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1.
Front Psychol ; 12: 601383, 2021.
Article in English | MEDLINE | ID: covidwho-1608970

ABSTRACT

In the environment of COVID-19, people are faced with mortality salience (MS) and socioeconomic crisis. According to the terror management theory, the MS would lead to particular consumption attitudes and behaviors caused by the self-esteem and cultural worldview defense. The creativity as a potential value of products needs to be examined to explore how the MS changed the creativity evaluation of three types of products categorized into normal, renovative, and innovative products, based on the degree of originality (Zhang et al., 2019). Two experiments were conducted to examine (1) the MS effect on the creativity and purchase intention evaluation and (2) both MS and country-of-origin effect on the evaluations. The results show that usefulness and purchase intention are affected by both effects, and the novelty is mainly affected by MS.

2.
Neural Regen Res ; 17(7): 1576-1581, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1575953

ABSTRACT

Although some short-term follow-up studies have found that individuals recovering from coronavirus disease 2019 (COVID-19) exhibit anxiety, depression, and altered brain microstructure, their long-term physical problems, neuropsychiatric sequelae, and changes in brain function remain unknown. This observational cohort study collected 1-year follow-up data from 22 patients who had been hospitalized with COVID-19 (8 males and 11 females, aged 54.2 ± 8.7 years). Fatigue and myalgia were persistent symptoms at the 1-year follow-up. The resting state functional magnetic resonance imaging revealed that compared with 29 healthy controls (7 males and 18 females, aged 50.5 ± 11.6 years), COVID-19 survivors had greatly increased amplitude of low-frequency fluctuation (ALFF) values in the left precentral gyrus, middle frontal gyrus, inferior frontal gyrus of operculum, inferior frontal gyrus of triangle, insula, hippocampus, parahippocampal gyrus, fusiform gyrus, postcentral gyrus, inferior parietal angular gyrus, supramarginal gyrus, angular gyrus, thalamus, middle temporal gyrus, inferior temporal gyrus, caudate, and putamen. ALFF values in the left caudate of the COVID-19 survivors were positively correlated with their Athens Insomnia Scale scores, and those in the left precentral gyrus were positively correlated with neutrophil count during hospitalization. The long-term follow-up results suggest that the ALFF in brain regions related to mood and sleep regulation were altered in COVID-19 survivors. This can help us understand the neurobiological mechanisms of COVID-19-related neuropsychiatric sequelae. This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University (approval No. 2020S004) on March 19, 2020.

3.
Preprint in English | Other preprints | ID: ppcovidwho-296158

ABSTRACT

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host ACE2 receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (–)-hopeaphenol, a resveratrol tetramer, in addition to vatalbinoside A and vaticanol B, as potent and selective inhibitors of RBD/ACE2 binding and viral entry. For example, (–)-hopeaphenol disrupted RBD/ACE2 binding with a 50% inhibitory concentration (IC50) of 0.11 μM in contrast to an IC50 of 28.3 μM against the unrelated host ligand/receptor binding pair PD-1/PD-L1 (selectivity index = 257.3). When assessed against the USA-WA1/2020 variant, (–)-hopeaphenol also inhibited entry of a VSVΔG-GFP reporter pseudovirus expressing SARS-CoV-2 spike into ACE2-expressing Vero-E6 cells and in vitro replication of infectious virus in cytopathic effect assays (IC50 = 10.2 μM) without cytotoxicity. Notably, (–)- hopeaphenol also inhibited two emerging variants of concern originating from the United Kingdom (B.1.1.7) and South Africa (B.1.351) in both cytopathic effect and spike-containing pseudovirus assays with similar (B.1.1.7) or improved (B.1.351) efficacies over the USA- WA1/2020 variant. These results identify (–)-hopeaphenol and related stilbenoid analogues as potent and selective inhibitors of viral entry across multiple SARS-CoV-2 variants including those with increased infectivity and/or reduced susceptibility to existing vaccines. Importance SARS-CoV-2 antivirals are needed to supplement existing vaccine efforts and target emerging viral variants with increased infectivity or reduced susceptibility to existing vaccines. Here we show that (–)-hopeaphenol, a naturally-occurring stilbenoid compound, in addition to its analogues vatalbinoside A and vaticanol B, inhibit SARS-CoV-2 by blocking the interaction of the viral spike protein with the cellular ACE2 entry receptor. Importantly, in addition to inhibiting the early USA-WA1/2020 SARS-CoV-2 variant, hopeaphenol also inhibits emerging variants of concern including B.1.1.7 (“United Kingdom variant”) and B.1.351 (“South Africa variant”), with improved efficacy against B.1.351. (–)-Hopeaphenol therefore represents a new antiviral lead against infection from multiple SARS-CoV-2 variants.

4.
Preprint in English | EuropePMC | ID: ppcovidwho-295831

ABSTRACT

Synthetic glucocorticoids are used to treat many immune conditions, such as asthma and severe COVID-19. Single cell data capture fine-grained details of transcriptional variability and dynamics to gain a better understanding of the molecular underpinnings of inter-individual variation in drug response. We used single cell RNA-seq to study the dynamics of the transcriptional response to glucocorticoids in activated PBMCs from African American donors. We employed novel statistical approaches to calculate a mean-independent measure of gene expression variability and a measure of transcriptional response pseudotime. We demonstrated that glucocorticoids reverse the effects of immune stimulation on both gene expression mean and variability. Our novel measure of gene expression response dynamics separated cells by response status and identified dynamic transcriptional patterns along the response pseudotime. We identified genetic variants regulating gene expression mean and variability, including treatment-specific effects, and demonstrated widespread genetic regulation of the transcriptional dynamics of the gene expression response. Synthetic glucocorticoids, such as dexamethasone, have been used as treatment for many immune conditions, such as asthma and more recently severe COVID-19. Single cell data can capture more fine-grained details on transcriptional variability and dynamics to gain a better understanding of the molecular underpinnings of inter-individual variation in drug response. Here, we used single cell RNA-seq to study the dynamics of the transcriptional response to glucocorticoids in activated PBMCs from 96 African American donors. We employed novel statistical approaches to calculate a mean-independent measure of gene expression variability and a measure of transcriptional response pseudotime. Using these approaches, we demonstrated that glucocorticoids reverse the effects of immune stimulation on both gene expression mean and variability. Our novel measure of gene expression response dynamics, based on the diagonal linear discriminant analysis, separated cells by response status on the basis of their transcriptional profiles and allowed us to identify different dynamic patterns of gene expression along the response pseudotime. We identified genetic variants regulating gene expression mean and variability, including treatment-specific effects, and demonstrated widespread genetic regulation of the transcriptional dynamics of the gene expression response.

5.
Antimicrob Agents Chemother ; 65(12): e0077221, 2021 11 17.
Article in English | MEDLINE | ID: covidwho-1522896

ABSTRACT

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host angiotensin-converting enzyme II (ACE2) receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here, we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (-)-hopeaphenol, a resveratrol tetramer, in addition to vatalbinoside A and vaticanol B, as potent and selective inhibitors of RBD/ACE2 binding and viral entry. For example, (-)-hopeaphenol disrupted RBD/ACE2 binding with a 50% inhibitory concentration (IC50) of 0.11 µM, in contrast to an IC50 of 28.3 µM against the unrelated host ligand/receptor binding pair PD-1/PD-L1 (selectivity index, 257.3). When assessed against the USA-WA1/2020 variant, (-)-hopeaphenol also inhibited entry of a VSVΔG-GFP reporter pseudovirus expressing SARS-CoV-2 spike into ACE2-expressing Vero-E6 cells and in vitro replication of infectious virus in cytopathic effect and yield reduction assays (50% effective concentrations [EC50s], 10.2 to 23.4 µM) without cytotoxicity and approaching the activities of the control antiviral remdesivir (EC50s, 1.0 to 7.3 µM). Notably, (-)-hopeaphenol also inhibited two emerging variants of concern, B.1.1.7/Alpha and B.1.351/Beta in both viral and spike-containing pseudovirus assays with similar or improved activities over the USA-WA1/2020 variant. These results identify (-)-hopeaphenol and related stilbenoid analogues as potent and selective inhibitors of viral entry across multiple SARS-CoV-2 variants of concern.


Subject(s)
COVID-19 , Stilbenes , Humans , Pandemics , Phenols , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
6.
Front Psychol ; 12: 617967, 2021.
Article in English | MEDLINE | ID: covidwho-1518528

ABSTRACT

For much of 2020, countries around the world fought against the COVID-19 pandemic. Many countries went into lockdown to control the fast spread of the virus. The unusual restrictions and confinement of the lockdown brought about new challenges for people's everyday lives. With flexibility, adaptability, and problem-solving at the core of its nature, creativity has the potential to help people cope with harsh and uncertain circumstances. Were people more, the same, or less creative in their everyday life during the period of lockdown, and in which ways? What are the emotions and motivations underlying their creative or non-creative behaviors? The current study aims to explore these questions from a cross-cultural perspective. A total of 754 comparable employee samples from three Chinese and three German cities were asked about their moods during the lockdown period, their self-rated level of creativity in daily lives before and during the lockdown, and their motivations behind their creative activities. Significant increases in creativity were observed in all everyday activities in both countries with only two exceptions in the German sample. Despite minor differences, a common pattern was found across cultures: whereas the activating positive mood could directly lead to the increase in creativity in some everyday activities, such a direct Mood-Creativity link was limited in the activating negative mood circumstances. In such circumstances, motivation intervened to enable the link to creativity. It was also found that this indirect effect of motivation between mood and creativity was more pronounced with the German participants.

9.
Front Med (Lausanne) ; 8: 659793, 2021.
Article in English | MEDLINE | ID: covidwho-1497084

ABSTRACT

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

10.
Stat Med ; 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1482171

ABSTRACT

Timely diagnostic testing for active SARS-CoV-2 viral infections is key to controlling the spread of the virus and preventing severe disease. A central public health challenge is defining test allocation strategies with limited resources. In this paper, we provide a mathematical framework for defining an optimal strategy for allocating viral diagnostic tests. The framework accounts for imperfect test results, selective testing in certain high-risk patient populations, practical constraints in terms of budget and/or total number of available tests, and the purpose of testing. Our method is not only useful for detecting infections, but can also be used for long-time surveillance to detect new outbreaks. In our proposed approach, tests can be allocated across population strata defined by symptom severity and other patient characteristics, allowing the test allocation plan to prioritize higher risk patient populations. We illustrate our framework using historical data from the initial wave of the COVID-19 outbreak in New York City. We extend our proposed method to address the challenge of allocating two different types of diagnostic tests with different costs and accuracy, for example, the RT-PCR and the rapid antigen test (RAT), under budget constraints. We show how this latter framework can be useful to reopening of college campuses where university administrators are challenged with finite resources for community surveillance. We provide a R Shiny web application allowing users to explore test allocation strategies across a variety of pandemic scenarios. This work can serve as a useful tool for guiding public health decision-making at a community level and adapting testing plans to different stages of an epidemic. The conceptual framework has broader relevance beyond the current COVID-19 pandemic.

12.
Front Artif Intell ; 4: 672050, 2021.
Article in English | MEDLINE | ID: covidwho-1430749

ABSTRACT

Cohort-independent robust mortality prediction model in patients with COVID-19 infection is not yet established. To build up a reliable, interpretable mortality prediction model with strong foresight, we have performed an international, bi-institutional study from China (Wuhan cohort, collected from January to March) and Germany (Würzburg cohort, collected from March to September). A Random Forest-based machine learning approach was applied to 1,352 patients from the Wuhan cohort, generating a mortality prediction model based on their clinical features. The results showed that five clinical features at admission, including lymphocyte (%), neutrophil count, C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase, could be used for mortality prediction of COVID-19 patients with more than 91% accuracy and 99% AUC. Additionally, the time-series analysis revealed that the predictive model based on these clinical features is very robust over time when patients are in the hospital, indicating the strong association of these five clinical features with the progression of treatment as well. Moreover, for different preexisting diseases, this model also demonstrated high predictive power. Finally, the mortality prediction model has been applied to the independent Würzburg cohort, resulting in high prediction accuracy (with above 90% accuracy and 85% AUC) as well, indicating the robustness of the model in different cohorts. In summary, this study has established the mortality prediction model that allowed early classification of COVID-19 patients, not only at admission but also along the treatment timeline, not only cohort-independent but also highly interpretable. This model represents a valuable tool for triaging and optimizing the resources in COVID-19 patients.

13.
Front Med (Lausanne) ; 8: 678157, 2021.
Article in English | MEDLINE | ID: covidwho-1417107

ABSTRACT

Purpose: This study aimed to describe the clinical and laboratory characteristics and the parameters of the respiratory mechanics of mechanically ventilated patients with confirmed COVID-19 pneumonia and to clarify the risk or protective factors for weaning failure. Methods: Patients diagnosed with COVID-19 pneumonia were selected from the special intensive care unit (ICU) of the Sino-French New City Branch of Tong Ji Hospital, Wuhan, and treated by the National Medical Team Work. They were divided into successful weaning (SW) group (N = 15) and unsuccessful weaning (USW) group (N = 18) according to the prognosis. Information of these patients was analyzed. Results: There were 33 patients included in this study. Patients in the USW group were associated with a poor outcome; the 28-day mortality rate was higher than in the SW group (86.7 vs. 16.7% p < 0.001). By comparison, we found that the initial plateau pressure (Pplat) and driving pressure (DP) of the USW group were higher and that compliance was lower than that of the SW group, but there was no difference between positive end-expiratory pressure (PEEP), partial pressure of carbon dioxide (PCO2), and the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (P/F ratio). Comparing the worst respiratory mechanics parameters of the two groups, the results of the Pplat, DP, compliance, and PEEP were the same as the initial data. The PCO2 of the USW group was higher, while the P/F ratio was lower. A logistic regression analysis suggested that higher Pplat might be an independent risk factor and that higher compliance and lower DP might be protective factors for weaning failure of invasive mechanically ventilated patients with COVID-19 pneumonia. Conclusions: Patients with USW were associated with a poor outcome, higher Pplat might be a risk factor, and a higher compliance and a lower DP might be protective factors for the weaning failure of ventilated COVID-19 patients. Mechanical ventilation settings will affect the patient's prognosis.

14.
Annals of Hematology ; 100(3):843-846, 2021.
Article in English | CAB Abstracts | ID: covidwho-1408352

ABSTRACT

In total, we identified five Caucasian patients from Wurzburg (Nos. 1-5) and three Asian patients from Wuhan (Nos. 6-8). The majority of the patients were male (n = 5, 63%), and the median age at COVID-19 diagnosis was 57 (range 39-83 years). The three patients from Wuhan were infected by COVID-19 in January or February 2020, while the Wurzburg patients were diagnosed in March or April 2020. Due to COVID-19 infection, anti-MM treatment was discontinued in all the patients. Notably, two patients (Nos. 3-4) in Wurzburg showed no COVID-19 symptoms, and the other three patients (Nos. 1, 2, and 5) exhibited only mild symptoms such as fever, cough, and nausea, which did not require an intensive care unit (ICU) admission. Interestingly, approximately 3 weeks after diagnosis, as the patient No. 6 was discharged and the swab was also negative for COVID-19, both COVID-19 IgM and IgG were tested negative in this patient. In four patients from Wurzburg, we also performed COVID-19 antibody test after recovery, and three of them (Nos. 1, 2, and 5) showed positive IgG, while one patient (No. 3) did not develop IgG or IgM against COVID-19. This finding suggested inadequate humoral immune response in MM patients, probably due to secondary immune deficiency caused by the treatments or the disease itself. This observation suggested that it might be a nosocomial infection in this patient. After recovery, two patients from Wurzburg received MM therapy, i.e., lenalidomide maintenance in one patient and DARA-VRCD (daratumumab, bortezomib, lenalidomide, cyclophosphamide, and dexamethasone) in another patient with NDMM.

15.
Couple and Family Psychology: Research and Practice ; : No Pagination Specified, 2021.
Article in English | APA PsycInfo | ID: covidwho-1373358

ABSTRACT

Many parents of children under age 18 are faced with additional COVID-19 parenting-related stressors and may be experiencing increases in psychological difficulties;however, we have yet to investigate parent's levels of posttraumatic stress symptoms (PTSS) and adjustment disorder. Further, COVID-19 has served as a sobering reminder of the significant public health disparities in our society and it is critical to identify risk factors for poorer clinical outcomes. The primary objectives of the present study were to: (a) determine whether parents are reporting higher levels of pandemic-related stress, PTSS, and adjustment disorder than controls, (b) identify specific individual-level factors (e.g., age, gender, race, number of children, age of children) that may be related to higher levels of stress and symptoms among parents, and (c) report parents' utilization of, and perceived efficacy of, psychological interventions during COVID-19. A U.S. nationally representative sample (N = 2,019) from Qualtrics Data panels was recruited in July-August 2020. Parents endorsed higher levels of stress, PTSS, and adjustment disorder, particularly younger parents. Further, 38.3% of parents reported PTSS above clinical cutoff. Younger participants and persons of color reported higher levels of pandemic-related stress. One-third of parents (33.1%) reported using online mental health services. Taken together, parents may be at greater risk for pandemic stress, PTSS, and adjustment disorder symptoms. Individual-level risk factors, such as age and minority status, are important to consider when understanding COVID-19 stress. Clinical intervention efforts should prioritize trauma-focused treatments for parents, especially those who are younger and identify as a person of color. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

16.
Signal Transduct Target Ther ; 6(1): 304, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1361622

ABSTRACT

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host's innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Humoral , SARS-CoV-2/immunology , Viral Nonstructural Proteins/immunology , COVID-19/mortality , Critical Illness , Disease-Free Survival , Epitopes/immunology , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Protein Array Analysis , Survival Rate
17.
Front Med (Lausanne) ; 8: 654658, 2021.
Article in English | MEDLINE | ID: covidwho-1325536

ABSTRACT

Purpose: A phenotype of COVID-19 ARDS patients with extremely low compliance and refractory hypercapnia was found in our ICU. In the context of limited number of ECMO machines, feasibility of a low-flow extracorporeal carbon dioxide removal (ECCO2R) based on the renal replacement therapy (RRT) platform in these patients was assessed. Methods: Single-center, prospective study. Refractory hypercapnia patients with COVID-19-associated ARDS were included and divided into the adjusted group and unadjusted group according to the level of PaCO2 after the application of the ECCO2R system. Ventilation parameters [tidal volume (VT), respiratory rate, and PEEP], platform pressure (Pplat) and driving pressure (DP), respiratory system compliance, arterial blood gases, and ECCO2R system characteristics were collected. Results: Twelve patients with refractory hypercapnia were enrolled, and the PaCO2 was 64.5 [56-88.75] mmHg. In the adjusted group, VT was significantly reduced from 5.90 ± 0.16 to 5.08 ± 0.43 ml/kg PBW; DP and Pplat were also significantly reduced from 23.5 ± 2.72 mmHg and 29.88 ± 3.04 mmHg to 18.5 ± 2.62 mmHg and 24.75 ± 3.41 mmHg, respectively. In the unadjusted group, PaCO2 decreased from 94 [86.25, 100.3] mmHg to 80 [67.50, 85.25] mmHg but with no significant difference, and the DP and Pplat were not decreased after weighing the pros and cons. Conclusions: A low-flow ECCO2R system based on the RRT platform enabled CO2 removal and could also decrease the DP and Pplat significantly, which provided a new way to treat these COVID-19 ARDS patients with refractory hypercapnia and extremely low compliance. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT04340414.

18.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1324576

ABSTRACT

In single cell analyses, cell types are conventionally identified based on expressions of known marker genes, whose identifications are time-consuming and irreproducible. To solve this issue, many supervised approaches have been developed to identify cell types based on the rapid accumulation of public datasets. However, these approaches are sensitive to batch effects or biological variations since the data distributions are different in cross-platforms or species predictions. In this study, we developed scAdapt, a virtual adversarial domain adaptation network, to transfer cell labels between datasets with batch effects. scAdapt used both the labeled source and unlabeled target data to train an enhanced classifier and aligned the labeled source centroids and pseudo-labeled target centroids to generate a joint embedding. The scAdapt was demonstrated to outperform existing methods for classification in simulated, cross-platforms, cross-species, spatial transcriptomic and COVID-19 immune datasets. Further quantitative evaluations and visualizations for the aligned embeddings confirm the superiority in cell mixing and the ability to preserve discriminative cluster structure present in the original datasets.


Subject(s)
COVID-19/genetics , SARS-CoV-2/genetics , Single-Cell Analysis , Transcriptome/genetics , COVID-19/virology , Humans , RNA-Seq , SARS-CoV-2/isolation & purification , Species Specificity , Whole Exome Sequencing
19.
Cell Res ; 31(8): 836-846, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275907

ABSTRACT

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.


Subject(s)
COVID-19/pathology , Lung/virology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , Autopsy , COVID-19/virology , China , Cohort Studies , Critical Illness , Female , Fibrosis , Hospitalization , Humans , Kidney/pathology , Kidney/virology , Leukocytes, Mononuclear/pathology , Leukocytes, Mononuclear/virology , Lung/pathology , Male , Middle Aged , RNA, Viral/metabolism , SARS-CoV-2/genetics , Spleen/pathology , Spleen/virology , Trachea/pathology , Trachea/virology
20.
Ann Transl Med ; 9(10): 883, 2021 May.
Article in English | MEDLINE | ID: covidwho-1257380

ABSTRACT

Background: Cardiovascular involvement manifesting as arrhythmias has been confirmed in patients with coronavirus disease 2019 (COVID-19), so we aimed to explore the association between primary tachyarrhythmia and death in critically ill patients with COVID-19 in this retrospective study. Methods: A total of 79 critically ill patients with COVID-19 were included. Demographic characteristics, clinical data (past history, vital signs, therapeutic management, and outcomes), and results of laboratory findings and cardiac investigations were collected. All statistical analyses were performed using SPSS 23.0 software (IBM, Armonk, NY, USA). Results: The median age was 65±12 years, and 53 patients (67%) were male. A total of 57 (72%) patients died, and compared with survivors, these patients were older and had significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score and fewer lymphocytes as well as higher heart rate (P<0.05). Autopsy findings did not suggest severe myocarditis. A total of 19 (24%) patients had tachyarrhythmias, including 10 (13%) with atrial fibrillation (AF) and 9 (11%) with ventricular tachycardia or fibrillation. The incidence of tachyarrhythmias in non-survivor was much higher than in survivors (P=0.04). In a Cox regression model, older patients with ventricular tachyarrhythmias (VTAs) age were at a higher risk of death, with hazard ratio (HR) of 3.302 [95% confidence interval (CI), 1.524-7.154, P=0.002] and 1.045 (95% CI, 1.020-1.071, P=0.000), respectively. The use of beta-blockers [HR, 0.219 (95% CI, 0.066-0.722); P=0.013] was associated with a lower risk of death. Conclusions: Critically ill patients with COVID-19 had a poor prognosis. VTA and older age were independent prognostic factors of death. Beta-blockers might be an effective therapy to improve survival.

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