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1.
Thromb Res ; 2022 Nov 05.
Article in English | MEDLINE | ID: covidwho-2211518

ABSTRACT

BACKGROUND: The balance between thrombosis and hemostasis is a difficult issue during extracorporeal membrane oxygenation (ECMO) support. The pathogenesis leading to thrombotic complications during ECMO support is not well understood. Neutrophil extracellular traps (NETs) were reported to participate in thrombosis and have a key role in inflammation. This study aimed to explore the role of NETs in thrombosis during ECMO support and investigate NETs as a predictive biomarker for thrombotic complications during ECMO assistance. METHODS: Ten ovine models of ECMO support were established. Animals were then randomly divided into 2 groups (5 sheep/group): venoarterial (VA) ECMO group and venovenous (VV) ECMO group. The venous blood samples were collected at different time points. Markers of NETs were detected in plasma, neutrophils, and thrombi from the vessels and membrane. Moreover, circulating NETs levels in 8 adults treated in the intensive care unit (ICU) who received VA-ECMO and 8 healthy controls were detected; patient survival was also recorded. RESULTS: In vivo study showed that neutrophils and NETs markers (dsDNA and citH3) levels were significantly elevated 6 h after ECMO compared to baseline. Isolated neutrophils from fresh blood at 6 h could release more NETs. dsDNA and citH3 levels were significantly higher in the VA mode than in the VV mode. NETs were found in thrombi from the vessel and membrane. Clinical data further revealed that dsDNA, citH3, and nucleosomes were higher in patients who received ECMO than in healthy controls. CONCLUSIONS: These data suggest NETs might be associated with thrombus during ECMO support, especially in the VA mode. These findings provide new insight into preventing thrombotic complications by targeting NETs. Also, NETs may potentially become an early warning biomarker for thrombosis under ECMO assistance.

2.
Information Sciences ; 622:424-436, 2023.
Article in English | ScienceDirect | ID: covidwho-2149899

ABSTRACT

The clarity of medical images is crucial for doctors to identify and diagnose different diseases. High-resolution images have more detailed information and clearer content than low-resolution images. It is well known that medical images can frequently have some blurred object boundaries, and that traditional deep learning models cannot adequately describe the uncertainty of these blurred boundaries. This paper proposes a new fuzzy metric to characterize the uncertainty of pixels and designs a fuzzy hierarchical fusion attention neural network based on multiscale guided learning. Specifically, a fuzzy neural information-processing block is proposed, which converts an input image into a fuzzy domain using fuzzy membership functions. The uncertainty of the pixels is processed using the proposed fuzzy rules, and then the output of the fuzzy rule layer is fused with the result of the convolution in the neural network. Simultaneously, a multiscale guided-learning dense residual block and pyramidal hierarchical attention module are designed to extract more effective hierarchical image information. Finally, a recurrent memory module with a residual structure is used to process the output features of the hierarchical attention modules. A recursive sub-pixel reconstruction module is used at the tail of the network to reconstruct the images. Compared with existing super-resolution methods using the public COVID-CT dataset, the proposed method demonstrated superior performance in high-resolution medical image reconstruction and reduced the number of parameters and analysis time of the models.

3.
Biochemical Pharmacology ; : 115370, 2022.
Article in English | ScienceDirect | ID: covidwho-2149379

ABSTRACT

Cardiovascular disease is the major cause of mortality and disability, with hypertension being the most prevalent risk factor. Excessive activation of the renin-angiotensin system (RAS) under pathological conditions, leading to vascular remodeling and inflammation, is closely related to cardiovascular dysfunction. The counter-regulatory axis of the RAS consists of angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7), angiotensin (1-9), alamandine, proto-oncogene Mas receptor, angiotensin II type-2 receptor and Mas-related G protein-coupled receptor member D. Each of these components has been shown to counteract the effects of the overactivated RAS. In this review, we summarize the latest insights into the complexity and interplay of the counter-regulatory RAS axis in hypertension, highlight the pathophysiological functions of ACE2, a multifunctional molecule linking hypertension and COVID-19, and discuss the function and therapeutic potential of targeting this counter-regulatory RAS axis to prevent and treat hypertension in the context of the current COVID-19 pandemic.

4.
Perfusion ; : 2676591221130886, 2022 Oct 01.
Article in English | MEDLINE | ID: covidwho-2053623

ABSTRACT

PURPOSE: Extracorporeal membrane oxygenation (ECMO) is employed to support critically ill COVD-19 patients. The occurrence of ischemic stroke and intracranial hemorrhage (ICH), as well as the implementation of anticoagulation strategies under the dual influence of ECMO and COVID-19 remain unclear. We conducted a systematic review and meta-analysis to describe the ischemic stroke, ICH and overall in-hospital mortality in COVID-19 patients receiving ECMO and summarize the anticoagulation regimens. METHODS: EMBASE, PubMed, Cochrane, and Scopus were searched for studies examining ischemic stroke, ICH, and mortality in COVID-19 patients supported with ECMO. The outcomes were incidences of ischemic stroke, ICH, overall in-hospital mortality and anticoagulation regimens. We calculated the pooled proportions and 95% confidence intervals (CIs) to summarize the results. RESULTS: We analyzed 12 peer-reviewed studies involving 6039 COVID-19 patients. The incidence of ischemic stroke had a pooled estimate of 2.2% (95% CI: 1.2%-3.2%). The pooled prevalence of ICH was 8.0% (95% CI: 6.3%-9.6%). The pooled estimate of overall in-hospital mortality was 40.3% (95% CI: 33.1%-47.5%). The occurrence of ICH was significantly higher in COVID-19 patients supported with ECMO than in other respiratory ECMO [relative risk=1.75 (95% CI: 1.00-3.07)]. Unfractionated heparin was the most commonly used anticoagulant, and anticoagulation monitoring practice varied among centers. CONCLUSIONS: Ischemic stroke and ICH were common under the double "hit" of COVID-19 and ECMO. The prevalence of ICH was significantly higher in COVID-19 patients supported with ECMO than non-COVID-19 patients requiring ECMO. Individualized anticoagulation regimens may be a good choice to balance thrombosis and bleeding. More detailed research and further exploration are needed to clarify the underlying mechanism and clinical management decisions.

5.
Acta Academiae Medicinae Wannan ; 39(6):573-576, 2020.
Article in Chinese | GIM | ID: covidwho-2040044

ABSTRACT

Objective: To assess the clinical value of initial chest CT findings in patients with COVID-19.

6.
Front Psychiatry ; 13: 872331, 2022.
Article in English | MEDLINE | ID: covidwho-2032821

ABSTRACT

Background: The sporadic coronavirus disease (COVID-19) epidemic has placed enormous psychological stress on people, especially clinicians. The objective of this study was to examine depression, anxiety, quality of life (QOL), and related social psychological factors among young front-line clinicians in high-risk areas during the COVID-19 sporadic epidemic in China and to provide a reference for formulating reasonable countermeasures. Methods: In this cross-sectional study, demographic information, COVID-19-related questions, anxiety (Generalized Anxiety Disorder-7, GAD-7), depression (Patient Health Questionnaire-9, PHQ-9), insomnia (Insomnia Severity Index, ISI), stress (Perceived Stress Scale-10, PSS-10), and QOL (World Health Organization Quality of Life-brief version, WHOQOL-BREF) were collected. Binary logistic regression analysis was used to test the relationships between anxiety and/or depression and other related problems. Multiple linear regression analysis was used to test the relationships among factors influencing QOL. Results: A total of 146 young front-line clinicians were included. The prevalence rates of depression, anxiety, and anxiety-depression comorbidity were 37.7% (95% CI = 29.7-45.6%), 26.0% (95% CI = 18.8-33.2%), and 24.0% (95% CI = 17.0-31.0%), respectively. Severe stress (OR = 1.258, 95% CI = 1.098-1.442, P < 0.01) and insomnia (OR = 1.282, 95% CI = 1.135-1.447, P < 0.01) were positively correlated with depression. Severe stress (OR = 1.487, 95% CI = 1.213-1.823, P < 0.01) and insomnia (OR = 1.131, 95% CI = 1.003-1.274, P < 0.05) were positively correlated with anxiety. Severe stress (OR = 1.532, 95% CI = 1.228-1.912, P < 0.01) was positively correlated with anxiety-depression comorbidity. However, insomnia (OR = 1.081, 95% CI = 0.963-1.214, P > 0.05) was not correlated with anxiety-depression comorbidity. The belief that the vaccine will stop the COVID-19 pandemic (OR = 0.099, 95% CI = 0.014-0.715, P < 0.05) was negatively correlated with anxiety and anxiety-depression comorbidity (OR = 0.101, 95% CI = 0.014-0.744, P < 0.05). Severe stress (B = -0.068, 95% CI = -0.129 to -0.007, P < 0.05) and insomnia (B = -0.127, 95% CI = -0.188 to -0.067, P < 0.01) were negatively correlated with QOL. The belief that the vaccine could provide protection (B = 1.442, 95% CI = 0.253-2.631, P < 0.05) was positively correlated with QOL. Conclusions: The prevalence of depression, anxiety, and even anxiety-depression comorbidity was high among young front-line clinicians in high-risk areas during the COVID-19 sporadic epidemic in China. Various biological and psychological factors as well as COVID-19-related factors were associated with mental health issues and QOL. Psychological intervention should evaluate these related factors and formulate measures for these high-risk groups.

7.
Cell Rep Med ; 3(10): 100752, 2022 10 18.
Article in English | MEDLINE | ID: covidwho-2031746

ABSTRACT

Increasing evidence indicates that gut microbiota may play a key role in vaccination immunity. Here, we investigate whether the human gut microbiota and metabolic function correlate with the BBIBP-CorV vaccine response. A total of 207 participants who received the BBIBP-CorV vaccine are enrolled. The gut microbiome and metabolic functions are investigated using metagenomic sequencing and metabolomic assays. We find that BBIBP-CorV vaccination is accompanied by altered microbiome composition and functional pathways, and the gut microbiome and its functional profiles correlate with the vaccine response. The levels of short-chain fatty acids (SCFAs) are much higher in the high antibody response group compared to the low response group, and several SCFAs display a positive correlation with the antibody response. Our study highlights that the gut microbiome and its function is associated with the BBIBP-CorV vaccine response, providing evidence for further exploration of microbiome modulation to improve COVID-19 vaccine efficacy.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Humans , Gastrointestinal Microbiome/physiology , COVID-19 Vaccines , Antibody Formation , Fatty Acids, Volatile/metabolism
8.
Front Public Health ; 10: 915615, 2022.
Article in English | MEDLINE | ID: covidwho-2022944

ABSTRACT

Purpose: To evaluate the volumetric change of COVID-19 lesions in the lung of patients receiving serial CT imaging for monitoring the evolution of the disease and the response to treatment. Materials and methods: A total of 48 patients, 28 males and 20 females, who were confirmed to have COVID-19 infection and received chest CT examination, were identified. The age range was 21-93 years old, with a mean of 54 ± 18 years. Of them, 33 patients received the first follow-up (F/U) scan, 29 patients received the second F/U scan, and 11 patients received the third F/U scan. The lesion region of interest (ROI) was manually outlined. A two-step registration method, first using the Affine alignment, followed by the non-rigid Demons algorithm, was developed to match the lung areas on the baseline and F/U images. The baseline lesion ROI was mapped to the F/U images using the obtained geometric transformation matrix, and the radiologist outlined the lesion ROI on F/U CT again. Results: The median (interquartile range) lesion volume (cm3) was 30.9 (83.1) at baseline CT exam, 18.3 (43.9) at first F/U, 7.6 (18.9) at second F/U, and 0.6 (19.1) at third F/U, which showed a significant trend of decrease with time. The two-step registration could significantly decrease the mean squared error (MSE) between baseline and F/U images with p < 0.001. The method could match the lung areas and the large vessels inside the lung. When using the mapped baseline ROIs as references, the second-look ROI drawing showed a significantly increased volume, p < 0.05, presumably due to the consideration of all the infected areas at baseline. Conclusion: The results suggest that the registration method can be applied to assist in the evaluation of longitudinal changes of COVID-19 lesions on chest CT.


Subject(s)
COVID-19 , Adult , Aged , Aged, 80 and over , Algorithms , Female , Humans , Lung , Male , Middle Aged , Tomography, X-Ray Computed , Young Adult
9.
Front Immunol ; 13: 964622, 2022.
Article in English | MEDLINE | ID: covidwho-2022748

ABSTRACT

Acute pancreatitis is a common critical and acute gastrointestinal disease worldwide, with an increasing percentage of morbidity. However, the gene expression pattern in peripheral blood has not been fully analyzed. In addition, the mechanism of coronavirus disease 2019 (COVID-19)-induced acute pancreatitis has not been investigated. Here, after bioinformatic analysis with machine-learning methods of the expression data of peripheral blood cells and validation in local patients, two functional gene modules in peripheral blood cells of acute pancreatitis were identified, and S100A6, S100A9, and S100A12 were validated as predictors of severe pancreatitis. Additionally, through a combination analysis of bulk sequencing and single-cell sequencing data of COVID-19 patients, a pivotal subtype of neutrophils with strong activation of the interferon-related pathway was identified as a pivotal peripheral blood cell subtype for COVID-19-induced acute pancreatitis. These results could facilitate the prognostic prediction of acute pancreatitis and research on COVID-19-induced acute pancreatitis.


Subject(s)
COVID-19 , Pancreatitis , Acute Disease , Biomarkers , COVID-19/genetics , Humans , Neutrophils/metabolism , Pancreatitis/metabolism
10.
Comput Struct Biotechnol J ; 20: 5014-5027, 2022.
Article in English | MEDLINE | ID: covidwho-2007642

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has led to a global pandemic. Deep learning (DL) technology and molecular dynamics (MD) simulation are two mainstream computational approaches to investigate the geometric, chemical and structural features of protein and guide the relevant drug design. Despite a large amount of research papers focusing on drug design for SARS-COV-2 using DL architectures, it remains unclear how the binding energy of the protein-protein/ligand complex dynamically evolves which is also vital for drug development. In addition, traditional deep neural networks usually have obvious deficiencies in predicting the interaction sites as protein conformation changes. In this review, we introduce the latest progresses of the DL and DL-based MD simulation approaches in structure-based drug design (SBDD) for SARS-CoV-2 which could address the problems of protein structure and binding prediction, drug virtual screening, molecular docking and complex evolution. Furthermore, the current challenges and future directions of DL-based MD simulation for SBDD are also discussed.

11.
World J Psychiatry ; 12(7): 999-1001, 2022 Jul 19.
Article in English | MEDLINE | ID: covidwho-1997980

ABSTRACT

The article not only successfully evaluated regular physical activities can improve mental well-being during self-isolation and social distancing policies related to the coronavirus disease 2019 (COVID-19), but also concluded that the COVID-19 pandemic may lead to augmented levels of angiotensin-converting enzyme-2. By reading the article of Walid Kamal Abdelbasset, we have some questions and put forward some suggestions on the content of the article.

12.
Front Psychiatry ; 13: 919176, 2022.
Article in English | MEDLINE | ID: covidwho-1993847

ABSTRACT

Objectives: Sleep disturbance and mental health are challenges for healthcare workers (HCWs). Especially during the COVID-19 pandemic, they experienced more severe sleep and mental health problems. However, the association between sleep disturbance and the mental health of HCWs is still controversial. This study aimed to systematically review the relationship by conducting a systematic review and meta-analysis. Method: Two researchers retrieved the literature from Web of Science, PubMed, EMBASE, CINAHL, Psyclnfo, and Cochrane Library from the establishment of the databases until November 20, 2021. We used the New Castle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) to evaluate the risk of bias in prospective research and cross-sectional research, respectively. The major exposure was HCWs' sleep disturbance, and the major outcome was mental health. The correlation coefficients (r), regression coefficients (ß) and odds ratios (OR) of the included studies were integrated. Result: Fifty-nine studies were included for qualitative analysis, of which 30 studies could be combined and entered into quantitative analysis. There were 23 studies during the COVID-19 pandemic among the 59 included studies. The results of the meta-analysis showed that the correlation coefficient between sleep disturbance and mental health was 0.43 (95% CI: 0.39-0.47). HCWs with sleep disturbance had a 3.74 (95% CI: 2.76-5.07) times higher risk of mental health problems than those without sleep disturbance. The correlation coefficient during the COVID-19 epidemic was 0.45 (95% CI: 0.37-0.53), while it was 0.40 (95% CI: 0.36-0.44) during the non-epidemic period. Subgroup analysis compared the OR results in epidemic and non-epidemic periods of COVID-19, which were 4.48 (95% CI: 2.75-5.07) and 3.74 (95% CI: 2.74-7.32), respectively. Conclusion: Sleep disturbance and mental health problems were positively correlated among HCWs. Particularly in the COVID-19 pandemic, more attention should be given to this issue.

13.
Imeta ; : e42, 2022 Aug 05.
Article in English | MEDLINE | ID: covidwho-1976732

ABSTRACT

In China, traditional Chinese medicine (TCM) has been widely used for coronavirus infectious disease 2019 (COVID-19) prevention, treatment, and recovery and has played a part in the battle against the disease. A variety of TCM treatments have been recommended for different stages of COVID-19. But, to the best of our knowledge, a comprehensive database for storing and organizing anti-COVID TCM treatments is still lacking. Herein, we developed TCM2COVID, a manually curated resource of anti-COVID TCM formulas, natural products (NPs), and herbs. The current version of TCM2COVID (1) documents over 280 TCM formulas (including over 300 herbs) with detailed clinical evidence and therapeutic mechanism information; (2) records over 80 NPs with detailed potential therapeutic mechanisms; and (3) launches a useful web server for querying, analyzing and visualizing documented formulas similar to those supplied by the user (formula similarity analysis). In summary, TCM2COVD provides a user-friendly and practical platform for documenting, querying, and browsing anti-COVID TCM treatments, and will help in the development and elucidation of the mechanisms of action of new anti-COVID TCM therapies to support the fight against the COVID-19 epidemic. TCM2COVID is freely available at http://zhangy-lab.cn/tcm2covid/.

14.
Front Public Health ; 10: 929683, 2022.
Article in English | MEDLINE | ID: covidwho-1974695

ABSTRACT

Objective: During the COVID-19 pandemic, the occupational stress of medical staff has been a major issue. This study aimed to suggest a new strategy to identify high-risk factor sets of occupational stress in medical staff using fuzzy-set qualitative comparative analysis (fs-QCA) and provide ideas for the prevention and intervention of occupational stress. Methods: A total of 1,928 medical staff members were surveyed and tested using the Acceptance and Action Questionnaire-II (AAQ-II), Occupational Stress Inventory-Revised edition (OSI-R), and Eysenck Personality Questionnaire-Revised Short Scale (EPQ-RSC). The fs-QCA was used to explore the high-risk factors for occupational stress among medical staff. Results: The psychological strain (PSY) score of the medical staff was 26.8 ± 7.13, and the physical strain (PHS) score was 24.3 ± 6.50. Low psychological flexibility score-introversion-high role overload, introversion-neuroticism-high role overload, and low psychological flexibility score-neuroticism were high-risk factor sets for PSY. Low psychological flexibility score-introversion-high role overload, low psychological flexibility score-introversion-neuroticism, low psychological flexibility score-neuroticism-high role overload, low psychological flexibility score-psychoticism-neuroticism, and psychoticism-neuroticism-high role overload were high-risk factor sets for PHS. Conclusion: There are different combinations of high-risk factors for occupational stress among the medical staff. For occupational stress intervention and psychological counseling, targeted and individualized health intervention measures should be implemented according to specific characteristic combinations of different individuals.


Subject(s)
COVID-19 , Occupational Stress , COVID-19/epidemiology , Humans , Medical Staff , Occupational Stress/psychology , Pandemics , Personality , Workload
15.
Advanced Functional Materials ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-1971206

ABSTRACT

Uncontrolled or chronic inflammation contributes to the pathogenesis of many acute/chronic diseases, such as acute organ injury, COVID‐19, and atherosclerosis. Intrinsically bioactive materials are promising for regulating the response magnitude and duration of inflammation, but their translation remains challenging. Herein, the engineering of a series of inflammation‐resolving materials by rationally integrating different functional modules into a hydrolyzable scaffold is reported. The obtained functional materials can assemble into potent anti‐inflammatory micelles capable of eliminating different types of reactive oxygen species, releasing bioactive molecules, and simultaneously hydrolyzing into water‐soluble and excretable compounds. Cellularly, these micelles effectively inhibit the migration, activation, and production of molecular mediators in inflammatory cells. Benefiting from the small size and high bioactivity, the developed micelles efficiently accumulate in the kidneys of mice with acute kidney injury (AKI) and efficaciously alleviate AKI. Bioactive micelles also demonstrate desirable targeting and superior efficacies in mice with acute liver failure. Mechanistically, inhibition of oxidative damage, attenuation of inflammatory cell infiltration and activation, and promoting resolution of inflammation mainly account for beneficial therapeutic effects of micelles. Moreover, preliminary studies reveal the excellent safety of micelles. Consequently, the bioactive materials represent a new type of efficacious, safe, scalable, and affordable therapy for a broad spectrum of inflammatory diseases. [ FROM AUTHOR] Copyright of Advanced Functional Materials is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

16.
Trends Biotechnol ; 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967179

ABSTRACT

SARS-CoV-2, the causative agent of COVID-19, remains among the main causes of global mortality. Although antigen/antibody-based immunoassays and neutralizing antibodies targeting SARS-CoV-2 have been successfully developed over the past 2 years, they are often inefficient and unreliable for emerging SARS-CoV-2 variants. Novel approaches against SARS-CoV-2 and its variants are therefore urgently needed. Aptamers have been developed for the detection and inhibition of several different viruses such as HIV, influenza viruses, Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV. Aptamers targeting SARS-CoV-2 represent a promising tool in the fight against COVID-19, which is of paramount importance for the current and any future pandemics. This review presents recent advances and future trends in the development of aptamer-based approaches for SARS-CoV-2 diagnosis and treatment.

17.
Frontiers in psychology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1958063

ABSTRACT

Purpose A large body of evidence has revealed that the sudden outbreak of public health emergencies induces dramatic effects on the mental health of the general public. We aimed to investigate the level of anxiety sensitivity and its risk factors in children and adolescents from northwest China during the COVID-19 pandemic lockdown in early 2020. Methods A cross-sectional survey was conducted through the Wenjuanxing platform using a convenience sampling method between 18 and 26 February 2020. The self-designed questionnaire contained sociodemographic characteristics, factors associated with the COVID-19 pandemic, and the Childhood Anxiety Sensitivity Index (CASI) scale. The data from 1,091 valid questionnaires from students aged 9–17 years were analyzed using ANOVA, multiple linear regression, and binary logistic regression. Results The average CASI scores were 11.47 ± 6.631, and 642 students (58.9%) had prominent anxiety sensitivity. Gender, education level, family members participating in anti-COVID-19 work, getting ill and needing medical help during the lockdown, feeling afraid or having heart palpitations on hearing things associated with COVID-19, believing that COVID-19 would have adverse impacts on themselves or their family in the future, and fear of infection were identified as significant factors for elevated levels of anxiety sensitivity (p < 0.05). We established a multiple linear regression model for the anxiety sensitivity score. Risk factors found for anxiety sensitivity in children and adolescents during the COVID-19 lockdown included studying in secondary or high school, becoming ill during the pandemic, feeling afraid or experiencing rapid heartbeat or palpitations on hearing about the COVID-19 pandemic, thinking that COVID-19 would have an adverse impact on themselves or their family in the future, and fear of infection. Conclusions During the COVID-19 pandemic and home quarantine, scores measuring the prevalence of anxiety sensitivity in children and adolescents from northwest China were elevated. We should develop measures that especially target possible risk factors to intervene against and prevent anxiety sensitivity in children and adolescents in both the current and future pandemics.

18.
Front Immunol ; 13: 831194, 2022.
Article in English | MEDLINE | ID: covidwho-1952320

ABSTRACT

Resulting from severe inflammation and cell destruction, COVID-19 patients could develop pulmonary fibrosis (PF), which remains in the convalescent stage. Nevertheless, how immune response participates in the pathogenesis of PF progression is not well defined. To investigate that question, 12 patients with severe COVID-19 were included in the study. Peripheral mononuclear cell (PBMC) samples were collected shortly after their admission and proceeded for single-cell RNA sequencing (scRNA-seq). After 14 days of discharge, the patients were revisited for chest CT scan. PF index (FI) was computed by AI-assisted CT images. Patients were categorized into FIhi and FIlo based on median of FI. By scRNA-seq analysis, our data demonstrated that frequency of CD4+ activated T cells and Treg cells were approximately 3-fold higher in FIhi patients compared with FIlo ones (p < 0.034 for all). By dissecting the differentially expressed genes, we found an overall downregulation of IFN-responsive genes (STAT1, IRF7, ISG15, ISG20, IFIs, and IFITMs) and S100s alarmins (S100A8, S100A9, S100A12, etc.) in all T-cell clusters, and cytotoxicity-related genes (GZMB, PRF1, and GNLY) in CTLs and γδ T cells in the FIhi cohort, compared with FIlo subjects. The GSEA analysis illustrated decreased expression of genes enriched in IFN signaling, innate immune response, adaptive immune response in T cells, NK cells, and monocytes in FIhi patients compared with FIlo ones. In conclusion, these data indicated that the attenuated IFN-responsive genes and their related signaling pathways could be critical for PF progression in COVID-19 patients.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Adaptive Immunity , Humans , Leukocytes , Leukocytes, Mononuclear , Pulmonary Fibrosis/genetics
19.
Mil Med Res ; 9(1): 29, 2022 06 13.
Article in English | MEDLINE | ID: covidwho-1951383
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