Outcomes of Extremely Prolonged (> 50 d) Venovenous Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: There has been a sustained increase in the utilization of venovenous extracorporeal membrane oxygenation (ECMO) over the last decade, further exacerbated by the COVID-19 pandemic. We set out to describe our institutional experience with extremely prolonged (> 50 d) venovenous ECMO support for recovery or bridge to lung transplant candidacy in patients with acute respiratory failure. DESIGN: Retrospective cohort study. SETTING: A large tertiary urban care center. PATIENTS: Patients 18 years or older receiving venovenous ECMO support for greater than 50 days, with initial cannulation between January 2018 and January 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty patients were placed on venovenous ECMO during the study period. Of these, 12 received prolonged (> 50 d) venovenous ECMO support. Eleven patients (92%) suffered from adult respiratory distress syndrome (ARDS) secondary to COVID-19, while one patient with prior bilateral lung transplant suffered from ARDS secondary to bacterial pneumonia. The median age of patients was 39 years (interquartile range [IQR], 35-51 yr). The median duration of venovenous ECMO support was 94 days (IQR, 70-128 d), with a maximum of 180 days. Median time from intubation to cannulation was 5 days (IQR, 2-14 d). Nine patients (75%) were successfully mobilized while on venovenous ECMO support. Successful weaning of venovenous ECMO support occurred in eight patients (67%); 6 (50%) were bridged to lung transplantation and 2 (17%) were bridged to recovery. Of those successfully weaned, seven patients (88%) were discharged from the hospital. All seven patients discharged from the hospital were alive 6 months post-decannulation; 83% (5/6) with sufficient follow-up time were alive 1-year after decannulation. CONCLUSIONS: Our experience suggests that extremely prolonged venovenous ECMO support to allow native lung recovery or optimization for lung transplantation may be a feasible strategy in select critically ill patients, further supporting the expanded utilization of venovenous ECMO for refractory respiratory failure.

Long-term variations and potency of neutralizing antibodies against Omicron subvariants after CoronaVac-inactivated booster: A 7-month follow-up study.

The long-term protective efficacy of neutralizing antibodies (Nabs) against Omicron subvariants after inactivated booster vaccines remains elusive. During the follow-up study, 54 healthy volunteers aged 20-31 years received inactivated CoronaVac booster vaccinations and were monitored for 221 days. The dynamic efficacy and durability of Nab against Omicron subvariants BA.1, BA.2, BA.2.12.2, and BA4/5 were assessed using a pseudotyped virus neutralization assay at up to nine time points post immunization. The antibody response against Omicron subvariants was substantially weaker than D614G, with BA.4/5 being the least responsive. The geometric mean titer (GMT) of Nab against Omicron subvariants BA.1, BA.2, BA.2.12.1, and BA.4/5 was 2.2-, 1.7-, 1.8-, and 2.2-fold lower than that against D614G (ps < 0.0001). The gap in Nab response between Omicron subvariants was pronounced during the 2 weeks-2 months following booster vaccination (ps < 0.05). Seven months post booster, the antibody potency against D614G was maintained at 100% (50% for Nab titers ≥ 100 50% inhibitory dilution [EC50 ]), whereas at 77.3% for BA.1, 90.9% for BA.2, 86.4% for BA.2.12.1, and 86.4% for BA.4/5 (almost 20% for Nab titers ≥ 100 EC50 ). Despite the inevitable immune escape, Omicron subvariants maintained sustained and measurable antibody potency post-booster vaccination during long-term monitoring, which could help optimize immunization strategies.

Dynamic Emergency Transit Forecasting with IoT Sequential Data

Medical emergency transit counts minutes as real human lives. It is important to plan emergency transport routes according to real-time traffic flow status which leads to the the essential requirement of correct dynamic traffic prediction. Many Internet of Things (IoT) devices have been employed to assist emergency transit. Dynamic traffic flow patterns can be better predicted using data given by those devices. In small cities, however, the data are sent into separated management offices or just saved inside edge devices due to system compatibility or the cost of mobile network to computer centres. This condition leads to small and local datasets. Making full use of small local data to conduct prediction is one way to solve local emergency planning problems. In this work, we design a dynamic graph structure to work with Graph Neural Network (GNN) algorithm to forecast traffic flow levels considering this scenario. The proposed graph considers both geographical and time information with the potential to grow within a local mobile communication network. The commonly used Extreme Gradient Boosting (XGBoost) is included in the comparison. Experimental results show that our new design provides high prediction efficiency and accuracy.

The Geography of Information Acquisition

Using detailed data on company visits by Chinese mutual funds, we provide direct evidence of mutual fund information acquisition activities and the consequent informational advantages mutual funds establish in local firms. Mutual funds are more likely to visit local and nearby firms both in and outside of their portfolios, but the ease of travel between fund and firm locations can substantially alleviate geographic distance constraints. Company visits by mutual funds are strongly associated with both fund trading activities and fund trading performance. Our results show that geographic constraints and costly information acquisition amplify information asymmetry in financial markets.

Patient and Clinical Factors at Admission Affect the Levels of Neutralizing Antibodies Six Months after Recovering from COVID-19.

The rate of decline in the levels of neutralizing antibodies (NAbs) greatly varies among patients who recover from Coronavirus disease 2019 (COVID-19). However, little is known about factors associated with this phenomenon. The objective of this study is to investigate early factors at admission that can influence long-term NAb levels in patients who recovered from COVID-19. A total of 306 individuals who recovered from COVID-19 at the Tongji Hospital, Wuhan, China, were included in this study. The patients were classified into two groups with high (NAbhigh, n = 153) and low (NAblow, n = 153) levels of NAb, respectively based on the median NAb levels six months after discharge. The majority (300/306, 98.0%) of the COVID-19 convalescents had detected NAbs. The median NAb concentration was 63.1 (34.7, 108.9) AU/mL. Compared with the NAblow group, a larger proportion of the NAbhigh group received corticosteroids (38.8% vs. 22.4%, p = 0.002) and IVIG therapy (26.5% vs. 16.3%, p = 0.033), and presented with diabetes comorbidity (25.2% vs. 12.2%, p = 0.004); high blood urea (median (IQR): 4.8 (3.7, 6.1) vs. 3.9 (3.5, 5.4) mmol/L; p = 0.017); CRP (31.6 (4.0, 93.7) vs. 16.3 (2.7, 51.4) mg/L; p = 0.027); PCT (0.08 (0.05, 0.17) vs. 0.05 (0.03, 0.09) ng/mL; p = 0.001); SF (838.5 (378.2, 1533.4) vs. 478.5 (222.0, 1133.4) µg/L; p = 0.035); and fibrinogen (5.1 (3.8, 6.4) vs. 4.5 (3.5, 5.7) g/L; p = 0.014) levels, but low SpO2 levels (96.0 (92.0, 98.0) vs. 97.0 (94.0, 98.0)%; p = 0.009). The predictive model based on Gaussian mixture models, displayed an average accuracy of 0.7117 in one of the 8191 formulas, and ROC analysis showed an AUC value of 0.715 (0.657-0.772), and specificity and sensitivity were 72.5% and 67.3%, respectively. In conclusion, we found that several factors at admission can contribute to the high level of NAbs in patients after discharge, and constructed a predictive model for long-term NAb levels, which can provide guidance for clinical treatment and monitoring.

Metabolic Reprogramming in COVID-19.

Plenty of research has revealed virus induced alternations in metabolic pathways, which is known as metabolic reprogramming. Studies focusing on COVID-19 have uncovered significant changes in metabolism, resulting in the perspective that COVID-19 is a metabolic disease. Reprogramming of amino acid, glucose, cholesterol and fatty acid is distinctive characteristic of COVID-19 infection. These metabolic changes in COVID-19 have a critical role not only in producing energy and virus constituent elements, but also in regulating immune response, offering new insights into COVID-19 pathophysiology. Remarkably, metabolic reprogramming provides great opportunities for developing novel biomarkers and therapeutic agents for COVID-19 infection. Such novel agents are expected to be effective adjuvant therapies. In this review, we integrate present studies about major metabolic reprogramming in COVID-19, as well as the possibility of targeting reprogrammed metabolism to combat virus infection.

Psychometric Properties of the Chinese Version of the Primary Care Post-Traumatic Stress Disorder Screen-5 for Medical Staff Exposed to the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic may increase the development of psychiatric disorders, such as posttraumatic stress disorder (PTSD) among medical staff. A brief validated screening tool is essential for the early diagnosis of PTSD. The purpose of the present study was to evaluate the validation of a Chinese version of the Primary Care-PTSD-5 (C-PC-PTSD-5) and determine an appropriate cutoff score with optimal sensitivity and specificity for medical staff in China during the COVID-19 pandemic. PARTICIPANTS AND METHODS: An online cross-sectional survey was conducted on medical staff (n = 1104) from 17 medical institutions in Shanghai. Questionnaires comprising general information, medical-related traumatic event experiences, the PTSD Checklist (PCL-5), and C-PC-PTSD-5 were distributed to participants using the online Questionnaire Star electronic system. Internal consistency, convergent validity, and test-retest reliability were calculated. Receiver operating characteristic (ROC) analysis was performed to determine diagnostic accuracy and the optimal cutoff score of the C-PC-PTSD-5 for medical staff. RESULTS: We included 1062 valid questionnaires for the analysis. Data of 838 traumatic experiences were analyzed. Internal consistency of the C-PC-PTSD-5 was satisfied (Cronbach's α = 0.756). The total score of the C-PC-PTSD-5 showed good test-retest reliability (r = 0.746). We found a strong correlation between the C-PC-PTSD-5 score and PCL-5 total score (r = 0.669, p < 0.001), which indicated good convergent validity. The ROC analysis showed an area under the curve of 0.81 ± 0.016. A cutoff score of 2 provided optimal sensitivity and specificity for the C-PC-PTSD-5 (sensitivity = 0.632, specificity = 0.871, Youden index = 0.503, and overall efficiency = 0.768). CONCLUSION: Our results indicated that the C-PC-PTSD-5 can be employed as a brief and efficient screening instrument for medical staff exposed to the COVID-19 pandemic. A score of 2 was identified as the optimal threshold for probable clinical PTSD symptoms.

Colloidal gold immunochromatographic assay (GICA) is an effective screening method for identifying detectable anti-SARS-CoV-2 neutralizing antibodies.

INTRODUCTION: A large number of COVID-19 patients are in recovery, and millions of people are vaccinated for COVID-19 globally. This calls for a rapid screening strategy of SARS-CoV-2 protective antibodies, generated in rehabilitated and vaccinated populations. METHODS: Serum samples collected over a follow-up period of six months from 306 COVID-19 cases discharged from Wuhan Tongji Hospital were analyzed. Anti-S Abs were detected by colloidal gold immunochromatographic assay (GICA), and neutralizing antibodies (nAbs) were detected by chemiluminescent microparticle immunoassay (CMIA). RESULTS: Most COVID-19 survivors tested positive for anti-S Abs (83.7%) and nAbs (98.0%) 6 months after being discharged from the hospital, and the levels of anti-S Abs in the blood were highly positively correlated with nAbs (r = 0.652, P < 0.0001). The positivity rate of nAbs for patients with anti-S Abs positive was 100%. CONCLUSIONS: There is a good agreement between anti-S Abs detected by GICA and nAbs detected by CMIA. It indicates that anti-S Abs detected by GICA may be used as a cheaper screening strategy for detectable SARS-CoV-2 nAbs in COVID-19 convalescent individuals.

A network pharmacology based approach for predicting active ingredients and potential mechanism of Lianhuaqingwen capsule in treating COVID-19.

The outbreak of severe respiratory disease caused by SARS-CoV-2 has led to millions of infections and raised global health concerns. Lianhuaqingwen capsule (LHQW-C), a traditional Chinese medicine (TCM) formula widely used for respiratory diseases, shows therapeutic efficacy in the application of coronavirus disease 2019 (COVID-19). However, the active ingredients, drug targets, and the therapeutic mechanisms of LHQW-C in treating COVID-19 are poorly understood. In this study, an integrating network pharmacology approach including pharmacokinetic screening, target prediction (targets of the host and targets from the SARS-CoV-2), network analysis, GO enrichment analysis, KEGG pathway enrichment analysis, and virtual docking were conducted. Finally, 158 active ingredients in LHQW-C were screen out, and 49 targets were predicted. GO function analysis revealed that these targets were associated with inflammatory response, oxidative stress reaction, and other biological processes. KEGG enrichment analysis indicated that the targets of LHQW-C were highly enriched to several immune response-related and inflammation-related pathways, including the IL-17 signaling pathway, TNF signaling pathway, NF-kappa B signaling pathway, and Th17 cell differentiation. Moreover, four key components (quercetin, luteolin, wogonin, and kaempferol) showed a high binding affinity with SARS-CoV-2 3-chymotrypsin-like protease (3CL pro). The study indicates that some anti-inflammatory ingredients in LHQW-C probably modulate the inflammatory response in severely ill patients with COVID-19.

Cardiac Troponin I association with critical illness and death risk in 726 seriously ill COVID-19 patients: A retrospective cohort study.

Background: For coronavirus disease 2019 (COVID-19), early identification of patients with serious symptoms at risk of critical illness and death is important for personalized treatment and balancing medical resources. Methods: Demographics, clinical characteristics, and laboratory tests data from 726 patients with serious COVID-19 at Tongji Hospital (Wuhan, China) were analyzed. Patients were classified into critical group (n = 174) and severe group (n= 552), the critical group was sub-divided into survivors (n = 47) and non-survivors (n = 127). Results: Multivariable analyses revealed the risk factors associated with critical illness in serious patients were: Advanced age, high respiratory rate (RR), high lactate dehydrogenase (LDH) level, high hypersensitive cardiac troponin I (hs-cTnI) level, and thrombocytopenia on admission. High hs-cTnI level was the independent risk factor of mortality among critically ill patients in the unadjusted and adjusted models. ROC curves demonstrated that hs-cTnI and LDH were predictive factors for critical illness in patients with serious COVID-19 whereas procalcitonin and D-Dimer with hs-cTnI and LDH were predictive parameters in mortality risk. Conclusions: Advanced age, high RR, LDH, hs-cTnI, and thrombocytopenia, constitute risk factors for critical illness among patients with serious COVID-19, and the hs-cTnI level helps predict fatal outcomes in critically ill patients.

Predictive indicators of severe COVID-19 independent of comorbidities and advanced age: a nested case-control study.

To determine what exacerbate severity of the COVID-19 among patients without comorbidities and advanced age and investigate potential clinical indicators for early surveillance, we adopted a nested case-control study, design in which severe cases (case group, n = 67) and moderate cases (control group, n = 67) of patients diagnosed with COVID-19 without comorbidities, with ages ranging from 18 to 50 years who admitted to Wuhan Tongji Hospital were matched based on age, sex and BMI. Demographic and clinical characteristics, and risk factors associated with severe symptoms were analysed. Percutaneous oxygen saturation (SpO2), lymphocyte counts, C-reactive protein (CRP) and IL-10 were found closely associated with severe COVID-19. The adjusted multivariable logistic regression analyses revealed that the independent risk factors associated with severe COVID-19 were CRP (OR 2.037, 95% CI 1.078-3.847, P = 0.028), SpO2 (OR 1.639, 95% CI 0.943-2.850, P = 0.080) and lymphocyte (OR 1.530, 95% CI 0.850-2.723, P = 0.148), whereas the changes exhibited by indicators influenced incidence of disease severity. Males exhibited higher levels of indicators associated with inflammation, myocardial injury and kidney injury than the females. This study reveals that increased CRP levels and decreased SpO2 and lymphocyte counts could serve as potential indicators of severe COVID-19, independent of comorbidities, advanced age and sex. Males could at higher risk of developing severe symptoms of COVID-19 than females.

Structure of human steroid 5α-reductase 2 with anti-androgen drug finasteride.

Human steroid 5α-reductase 2 (SRD5α2) as a critical integral membrane enzyme in steroid metabolism catalyzes testosterone to dihydrotestosterone. Mutations on its gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride as SRD5α2 inhibitors are widely used anti-androgen drugs for benign prostate hyperplasia, which have recently been indicated in the treatment of COVID-19. The molecular mechanisms underlying enzyme catalysis and inhibition remained elusive for SRD5α2 and other eukaryotic integral membrane steroid reductases due to a lack of structural information. Here, we report a crystal structure of human SRD5α2 at 2.8 Å revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the membrane. Structural analysis together with computational and mutagenesis studies reveals molecular mechanisms for the 5α-reduction of testosterone and the finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region regulating the NADPH/NADP + exchange. Mapping disease-causing mutations of SRD5α2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and will facilitate drug development.