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1.
Cell reports ; 2022.
Article in English | EuropePMC | ID: covidwho-1728589

ABSTRACT

Zhang et al. show in vitro cross-species infectivity and neutralization-escape characteristics of 153 SARS-CoV-2 RBD mutants and 11 globally circulating VOC/VOI variants. They reveal an association between enhanced cross-species infection potential and the current cumulative prevalence of mutations, which can inform surveillance and forecasting of SARS-CoV-2 spike mutations.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314175

ABSTRACT

Back ground. Asymptomatic/mildly symptomatic coronavirus disease 2019 (COVID-19) patients produce a considerable amount of virus and transmit severe acute respiratory syndrome virus 2 (SARS-CoV-2) through close contact. Preventing in-hospital transmission of SARS-CoV-2 is challenging, since symptom-based screening protocols may miss asymptomatic/mildly symptomatic patients. In particular, dental health workers (HCWs) are at high risk of exposure, as face-to-face contact and exposure to oral secretions is unavoidable. We report exposure of HCWs during dental procedures on a mild symptomatic COVID-19 patient. Methods. A 32-year old male visited a dental clinic at a tertiary care hospital. He experienced mild cough, which started three days before the dental visit, but did not report his symptom during the entrance screening. He underwent several dental procedures and imaging for orthognathic surgery without wearing a mask. Seven HCWs were closely exposed to the patient during dental procedures that could have generated droplets and aerosols. One HCW had close contact with the patient during radiologic exams, and seven HCWs had casual contact. All HCWs wore particulate filtering respirators with 94% filter capacity and gloves, but none wore eye protection or gowns. The next day, the patient experienced dysgeusia and was diagnosed with COVID-19 with high viral load. Results. All HCWs who had close contact with the patient were quarantined for 14 days, and polymerase chain reaction and antibody tests for SARS-CoV-2 were negative. Conclusion. This exposure event suggests the protective effect of particulate filtering respirators in dental clinics. The appropriate personal protective equipment for routine patient care during COVID-19 pandemic should be established. The appropriate personal protective equipment for routine patient care during COVID-19 pandemic should be established.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325356

ABSTRACT

Background: In critically ill COVID-19 patients, the crucial turning point before critical illness onset (CIO) remain largely unknown, and the combination of baseline risk factors with the turning point during hospitalization was rarely reported. Methods: In this retrospective cohort study, 1150 consecutively admitted patients with confirmed COVID-19 were enrolled, including 296 critical and 854 non-critical patients. We compared the differences of all the clinically tested indicators and their dynamic changes between critical and non-critical patients. Three prediction models were established and validated based on the risk factors at admission, and an online baseline predictive tool was developed. Linear mixed model (LMM) was applied for longitudinal data analysis in 296 critical patients throughout the hospitalization, to predict the likelihood and possible time of critical illness in COVID-19 patients. A crucial turning point, where several indicators will experience a greater and significantly continuous change before CIO, was defined as “burning point” in our study. This point indicates the deterioration of patient’s condition before CIO. Results: We established a novel two-checkpoint system to predict critical illness for COVID-19 patients in which the first checkpoint happened at patient admission was assessed by a baseline prediction model to project the likelihood of critical illness based on the variables selected from random forest and LASSO regression analysis, including age, SOFA score, neutrophil-to-lymphocyte ratio (NLR), D-dimer, lactate dehydrogenase (LDH), International Normalized Ratio (INR), and pneumonia area derived from CT images, which yields an AUC of 0.960 (95% confidence interval, 0.941-0.972) and 0.958 (0.936-0.980) in the training and testing sets, respectively. This model has been translated into a public web-based risk calculator. Furthermore, the second checkpoint (designated as “burning point” in our study) could be identified as early as 5 days preceding the CIO, and 12 ( IQR , 7-17) days after illness onset. Seven most significant and representative “burning point” indicators were SOFA score, NLR, C-reactive protein (CRP), glucose, D-dimer, LDH, and blood urea nitrogen (BUN). Conclusions: With this two-checkpoint prediction system, the deterioration of COVID-19 patients could be early identified and more intensive treatments could be started in advance to reduce the incidence of critical illness.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325355

ABSTRACT

Background: Multiple organ damage and abnormal inflammation caused by COVID-19 have previously been reported in hospitalized patients. It remains unclear whether these patients can return to a healthy individual three months after discharge and whether there are related sequelae.Methods: We followed up 95 severe/critical patients and 51 mild/moderate ones who recovered from COVID-19 and were discharged from hospital for 3 months. For comparison, 28 asymptomatic COVID-19 recovered individuals and 42 uninfected healthy donors (HDs) were included. At the visit, patients were interviewed and subjected to quality-of-life evaluation (St. George respiratory questionnaire [SGRQ]), pulmonary function tests, chest CT imaging, laboratory examination, detection of immune cells, and cytokine profiling.Findings: At three months, all recovered patients tested negative for nucleic acid of SARS-CoV-2, and most were positive for serum SARS-COV-2 IgG, but few were still positive for serum IgM. The SGRQ scores for the quality-of-life were higher in recovered patients, especially those who had had severe/critical disease. Laboratory test revealed that CRP, LDH and D-dimer, three prevalent risk factors for COVID-19 prognosis in the acute phase, did not recover to the level of uninfected HDs in the convalescence. Immune cells virtually returned to normal levels in patients who recovered from COVID-19, but some pro-inflammatory cytokines, especially chemokines and factors related to vascular injury and angiogenesis, did not return to the level of HDs, and this was especially true of severe/critical recovered patients. CT of the lungs showed that ground-glass opacity (GGO) still lingered as the main manifestation, followed by strip-like fibrosis. Artificial intelligence (AI) analysis indicated that the lesions were most prominent in the lower lobe of right lung, and were mainly found in recovered severe/critical individuals. Abnormal lung function was mainly manifested as restrictive ventilation dysfunction and lowered diffusion capacity, which was more pronounced in severe/critical COVID-19 recovered patients. Overall, the recovery status of the patients varied with the severity of the disease.Interpretation: Decreased physical quality of life, respiratory sequelae (restrictive ventilatory dysfunction, diffusion capacity disorder, and chest CT abnormalities), vascular injury and aberrant cytokine profiles still existed three months after discharge, and were more frequent and conspicuous in severe/critical COVID-19 rehabilitation patients compared to their mild/moderate and asymptomatic counterparts.Trial Registration: This project was registered on the Clinical Trials website (No. NCT04456101) Funding: This study was supported in part by the National Natural Science Special Foundation of China (82041018, 81800094), National Major Science and Technology Projects of China (CN):2019ZX09301001, Ministry of Science and Technology of the People's Republic of China (CN):2020YFC0844300, and the Fundamental Research Funds for the Central Universities, HUST: 2020kfyXGYJ011.Declaration of Interests: The authors have no conflict of interest or financial relationships to disclose. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.Ethics Approval Statement: The protocol used in this project has been reviewed and approved by the institutional review boards of Medical Ethics Committee of Wuhan Union Hospital (NO.0271-01). All participants or their surrogates signed informed consent.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324308

ABSTRACT

Background: Coronavirus disease-2019 (COVID-19) is sweeping the globe and the situation is precarious. Aim of our study is to develop and validate a radiomics-based model to predict the short-term prognosis of COVID-19 patients and to improve hospital survival. Methods: : In our multi-center study, a first batch of 148 patients in the training set was used to build prognosis prediction model, and a second batch of 264 patients was assigned as validation set to verify the predictive performance. Patients were divided into two groups (good/poor prognosis) according to the outcome evaluation both on the 14th day after admission. Data were collected at admission involving demographic and epidemiological features, symptoms, laboratory results and CT images. The latter contained direct CT findings and radiomic features. Radiomic scores (Rad-scores) were calculated for each patient by a linear combination of the extracted features with their respective coefficients. Univariable and multivariable Logistic regression analysis were conducted in sequence to select variables for building a nomogram prediction model, which was applied for prognostic evaluation. Results: : We reported that the nomogram scoring system, including age, central/peripheral lesion location in CT findings, C-reactive protein (CRP) and Rad-score, could effectively predict the short-term outcomes of COVID-19 patients with a sensitivity of 81 . 25% and specificity of 87 . 27%. The predictive performance of this model was also validated in the independent validation dataset yielding a sensitivity of 88 . 76%, specificity of 72 . 97% (AUC: 0 . 882). Conclusions: : This radiomics-based model could predict the short-term prognosis of COVID-19 patients and to improve hospital survival.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323695

ABSTRACT

Knowing the residual and future effect of SARS-CoV-2 on recovered COVID-19 patients is critical for optimized long-term patient management. Recent studies focus on the symptoms and clinical indices of recovered patients, but the pathophysiological change is still unclear. To address this question, we examined the metabolomic profiles of recovered asymptomatic (RA), moderate (RM) and severe and critical (RC) patients without previous underlying diseases discharged from the hospital for 3 months, along with laboratory and CT findings. We found that the serum metabolic profiles in recovered COVID-19 patients still conspicuously differed from that in healthy control (HC), especially in the RM, and RC patients. Additionally, these changes bore close relationship with the function of pulmonary, renal, hepatic, microbial and energetic metabolism and inflammation. These findings suggested that RM and RC patients sustained multi-organ and multi-system damage and these patients should be followed up on regular basis for possible organ and system damage.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323542

ABSTRACT

Background: Since December 2019, an infectious disease caused by SARS-CoV-2 has swept through the world and has had a significant impact on dental services. Methods: In this study, from April 21 to April 28, 2020, a questionnaire survey was taken by a self-made questionnaire in order to investigate the impact of the COVID-19 epidemic on the decision-making process for impacted mandibular third molar removal and related clinical teaching. The Wenjuanxing software was used as a survey platform to survey oral clinicians engaged in the extraction of mandibular third molars. ResultsA total of 321 valid questionnaires were returned in this study. Because of the COVID-19 pandemic. The results showed that 22.4% of clinicians were temporarily not performing tooth extractions in outpatient clinics, and 50.2% of clinicians were temporarily not performing impacted tooth extractions. The main reason cited was that “Aerosol-generating high-speed handpieces were not recommended to be used during the pandemic.” During the pandemic, the surgical handpiece with copious saline irrigation was the main method used for bone removal;the hammer-and-chisel method was considered to be too traumatic and posed too high a risk of iatrogenic injury.ConclusionThe implementation of epidemic control measures during the novel COVID-19 pandemic significantly affects clinical decision making regarding impacted mandibular third molar extractions, the main reason cited was the contraindication to using aerosol-generating high-speed handpieces. The hammer and chisel method may represent a valuable surgical application under the requirements for epidemic prevention and control.

8.
Clin Infect Dis ; 73(12): 2228-2239, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1599322

ABSTRACT

BACKGROUND: Elucidation of the molecular mechanisms involved in the pathogenesis of coronavirus disease 2019 (COVID-19) may help to discover therapeutic targets. METHODS: To determine the metabolomic profile of circulating plasma from COVID-19 survivors with pulmonary sequelae 3 months after discharge, a random, outcome-stratified case-control sample was analyzed. We enrolled 103 recovered COVID-19 patients as well as 27 healthy donors, and performed pulmonary function tests, computerized tomography (CT) scans, laboratory examinations, and liquid chromatography-mass spectrometry. RESULTS: Plasma metabolite profiles of COVID-19 survivors with abnormal pulmonary function were different from those of healthy donors or subjects with normal pulmonary function. These alterations were associated with disease severity and mainly involved amino acid and glycerophospholipid metabolic pathways. Furthermore, increased levels of triacylglycerols, phosphatidylcholines, prostaglandin E2, arginine, and decreased levels of betain and adenosine were associated with pulmonary CO diffusing capacity and total lung capacity. The global plasma metabolomic profile differed between subjects with abnormal and normal pulmonary function. CONCLUSIONS: Further metabolite-based analysis may help to identify the mechanisms underlying pulmonary dysfunction in COVID-19 survivors, and provide potential therapeutic targets in the future.


Subject(s)
COVID-19 , Humans , Metabolomics , Patient Discharge , SARS-CoV-2 , Survivors
9.
J Infect Dis ; 224(9): 1473-1488, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522215

ABSTRACT

BACKGROUND: Postdischarge immunity and its correlation with clinical features among patients recovered from coronavirus disease 2019(COVID-19) are poorly described. This prospective cross-sectional study explored the inflammatory profiles and clinical recovery of patients with COVID-19 at 3 months after hospital discharge. METHODS: Patients with COVID-19 discharged from 4 hospitals in Wuhan, recovered asymptomatic patients (APs) from an isolation hotel, and uninfected healthy controls (HCs) were recruited. Viral nucleic acid and antibody detection, laboratory examination, computed tomography, pulmonary function assessment, multiplex cytokine assay, and flow cytometry were performed. RESULTS: The72 age-, sex- and body mass index-matched participants included 19 patients with severe/critical COVID-19 (SPs), 20 patients with mild/moderate COVID-19 (MPs), 16 APs, and 17 HCs. At 3 months after discharge, levels of proinflammatory cytokines and factors related to vascular injury/repair in patients recovered from COVID-19 had not returned to those of the HCs, especially among recovered SPs compared with recovered MPs and APs. These cytokines were significantly correlated with impaired pulmonary function and chest computed tomographic abnormalities. However, levels of immune cells had returned to nearly normal levels and were not significantly correlated with abnormal clinical features. CONCLUSION: Vascular injury, inflammation, and chemotaxis persisted in patients with COVID-19 and were correlated with abnormal clinical features 3 months after discharge, especially in recovered SPs.


Subject(s)
COVID-19/diagnosis , COVID-19/immunology , Cytokines/immunology , Survivors/psychology , Aftercare , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/therapy , China/epidemiology , Cross-Sectional Studies , Humans , Patient Discharge , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Vascular System Injuries
10.
Diagnostics (Basel) ; 11(10)2021 Sep 28.
Article in English | MEDLINE | ID: covidwho-1480621

ABSTRACT

OBJECTIVE: To provide the quantitative volumetric data of the total lung and lobes in inspiration and expiration from healthy adults, and to explore the value of paired inspiratory-expiratory chest CT scan in pulmonary ventilatory function and further explore the influence of each lobe on ventilation. METHODS: A total of 65 adults (29 males and 36 females) with normal clinical pulmonary function test (PFT) and paired inspiratory-expiratory chest CT scan were retrospectively enrolled. The inspiratory and expiratory volumetric indexes of the total lung (TL) and 5 lobes (left upper lobe [LUL], left lower lobe [LLL], right upper lobe [RUL], right middle lobe [RML], and right lower lobe [RLL]) were obtained by Philips IntelliSpace Portal image postprocessing workstation, including inspiratory lung volume (LVin), expiratory lung volume (LVex), volume change (∆LV), and well-aerated lung volume (WAL, lung tissue with CT threshold between -950 and -750 HU in inspiratory scan). Spearman correlation analysis was used to explore the correlation between CT quantitative indexes of the total lung and ventilatory function indexes (including total lung capacity [TLC], residual volume [RV], and force vital capacity [FVC]). Multiple stepwise regression analysis was used to explore the influence of each lobe on ventilation. RESULTS: At end-inspiratory phase, the LVin-TL was 4664.6 (4282.7, 5916.2) mL, the WALTL was 4173 (3639.6, 5250.9) mL; both showed excellent correlation with TLC (LVin-TL: r = 0.890, p < 0.001; WALTL: r = 0.879, p < 0.001). From multiple linear regression analysis with lobar CT indexes as variables, the LVin and WAL of these two lobes, LLL and RUL, showed a significant relationship with TLC. At end-expiratory phase, the LVex-TL was 2325.2 (1969.7, 2722.5) mL with good correlation with RV (r = 0.811, p < 0.001), of which the LVex of RUL and RML had a significant relationship with RV. For the volumetric change within breathing, the ∆LVTL was 2485.6 (2169.8, 3078.1) mL with good correlation with FVC (r = 0.719, p < 0.001), moreover, WALTL showed a better correlation with FVC (r = 0.817, p < 0.001) than that of ∆LVTL. Likewise, there was also a strong association between ∆LV, WAL of these two lobes (LLL and RUL), and FVC. CONCLUSIONS: The quantitative indexes derived from paired inspiratory-expiratory chest CT could reflect the clinical pulmonary ventilatory function, LLL, and RUL give greater impact on ventilation. Thus, the pulmonary functional evaluation needs to be more precise and not limited to the total lung level.

11.
Infect Dis Ther ; 11(1): 145-163, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1479541

ABSTRACT

INTRODUCTION: To assess the long-term consequences of coronavirus disease (COVID-19) among health care workers (HCWs) in China (hereafter surviving HCWs). METHODS: A total of 303 surviving HCWs were included. Lung (pulmonary function test, 6-min walk test [6MWT], chest CT), physical (St. George's Respiratory Questionnaire [SGRQ], Modified Medical Research Council dyspnea scale [mMRC], and Borg scale), and psychiatric functions (Essen Trauma Inventory) were evaluated during the 1-year follow-up. RESULTS: Surviving HCWs had an abnormal diffusion capacity 1 year post-discharge. Participants with a reduced carbon monoxide diffusing capacity (DLCO) comprised 43.48%. The proportion of HCWs with a median 6MWT distance below the lower limit of the normal was 19.4%. An abnormal CT pattern was observed in 37.5% of the HCWs. The SGRQ, mMRC, and Borg scores of surviving HCWs, especially those with critical/severe disease, were significantly higher than those in the normal population. Probable post-traumatic stress disorder (PTSD) was reported in 21.9% of the surviving HCWs. Diffusion capacity impairment was associated with women. Critical/severe illness and nurses were associated with impaired physical function. CONCLUSIONS: Most surviving HCWs, especially female HCWs, still had an abnormal diffusion capacity at 1 year. The physical and psychiatric functions of surviving HCWs were significantly worse than those of the healthy population. Long-term follow-up of pulmonary, physical, and psychiatric functions for surviving HCWs is required.

12.
J Biol Chem ; 297(5): 101315, 2021 11.
Article in English | MEDLINE | ID: covidwho-1472025

ABSTRACT

Coagulopathy is associated with both inflammation and infection, including infections with novel severe acute respiratory syndrome coronavirus-2, the causative agent Coagulopathy is associated with both inflammation and infection, including infection with novel severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19. Clot formation is promoted via cAMP-mediated secretion of von Willebrand factor (vWF), which fine-tunes the process of hemostasis. The exchange protein directly activated by cAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a regulatory role in suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized our EPAC1-null mouse model and revealed increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1 in vitro mimicked the EPAC1-/- phenotype. In addition, EPAC1 regulated tumor necrosis factor-α-triggered vWF secretion from human umbilical vein endothelial cells in a manner dependent upon inflammatory effector molecules PI3K and endothelial nitric oxide synthase. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, both in vivo and in vitro. Our data delineate a novel regulatory role for EPAC1 in vWF secretion and shed light on the potential development of new strategies to control thrombosis during inflammation.


Subject(s)
Endothelial Cells/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Nitric Oxide Synthase Type III/metabolism , Phosphatidylinositol 3-Kinases/metabolism , von Willebrand Factor/metabolism , Animals , COVID-19/metabolism , Disease Models, Animal , Guanine Nucleotide Exchange Factors/deficiency , Guanine Nucleotide Exchange Factors/genetics , Inflammation/metabolism , Mice , Mice, Knockout
13.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166289, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1466061

ABSTRACT

To explore the recovery of renal function in severely ill coronavirus disease (COVID-19) survivors and determine the plasma metabolomic profile of patients with different renal outcomes 3 months after discharge, we included 89 severe COVID-19 survivors who had been discharged from Wuhan Union Hospital for 3 months. All patients had no underlying kidney disease before admission. At patient recruitment, renal function assessment, laboratory examination, chest computed tomography (CT) were performed. Liquid chromatography-mass spectrometry was used to detect metabolites in the plasma. We analyzed the longitudinally change in the estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin-c levels using the CKD-EPI equation and explored the metabolomic differences in patients with different eGFR change patterns from hospitalization to 3 months after discharge. Lung CT showed good recovery; however, the median eGFR significantly decreased at the 3-month follow-up. Among the 89 severely ill COVID-19 patients, 69 (77.5%) showed abnormal eGFR (<90 mL/min per 1.73 m2) at 3 months after discharge. Age (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.08-1.47, p = 0.003), body mass index (OR = 1.97, 95% CI = 1.20-3.22, p = 0.007), and cystatin-c level (OR = 1.22, 95% CI = 1.07-1.39, p = 0.003) at discharge were independent risk factors for post-discharge abnormal eGFR. Plasma metabolomics at the 3-months follow-up revealed that ß-pseudouridine, uridine, and 2-(dimethylamino) guanosine levels gradually increased with an abnormal degree of eGFR. Moreover, the kynurenine pathway in tryptophan metabolism, vitamin B6 metabolism, cysteine and methionine metabolism, and arginine biosynthesis were also perturbed in survivors with abnormal eGFR.


Subject(s)
COVID-19/complications , COVID-19/virology , Energy Metabolism , Glomerular Filtration Rate , Kidney Diseases/etiology , Kidney Diseases/metabolism , SARS-CoV-2 , Aged , COVID-19/diagnosis , Comorbidity , Female , Humans , Kidney Diseases/diagnosis , Kidney Function Tests , Male , Metabolic Networks and Pathways , Metabolome , Metabolomics/methods , Middle Aged , Odds Ratio , Patient Discharge , Severity of Illness Index , Symptom Assessment
14.
Front Immunol ; 12: 744206, 2021.
Article in English | MEDLINE | ID: covidwho-1459508

ABSTRACT

The effects of corticosteroid use on the reactogenicity and immunogenicity of ChAdOx1 nCoV-19 (ChAd) vaccine were evaluated. Healthcare workers (HCWs) who took low-dose corticosteroid agents around the time of the first dose of ChAd (ChAdPd group) were recruited and the reactogenicity and immunogenicity were compared with those of ChAd (ChAd group) and BNT162b2 vaccination (BNT group) of HCWs without corticosteroid exposure. The immunogenicity was measured three weeks after vaccination using quantitative anti-SARS-CoV-2 spike protein (S) antibody electrochemiluminescence immunoassay and interferon gamma (IFN-γ) release assay. A total of 67 HCWs comprising 24 ChAd, 29 BNT, and 14 ChAdPd was included. The median total corticosteroid dose of the ChAdPd group was 30 mg prednisolone equivalents (interquartile range (IQR) 20-71.3 mg). HCWs in the ChAdPd group experienced significantly milder reactogenicity (median total score 7.5, IQR 4.0-18.0) compared to those in the ChAd group (median 23.0, IQR 8.0-43.0, P=0.012) but similar to that in the BNT group (median 5.0, IQR 3.0-9.0, P=0.067). The S antibody concentration of the ChAdPd group (62.4 ± 70.0 U/mL) was higher than that of the ChAd group, though without statistical significance (3.45 ± 57.6 U/mL, P=0.192). The cellular immune response was most robust in the ChAdPd group, with significantly higher IFN-γ concentration (5.363 ± 4.276 IU/mL), compared to the ChAd (0.978 ± 1.181 IU/mL, P=0.002) and BNT (1.656 ± 1.925 IU/mL, P=0.009) groups. This finding suggest that short-term corticosteroid reduces reactogenicity of the first dose of ChAd without hindering immunogenicity.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Adult , Antibodies, Viral/blood , Female , Health Personnel , Humans , Immunity, Cellular , Immunogenicity, Vaccine/drug effects , Interferon-gamma/metabolism , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Vaccination
17.
Cells ; 10(5)2021 04 21.
Article in English | MEDLINE | ID: covidwho-1436054

ABSTRACT

Extracellular vesicles (EVs) refer to a heterogenous population of membrane-bound vesicles that are released by cells under physiological and pathological conditions. The detection of EVs in the majority of the bodily fluids, coupled with their diverse cargo comprising of DNA, RNA, lipids, and proteins, have led to the accumulated interests in leveraging these nanoparticles for diagnostic and therapeutic purposes. In particular, emerging studies have identified enhanced levels of a wide range of specific subclasses of non-coding RNAs (ncRNAs) in EVs, thereby suggesting the existence of highly selective and regulated molecular processes governing the sorting of these RNAs into EVs. Recent studies have also illustrated the functional relevance of these enriched ncRNAs in a variety of human diseases. This review summarizes the current state of knowledge on EV-ncRNAs, as well as their functions and significance in lung infection and injury. As a majority of the studies on EV-ncRNAs in lung diseases have focused on EV-microRNAs, we will particularly highlight the relevance of these molecules in the pathophysiology of these conditions, as well as their potential as novel biomarkers therein. We also outline the current challenges in the EV field amidst the tremendous efforts to propel the clinical utility of EVs for human diseases. The lack of published literature on the functional roles of other EV-ncRNA subtypes may in turn provide new avenues for future research to exploit their feasibility as novel diagnostic and therapeutic targets in human diseases.


Subject(s)
Extracellular Vesicles/physiology , Lung Injury/metabolism , Pneumonia, Bacterial/metabolism , Pneumonia, Viral/metabolism , RNA, Untranslated/physiology , Animals , Biomarkers/metabolism , Humans , Lung/metabolism , Lung/pathology
18.
J Inflamm Res ; 14: 4485-4501, 2021.
Article in English | MEDLINE | ID: covidwho-1410010

ABSTRACT

BACKGROUND: It remains unclear whether discharged COVID-19 patients have fully recovered from severe complications, including the differences in the post-infection metabolomic profiles of patients with different disease severities. METHODS: COVID-19-recovered patients, who had no previous underlying diseases and were discharged from Wuhan Union Hospital for 3 months, and matched healthy controls (HCs) were recruited in this prospective cohort study. We examined the blood biochemical indicators, cytokines, lung computed tomography scans, including 39 HCs, 18 recovered asymptomatic (RAs), 34 recovered moderate (RMs), and 44 recovered severe/ critical patients (RCs). A liquid chromatography-mass spectrometry-based metabolomics approach was employed to profile the global metabolites of fasting plasma of these participants. RESULTS: Clinical data and metabolomic profiles suggested that RAs recovered well, but some clinical indicators and plasma metabolites in RMs and RCs were still abnormal as compared with HCs, such as decreased taurine, succinic acid, hippuric acid, some indoles, and lipid species. The disturbed metabolic pathway mainly involved the tricarboxylic cycle, purine, and glycerophospholipid metabolism. Moreover, metabolite alterations differ between RMs and RCs when compared with HCs. Correlation analysis revealed that many differential metabolites were closely associated with inflammation and the renal, pulmonary, heart, hepatic, and coagulation system functions. CONCLUSION: We uncovered metabolite clusters pathologically relevant to the recovery state in discharged COVID-19 patients which may provide new insights into the pathogenesis of potential organ damage in recovered patients.

19.
J Clin Med ; 9(7)2020 Jul 17.
Article in English | MEDLINE | ID: covidwho-1403634

ABSTRACT

OBJECTIVES: To investigate antibody production in asymptomatic and mild COVID-19 patients. METHODS: Sera from asymptomatic to severe COVID-19 patients were collected. Microneutralization (MN), fluorescence immunoassay (FIA), and enzyme-linked immunosorbent assay (ELISA) were performed. RESULTS: A total of 70 laboratory-confirmed COVID-19 patients were evaluated, including 15 asymptomatic/anosmia, 49 mild symptomatic, and 6 pneumonia patients. The production of the neutralizing antibody was observed in 100% of pneumonia, 93.9% of mild symptomatic, and 80.0% of asymptomatic/anosmia groups. All the patients in the pneumonia group showed high MN titer (≥1:80), while 36.7% of mild symptomatic and 20.0% of asymptomatic/anosmia groups showed high titer (p < 0.001). Anti-SARS-CoV-2 antibodies could be more sensitively detected by FIA IgG (98.8%) and ELISA (97.6%) in overall. For the FIA IgG test, all patients in the pneumonia group exhibited a high COI value (≥15.0), while 89.8% of mild symptomatic and 73.3% of asymptomatic/anosmia groups showed a high value (p = 0.049). For the ELISA test, all patients in the pneumonia group showed a high optical density (OD) ratio (≥3.0), while 65.3% of mild symptomatic and 53.3% of asymptomatic/anosmia groups showed a high ratio (p = 0.006). CONCLUSIONS: Most asymptomatic and mild COVID-19 patients produced the neutralizing antibody, although the titers were lower than pneumonia patients. ELISA and FIA sensitively detected anti-SARS-CoV-2 antibodies.

20.
BMC Med ; 19(1): 163, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1309910

ABSTRACT

BACKGROUND: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China. METHODS: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher's exact test were used to assess the variance between two or more groups where appropriate. RESULTS: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells. CONCLUSION: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19 , Exercise Test , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Adult , COVID-19/epidemiology , COVID-19/immunology , COVID-19/physiopathology , COVID-19/rehabilitation , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/statistics & numerical data , China/epidemiology , Exercise Test/methods , Exercise Test/statistics & numerical data , Female , Follow-Up Studies , Functional Status , Humans , Interleukin-6/blood , Male , Patient Discharge/statistics & numerical data , Severity of Illness Index , Tumor Necrosis Factor-alpha/blood
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