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1.
BMC Medical Research Methodology ; 23(1):25, 2023.
Article in English | MEDLINE | ID: covidwho-2214531

ABSTRACT

BACKGROUND: Numerous clinical trials have been initiated to find effective treatments for COVID-19. These trials have often been initiated in regions where the pandemic has already peaked. Consequently, achieving full enrollment in a single trial might require additional COVID-19 surges in the same location over several years. This has inspired us to pool individual patient data (IPD) from ongoing, paused, prematurely-terminated, or completed randomized controlled trials (RCTs) in real-time, to find an effective treatment as quickly as possible in light of the pandemic crisis. However, pooling across trials introduces enormous uncertainties in study design (e.g., the number of RCTs and sample sizes might be unknown in advance). We sought to develop a versatile treatment efficacy assessment model that accounts for these uncertainties while allowing for continuous monitoring throughout the study using Bayesian monitoring techniques.

2.
Infectious Diseases and Immunity ; 1(1):28-35, 2021.
Article in English | Scopus | ID: covidwho-2212958

ABSTRACT

Background:Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces.Methods:In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality.Results:The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than10 × 109/L, neutrophil count of more than 7 × 109/L, lymphocyte count of less than 0.8 × 109/L, platelet count of less than 100 × 109/L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively.Conclusions:We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions. © 2021 The Chinese Medical Association, Published by Wolters Kluwer Health, Inc.

3.
Cambridge Journal of Regions Economy and Society ; 2022.
Article in English | Web of Science | ID: covidwho-2188622

ABSTRACT

Through a case study of Kunshan, China, this paper shows how a local state utilised place-based leadership to enhance regional economic resilience under the COVID-19 pandemic crisis. It unpacks how Kunshan effectively mitigated early economic disturbances induced by the COVID-19 pandemic, by two ways of leadership actions, namely, enacting jurisdictional power (that is formal leadership), and mobilising wide official and interpersonal networks (that is network leadership). Four specific local-state-led adaptive resilience processes or strategies are identified: stabilising labour supply, mitigating supply-chain disruptions, alleviating financial strains and reconfiguring market orientations. Through these proactive endeavours, the local state played an enabling role in aligning diverse stakeholders and resources across places, scales and sectors, thereby allaying economic shocks and enhancing regional economic resilience. This study contributes to the resilience literature by developing an agency-centric perspective to understanding regional economic resilience during the COVID-19 pandemic.

4.
Frontiers in Public Health ; 10, 2022.
Article in English | Web of Science | ID: covidwho-2163193

ABSTRACT

IntroductionAcute kidney injury (AKI) is a prevalent complication of coronavirus disease 2019 (COVID-19) and is closely linked with a poorer prognosis. The aim of this study was to develop and validate an easy-to-use and accurate early prediction model for AKI in hospitalized COVID-19 patients. MethodsData from 480 COVID-19-positive patients (336 in the training set and 144 in the validation set) were obtained from the public database of the Cancer Imaging Archive (TCIA). The least absolute shrinkage and selection operator (LASSO) regression method and multivariate logistic regression were used to screen potential predictive factors to construct the prediction nomogram. Receiver operating curves (ROC), calibration curves, as well as decision curve analysis (DCA) were adopted to assess the effectiveness of the nomogram. The prognostic value of the nomogram was also examined. ResultsA predictive nomogram for AKI was developed based on arterial oxygen saturation, procalcitonin, C-reactive protein, glomerular filtration rate, and the history of coronary artery disease. In the training set, the nomogram produced an AUC of 0.831 (95% confidence interval [CI]: 0.774-0.889) with a sensitivity of 85.2% and a specificity of 69.9%. In the validation set, the nomogram produced an AUC of 0.810 (95% CI: 0.737-0.871) with a sensitivity of 77.4% and a specificity of 78.8%. The calibration curve shows that the nomogram exhibited excellent calibration and fit in both the training and validation sets. DCA suggested that the nomogram has promising clinical effectiveness. In addition, the median length of stay (m-LS) for patients in the high-risk group for AKI (risk score >= 0.122) was 14.0 days (95% CI: 11.3-16.7 days), which was significantly longer than 8.0 days (95% CI: 7.1-8.9 days) for patients in the low-risk group (risk score <0.122) (hazard ratio (HR): 1.98, 95% CI: 1.55-2.53, p < 0.001). Moreover, the mortality rate was also significantly higher in the high-risk group than that in the low-risk group (20.6 vs. 2.9%, odd ratio (OR):8.61, 95%CI: 3.45-21.52). ConclusionsThe newly constructed nomogram model could accurately identify potential COVID-19 patients who may experience AKI during hospitalization at the very beginning of their admission and may be useful for informing clinical prognosis.

5.
J Coll Physicians Surg Pak ; 32(12):1637-1639, 2022.
Article in English | PubMed | ID: covidwho-2156107

ABSTRACT

The objective of the study was to investigate whether the peripheral lymphocyte count was independently negative association with viral clearance time of SARS-CoV-2 in Chinese patients with COVID-19. Total 202 patients were chosen for the last data analysis. The patients' mean age was 41.39±12.47 years. Male was accounted for 48.51% and female was 51.49% respectively. The average viral clearance time was 19.40±9.03 days. Adjusted linear regression result showed peripheral lymphocyte count was associated with viral clearance time negatively after adjusting confounders (β, -2.79;95% CI, -5.21 to -0.36). The trend of peripheral lymphocyte count treated as a categorical variable in linear regression was also consistent with the result when peripheral lymphocyte count was treated as a continuous variable. There was a negative association between peripheral lymphocyte count and viral clearance time of SARS-CoV-2 in Chinese patients with COVID-19. Key Words: Peripheral lymphocyte count, Viral clearance, COVID-19.

6.
Journal of Virology ; : e0124522, 2022.
Article in English | MEDLINE | ID: covidwho-2152892

ABSTRACT

The global spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuously emerging new variants underscore an urgent need for effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). Here, we screened several FDA-approved amphiphilic drugs and determined that sertraline (SRT) exhibits potent antiviral activity against infection of SARS-CoV-2 pseudovirus (PsV) and authentic virus in vitro. It effectively inhibits SARS-CoV-2 spike (S)-mediated cell-cell fusion. SRT targets the early stage of viral entry. It can bind to the S1 subunit of the S protein, especially the receptor binding domain (RBD), thus blocking S-hACE2 interaction and interfering with the proteolysis process of S protein. SRT is also effective against infection with SARS-CoV-2 PsV variants, including the newly emerging Omicron. The combination of SRT and other antivirals exhibits a strong synergistic effect against infection of SARS-CoV-2 PsV. The antiviral activity of SRT is independent of serotonin transporter expression. Moreover, SRT effectively inhibits infection of SARS-CoV-2 PsV and alleviates the inflammation process and lung pathological alterations in transduced mice in vivo. Therefore, SRT shows promise as a treatment option for COVID-19. IMPORTANCE The study shows SRT is an effective entry inhibitor against infection of SARS-CoV-2, which is currently prevalent globally. SRT targets the S protein of SARS-CoV-2 and is effective against a panel of SARS-CoV-2 variants. It also could be used in combination to prevent SARS-CoV-2 infection. More importantly, with long history of clinical use and proven safety, SRT might be particularly suitable to treat infection of SARS-CoV-2 in the central nervous system and optimized for treatment in older people, pregnant women, and COVID-19 patients with heart complications, which are associated with severity and mortality of COVID-19.

7.
Chinese Journal of School Health ; 43(10):1570-1573 and 1578, 2022.
Article in Chinese | Scopus | ID: covidwho-2145644

ABSTRACT

Objective To analyse monitoring absenteeism due to respiratory symptoms/diseases among preschoolers in Guang-zhou, and to provide reference for risk prevention and control of respiratory infectious diseases in kindergartens. Methods Data of absenteeism due to symptoms and diseases in kindergartens were collected from "Guangzhou Student Health Monitoring System", and was analyzed by using R 4.1.3 software. Results During 2018-2020 academic year, there were 1 965, 2 019, 2 236 kinder-gartens being monitored respectively. The absenteeism rate of kindergarten's children due to respiratory symptoms and diseases in Guangzhou were 3.08 ‰ and 2.02 ‰. The absenteeism rates due to respiratory symptoms were 3.75 ‰, 4.17 ‰, 2.97 ‰ and 2.09 ‰ in baby class, junior class, middle class and senior class, respectively. The absenteeism rates due to respiratory diseases were 2.34 ‰, 2.60 ‰, 1.94 ‰ and 1.50 ‰, respectively. The absenteeism rate in higher grade was lower than that in lower grade (X2 = 65 197.95, 27 929.44, P<0.01). The absenteeism rates of boys (3.11 ‰, 2.05 ‰ ) due to respiratory symptoms/diseases were signif-icantly higher than those of girls (3.06 ‰, 1.97 ‰ ) (X2 =57.71, 229.45, P<0.01). The absenteeism of preschoolers due to respiratory symptoms/diseases showed two peaks in December of the this year and May of the following year. At the beginning of the second se-mester of 2019 academic year (after the outbreak of Coronavirus disease 2019), the absenteeism rate due to respiratory symptoms/diseases were lower than those of the same period in previous years. Conclusions The absences due to respiratory symptoms or dis-eases not only accounted for half of the total absences due to illness, but also had seasonal characteristics. Children in the younger-age group and most boys are treated as a focus group for absence due to respiratory symptoms/illnesses. It's necessary to give full use of timely warning function of health monitoring system. © 2022 by the Author(s).

8.
Chinese Journal of Laboratory Medicine ; 45(9):987-991, 2022.
Article in Chinese | Scopus | ID: covidwho-2143859

ABSTRACT

The pandemic of 2019 novel coronavirus (2019-nCoV) infection since 2020 caused Coronavirus Disease 2019 (COVID-19) leads the serious threaten to global public health. It is urgent to diagnose COVID-19, guide epidemiological measures, control the infection rates, research/develop the antiviral treatment and promote the vaccine research. The application of nano-material based biosensors (the nano-biosensors) has achieved the high-performance detection of a variety of biomarkers due to their small device size, label free detection, high sensitivity, good specificity, short detection time, and has been considered as great potential to become a point-of-care testing tool for detecting 2019-nCoV. Therefore, by summarizing the working principle and classification of nano-biosensors, and focusing on the research progress of nano-biosensors in the detection of 2019-nCoV reported in the recent years, our review provides the challenges and future development prospects of the nano-biosensor in clinical laboratory. © 2022 Chin J Lab Med. All rights reserved.

9.
IEEE Power and Energy Magazine ; 20(6):47-55, 2022.
Article in English | Scopus | ID: covidwho-2107845

ABSTRACT

Over the past several years the electric power sector has been challenged by a number of extreme events around the globe. Significant societal and economic shocks were due to the rapid spread of COVID-19 around the world. In addition to the pandemic, there have been several extreme weather and societal disruptions to the electricity sector, such as the February 2021 Texas power outage and the 9 p.m. nine-minute blackout event in India. © 2003-2012 IEEE.

10.
IEEE Transactions on Engineering Management ; : 1-16, 2022.
Article in English | Scopus | ID: covidwho-2097663

ABSTRACT

COVID-19 is an epidemic threat to human health caused by a novel coronavirus. Different countries are still struggling with whether to extend lockdown policies considering economic recession outcomes or lift the lockdown and recover the fragile economy. This research narrows the knowledge gap by applying a decision-making approach in a fuzzy environment to consider the uncertainties in the supply chain risk assessment of the construction industry during the COVID-19 pandemic. Besides, risk factors (RFs) are identified and interrelationships between RFs are depicted. RFs are categorized using expert panel surveys and literature reviews. The interdependencies between different RFs are evaluated using a combination of interval-valued intuitionistic fuzzy numbers, decision making trial and evaluation laboratory, and the Choquet integral to allow a strong interrelationship between the sum of rows and the sum of columns of RFs in structural correlation analysis. Next, priorities of RFs are obtained by considering interdependencies between different RFs using a combination of the technique for order preference by similarity to the ideal solution (TOPSIS) method with the intuitionistic fuzzy set. An intuitionistic fuzzy weighted average operator is utilized to aggregate individual opinions of decision makers for rating the importance of RFs. Results reported that the scarcity of material and financial resources due to movement restrictions with overall weights of 0.0614 and 0.413 are the most prominent RFs in the supply chain due to the COVID-19 pandemic. The results of this research can assist decision-makers in developing strategic policies to prevail over the risk challenges and subsequently aid experts in redesigning supply chains. IEEE

11.
World Journal of Traditional Chinese Medicine ; 8(4):491-496, 2022.
Article in English | EMBASE | ID: covidwho-2066907

ABSTRACT

Photobiomodulation (PBM) therapy is a therapeutic method that can produce a range of physiological effects in cells and tissues using certain wavelengths. The reparative benefits of PBM therapy include wound healing, bone regeneration, pain reduction, and the mitigation of inflammation. Advances in the development of laser instruments, including the use of high-intensity lasers in physiotherapy, have recently led to controllable photothermal and photomechanical treatments that enable therapeutic effects to be obtained without damaging tissue. The combination of PBM therapy with acupuncture may provide new perspectives for investigating the underlying therapeutic mechanisms of acupuncture and promote its widespread application.

12.
10th IEEE International Conference on Healthcare Informatics, ICHI 2022 ; : 664-668, 2022.
Article in English | Scopus | ID: covidwho-2063259

ABSTRACT

Previous studies have documented an association of D-dimer levels with COVID-19 severity. Elevated D-dimer is reported to be associated with patient demographics, comorbidities, lab results, and overall higher incidence of critical illness. However, due to small sample sizes, limited availability of data on essential covariates, and lack of standardization of the admission laboratory protocol, the role of D-dimer in the progression of COVID-19 remains uncertain and needs further investigation using data from larger cohorts. The objectives of this study were to study the factors predicting elevated D-dimer level and to characterize the risk factors that predict D-dimer elevation over the course of inpatient admission. We used statistical modeling, applying machine learning methods to maximally leverage all the available clinical and care variables without being limited by the assumptions of traditional regression analysis methods. Our sample consisted of 1005 COVID-19 inpatients admitted to a large US hospital from March 2020 to July 2020, using detailed data on various clinical and biochemical laboratory test results at admission and throughout the course of hospital stay. Analytic methods used in this study included a) descriptive statistics at baseline using chi-square tests to compare patients with normal and elevated D-dimer at baseline, b) adjusted multivariable regression modeling, and c) evaluation of importance of each feature using two decision-tree-based supervised machine learning algorithms, random forest and XGBoost methods. Results show that machine learning methods could identify 20 important features that predict D-dimer some of which could be used to prevent the processes that lead to D-dimer elevation. Our study suggests that continual laboratory monitoring of D-dimer levels from the time of detection of COVID-19 infection, and monitoring of selected risk factors out of the panel of identified risk factors may enable clinicians to triage patients into risk levels, initiate appropriate therapeutic strategies, and tailor care management to each patient in order to minimize the morbidity and mortality of COVID-19. © 2022 IEEE.

13.
10th IEEE International Conference on Healthcare Informatics, ICHI 2022 ; : 481-482, 2022.
Article in English | Scopus | ID: covidwho-2063254

ABSTRACT

Although previous studies using limited data have documented an association of D-dimer levels with COVID-19 severity, the role of D-dimer in the progression of COVID-19 remains unclear and requires further investigation using data from larger cohorts. We used traditional statistical modeling and machine learning methods to examine critical factors influencing the D-dimer elevation and to characterize associated risk factors of D-dimer elevation over the course of inpatient admission. We identified 20 important features to predict D-dimer levels, some of which could be used to predict and prevent the D-dimer elevation. Laboratory monitoring of D-dimer level and its risk factors at early stage can mitigate severe or death cases in COVID-19. © 2022 IEEE.

14.
American Journal of Translational Research ; 14(9):6375-6381, 2022.
Article in English | EMBASE | ID: covidwho-2058689

ABSTRACT

From the start of the coronavirus disease 2019 (COVID-19) pandemic in 2020, COVID-19 infection in the pediatric population has aroused great attention. This article presents dynamic epidemiological characteristics of COVID-19 infection in pediatric patients from January 2020 to March 2022 in China. These data contributed essential insights and shared experience on the management of COVID-19 in children. To date, the unvaccinated population and events with children need more attention. Copyright © 2022 E-Century Publishing Corporation. All rights reserved.

15.
Journal of the Intensive Care Society ; 23(1):113-114, 2022.
Article in English | EMBASE | ID: covidwho-2043067

ABSTRACT

Background: Intra-oral kinking of endotracheal tube is a rare but not unheard of complication. It could be lifethreatening if left unrecognised. Case presentation: A ten-year-old boy with developmental delay, scoliosis and recurrent chest infections was transferred to our paediatric intensive care (PIC) with SARS-CoV-2 pneumonia. The child was intubated with a size 5.5 micro-cuff endotracheal tube for critical hypoxic respiratory failure at his local hospital. The intubation was reported to be straightforward, with a grade 1 laryngoscopy view, but he was notably difficult to ventilate and oxygenate on the ventilator. He was transferred by road and was requiring a fraction of inspired oxygen of 0.8 and inhaled nitric oxide at 20 parts per million to maintain oxygen saturations of greater than 94%. The retrieval team also reported that he required a peak inspiratory pressure of as high as 49 cmH2O and positive end-expiratory pressure of 8 cmH2O with a 1:1 I: E ratio to maintain tidal volume of 6 ml/kg for his weight of 30kg. He was fully sedated and paralysed. The child was examined on arrival to PIC. His trachea was central and there was no wheeze or abdominal distension. The capnography waveforms were of normal appearance. A chest X-ray was also done to exclude endobronchial intubation and obvious pneumothorax. He was noted to be unusually difficult to bag ventilate, and the delivery of tidal volumes were hugely variable with any change in head positioning. He was best ventilated with head-tilt and chin-lift. Our concerns were escalated when the 'red-flag' of inability to pass the suction catheter was highlighted by the nursing team. The course of his tracheal tube was immediately palpated, and a twist was felt in the oropharynx. This finding was confirmed on laryngoscopy, which revealed a significant kink at letter C of this micro-cuff tube (Figure 1). The airway was swiftly exchanged, and immediate improvements of both ventilation and gas exchanged were observed. Conclusion: The polyvinyl polymers of endotracheal tubes are known to soften at body temperature and have a higher tendency to bent at acute angles,1 where the pilot tubing exists2;and when bending forces are applied away from the anatomical curvature, also known as the Magill curve (radius of approximately 140 millimetres), of most conventional tracheal tubes.2-5 Kinking of endotracheal tube at blind spots such as within the pharynx may happen more frequently in paediatrics than in adult critical care practice due to the use of straighter tracheal tubes with smaller wall thickness. We would like to raise awareness of this unusual case of difficult bag ventilation and high airway pressure ventilation. If a well-secured tracheal tube suddenly becomes problematic following, or in relation to positional changes, tube malfunction should be suspected. The integrity of the endotracheal tube must also be interrogated.

16.
Journal of the Intensive Care Society ; 23(1):55-56, 2022.
Article in English | EMBASE | ID: covidwho-2043016

ABSTRACT

Introduction: Comparatively little is known about drug requirements in patients admitted to ICU with COVID-19 pneumonitis. We analysed drug usage for patients admitted during the first wave of the pandemic, comparing these with a retrospective cohort admitted with Influenza pneumonia. Methods: Forty-nine ventilated patients with COVID-19 pneumonitis were identified through ICNARC, ten were excluded as duration of stay < 7 days or not needing ventilation. Further three were excluded due to missing data and one due to ECMO escalation. Results: The median age was 61 years;length of stay 22 days and 68% survived ICU. Table 1 describes the use of Infusions and enteral medications. Discussion: Propofol was used in most (43% patient-hours in ICU/median duration = 234 hours). All patients received opiate infusions (mainly morphine or alfentanil in similar proportions) and 91% received muscle relaxants, for prolonged periods. Over half received Midazolam (median 106 hours) as an adjunct or substitute to Propofol as patients were difficult to sedate, required longer ventilation, paralysis and concerns with Propofol associated hypertriglyceridemia. Over two-third received alpha agonist infusions (median 68.5 hours) as adjunctive sedation or delirium management. Three quarters of patients received a furosemide infusion (median 90 hours), the evidence extrapolated from studies such as FACTT.1 Around three quarters received Human Albumin (median 100 grams over 3 days). Nearly a quarter received nebulized Prostacyclin for refractory hypoxia, often associated with saturation of HME filters and ventilatory difficulties.2 Over half of patients received Carbocisteine (median 13 days). Clonidine and Risperidone to manage delirium were used in a third (median 10.5 and 11 days respectively), as was Acetazolamide to restore pH and aid weaning. Over a third were prescribed enteral opiates and nearly a quarter received benzodiazepines to manage withdrawal symptoms. Just under a half of patients received Melatonin. Antibiotic usage was high with a median of 3 Antibiotics used (median duration 15 days/61% of patient days). Diagnosing superadded infection such as VAP was challenging3 and we did not routinely monitor serum Procalcitonin levels. We also compared prescribing habits with 12 influenza patients (11 survivors) identified using similar inclusion criteria and found patients with COVID-19 were older (61 versus 51 years ) with longer ICU stays (median 22 versus 20 days). They were also more likely to receive enteral Carbocisteine, Clonidine, Acetazolamide, Morphine and Diazepam. Conclusion: We were able to generate valuable data on prescribing in ventilated patients with COVID-19 pneumonitis during the first wave. Through this, we are able to use drug usage as a surrogate for issues such as delirium, drug withdrawal, antibiotic prescribing and nursing workload in general.

17.
Digital Innovation for Healthcare in COVID-19 Pandemic: Strategies and Solutions ; : 189-199, 2022.
Article in English | Scopus | ID: covidwho-2027780

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a global pandemic that significantly challenged healthcare systems worldwide, with over 4 million deaths among 18.6 million identified cases as of June 2021. Understanding the current COVID-19 cases and determining clinical solutions is of paramount importance. In this chapter, we describe an exploratory study of identifying risk factors associated with COVID-19 inpatient care. Based on a set of COVID-19 inpatient medical health records in a US hospital system, we used both unsupervised and supervised machine learning methods to explore risk factors associated with hospitalized COVID-19 patients. We found that the most important features related to the COVID-19 disease include (1) influenza vaccines, (2) pneumococcal vaccines, and (3) weight-related variables (i.e., weight, height, and BMI). As such, we provide a use case that machine learning methods are valuable for predicting COVID-19 inpatient risk factors, and the results are promising to guide further research in this area. © 2022 Elsevier Inc. All rights reserved.

18.
American Journal of Translational Research ; 14(6):3603-3609, 2022.
Article in English | EMBASE | ID: covidwho-2006937

ABSTRACT

SARS-CoV-2 variants have shown increased transmission capabilities and pandemic to an extent with severe presentation and mortality. The delta variant has been declared as an emerging variant of concern (VOC) by the World Health Organization (WHO) on May 10, 2021. This review summarizes the post-vaccination infection events related to SARS-CoV-2 delta variant outbreaks in many areas of China. The characteristics and measures of delta variant-induced COVID-19 infections from May 2021 to October 2021 were reported. We compared the delta variant with the omicron from the latest literature review.

19.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927905

ABSTRACT

Disorders in pulmonary vascular integrity are a prominent feature in many lung diseases, including acute respiratory distress syndrome (ARDS), capillary leak syndrome, and COVID19. Paracrine signals are enriched in the lung and are critically important in regulating the homeostasis of the functional pulmonary microvasculature. Here, we employed single-cell RNA-sequencing (scRNAseq) to study ligand and receptor interactions in the native human lung microvascular niche, and identified soluble factors that are critical in endothelial integrity. The scRNAseq data reveals a total of 47 cell populations consisting of five vascular endothelial subtypes in human lungs, including general capillary EC, aerocyte capillary EC (EC aCap), arterial EC, pulmonary venous EC, and systemic venous EC. Using EC aCap as a signal receiving core (Receptors) and the putative adjacent cell types (alveolar fibroblast, ATI, ATII, pericyte, plasma cell, etc.) in the EC aCap niche as senders (Ligands), we identified that SLIT2-ROBO4, ANGPT1-TIE1, ADM-RAMP2, VEGFD-KDR, and BMP5-BMPR2 are the top specific and abundant pairs in the niche. Immunostaining and ELISA assays confirmed their spatial information and secretion level. Furthermore, upon treatment with these ligands, real-time resistance recorded using an electric cell-substrate impedance sensing (ECIS) system revealed that VEGFD, ANGPT1 (angiopoietin 1), and ADM (adrenomedullin) could markedly increase the electrical resistance of human lung microvascular, arterial, and venous endothelial cells, suggesting their strong impact on the endothelial barrier function. Deciphering the cell-cell soluble signals that improve endothelial integrity in human lungs lays the foundation for uncovering the pathogenesis of pulmonary vascular disorders and the development of ex vivo functional lung vasculature.

20.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925543

ABSTRACT

Objective: To expand understanding of the human immunological response to SARS-CoV-2 vaccination in patients with Multiple Sclerosis (MS) treated with anti-CD20 monoclonal therapy and sphingosine-1-phosphate (S1P) modulators. Background: Immunomodulatory therapy prescribed for patients with MS has been associated with decreased or absent anti-SARS-CoV-2 immunoglobulin production following COVID-19 vaccination. We investigate broader adaptive immune responses to SARS-CoV-2 vaccination measuring IgG immunoglobulin production and T-cell reactivity in a small cohort. Design/Methods: We used the Stanford Research Repository database to identify 55 MS patients by ICD10 code who were tested for B-cell and T-cell responses via SARS-CoV-2-IgG and SARS-CoV-2 Interferon Gamma Release Assay (IGRA), respectively. 96% (53/55) of patients were fully vaccinated (98% mRNA/2% Janssen). A Chi-square test compared differences in vaccine response between 3 different disease modifying treatment (DMT) groups: anti-CD20 therapy (n=24), S1P modulators (n=11), and off DMT/other MS therapies (n=20). Results: In patients on anti-CD20 therapy, 71% (17/24) were positive for SARS-CoV-2 IGRA but negative for SARS-CoV-2 IgG, among which 65% (11/17) had low CD-19 levels (0-64 cells/uL, normal 100-500 cells/uL) with normal absolute lymphocyte count (ALC). Among patients who delayed vaccination by 4-6 months following anti-CD20 therapy, 13% (3/24) expressed SARS-CoV-2-IgG. 82% (9/11) of patients on S1P modulators showed absent SARS-CoV-2-IgG and SARS-CoV-2 IGRA responses, in association with low ALC (range 210-600 cells/uL, normal 1000-3000 cells/uL). 95% (19/20) of patients off DMT/on other MS therapies showed positive SARS-CoV-2-IgG and SARS-CoV-2 IRGA responses. All vaccinated patients were assessed between 4 weeks and 6 months post-vaccination. These differential responses between treatment groups were significant (p<0.05). Conclusions: We demonstrate that among MS patients treated with anti-CD20 therapy, T-cell response was largely preserved despite greatly reduced B-cell response to SARS-CoV-2 vaccination. MS patients on S1P modulators demonstrated absence of both B-cell and T-cell response. The clinical correlation of this is to be determined.

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