness of direct MT and BT during the COVID-19 pandemic.

Photosensitized Electrospun Nanofibrous Filters for Capturing and Killing Airborne Coronaviruses under Visible Light Irradiation.

To address the challenge of the airborne transmission of SARS-CoV-2, photosensitized electrospun nanofibrous membranes were fabricated to effectively capture and inactivate coronavirus aerosols. With an ultrafine fiber diameter (∼200 nm) and a small pore size (∼1.5 µm), optimized membranes caught 99.2% of the aerosols of the murine hepatitis virus A59 (MHV-A59), a coronavirus surrogate for SARS-CoV-2. In addition, rose bengal was used as the photosensitizer for membranes because of its excellent reactivity in generating virucidal singlet oxygen, and the membranes rapidly inactivated 97.1% of MHV-A59 in virus-laden droplets only after 15 min irradiation of simulated reading light. Singlet oxygen damaged the virus genome and impaired virus binding to host cells, which elucidated the mechanism of disinfection at a molecular level. Membrane robustness was also evaluated, and in general, the performance of virus filtration and disinfection was maintained in artificial saliva and for long-term use. Only sunlight exposure photobleached membranes, reduced singlet oxygen production, and compromised the performance of virus disinfection. In summary, photosensitized electrospun nanofibrous membranes have been developed to capture and kill airborne environmental pathogens under ambient conditions, and they hold promise for broad applications as personal protective equipment and indoor air filters.

Monocyte-to-lymphocyte ratio is associated with 28-day mortality in patients with acute respiratory distress syndrome: a retrospective study.

BACKGROUND: Systemic inflammation relates to the initiation and progression of acute respiratory distress syndrome (ARDS). Neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW)/albumin ratio have been reported to be predictive prognostic biomarkers in ARDS patients. However, the role of monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in a variety of diseases is rarely mentioned in ARDS. In this study, we explored the relationship between MLR and disease severity in ARDS patients and compared it with other indicators associated with 28-day mortality in patients with ARDS. METHODS: We retrospectively included 268 patients who fulfilled the Berlin definition of ARDS and were admitted to a single institute from 2016 to 2020. Clinical characteristics and experimental test data were collected from medical records within 24 h after the ARDS diagnosis. MLR, NLR, and RDW/albumin ratio levels were calculated. The primary clinical outcome was 28-day mortality. Logistic regression analysis was used to illustrate the relationship between indicators and 28-day mortality. Receiver operating characteristic (ROC) curve was used to evaluate the area under the curve (AUC), and propensity score matching (PSM) was employed to validate our findings. RESULTS: The median MLR values were higher for non-survivors than for survivors before and after matching (P<0.001, P=0.001, respectively). MLR values were significantly associated with 28-day mortality (OR 2.956; 95% CI 1.873-4.665; P<0.001). MLR and NLR indicators were combined for predictive efficacy analysis, and its AUC reached 0.750. There was a significant increase in 28-day mortality depending on the increasing MLR level: low MLR group 38 (20.4%), high MLR group 47 (57.3%) (P<0.001). CONCLUSIONS: Higher MLR values were associated with 28-day mortality in patients with ARDS. Further investigation is required to verify this relationship with prospectively collected data.

The impact of individual lifestyle and status on the acquisition of COVID-19: A case-Control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread to the world. Whether there is an association between lifestyle behaviors and the acquisition of COVID-19 remains unclear. METHODS: In this case-control study, we recruited 105 patients with SARS-CoV-2 infection as a case group from the Wuhan Tongji Hospital (Wuhan, China). For each case two control subjects were recruited. Participants were randomly selected from communities in Wuhan and matched for sex, age (± 2yrs), and pre-existing comorbidities (hypertension and diabetes). RESULTS: A total of 105 patients diagnosed with COVID-19 and 210 controls were included. Compared with control group, the case group had higher proportions of lack of sleep (30.5% vs. 14.8%, P = 0.001) and increased physical activities (56.2% vs. 32.9%, P < 0.001). And patients in the case group were more likely to have alopecia (28.6% vs. 10.0%, P < 0.001) than people from the control group. Overall, we found that lack of sleep [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 1.03-2.39)], physical activities (≥ 5 times a week) (adjusted OR 2.05, 95%CI 1.39-3.02) and alopecia (adjusted OR 1.73, 95%CI 1.13-2.66) were independent risk factors for COVID-19 infection. Conversely, low-dose alcohol intake (<100g alcohol per week), hand hygiene, and fruits intake (daily) were significantly associated with a decrease in morbidity. CONCLUSIONS: Individual lifestyle behaviors and health status can affect the occurrence of COVID-19.