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1.
Cell Rep ; 39(11): 110955, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1866959

ABSTRACT

Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.


Subject(s)
COVID-19 , Heart Injuries , COVID-19/complications , Humans , Inflammation , Proteome , SARS-CoV-2
2.
Journal of Clinical Hepatology ; 38(2):352-358, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-1855929

ABSTRACT

Objective: To investigate whether Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) is more suitable than Nutritional Risk Screening 2002 (NRS-2002) in nutritional risk screening for patients with liver cirrhosis, as well as the applicability of subjective global assessment (SGA) in the nutritional assessment of patients with liver cirrhosis.

3.
Protein Cell ; 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1773029

ABSTRACT

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312626

ABSTRACT

Aims: : Hyperuricemia has attracted increasing attention, however, limited attention has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in COVID-19 patients. Therefore, we aim to explore the SUA levels in COVID-19 patients and the relationship between SUA and the severity of COVID-19. Methods: A case-control study based on 91 cases with COVID-19 and 1:3 age- and sex-matched healthy control subjects (N = 273) were included. We firstly compared the SUA levels and the uric acid/creatinine (UA/Cr) ratio between COVID-19 patients and the healthy controls. Then, we examined the association of the SUA levels and UA/Cr ratios with COVID-19 severity defined according to the fifth edition of China’s Diagnosis and Treatment Guidelines of COVID-19. Results: SUA levels at admission were 2.59% lower, UA/Cr ratios 6.06% lower in COVID-19 patients compared to controls. In sex stratified analysis, SUA and UA/Cr were lower in male COVID-19 patients while only SUA was lower in female COVID-19 patient. Moreover, SUA and UA/Cr values were 4.27% and 8.23% lower in the severe group than in the moderate group among male COVID patients. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent factors associated with lower SUA levels. COVID-19 male patients with low SUA levels at had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05;95% CI:1.11,14.72) at admission. After completion of the first follow-up of the COVID-19 patients within 1–3 weeks after discharge, we found that male patients experienced severe symptoms had significantly lower SUA and UA/Cr ratio levels comparing to moderate patients but no significant difference between different time points. In females, female patients have both SUA and UA/Cr ratio levels lower at discharge than that at admission, however these differences disappear at follow-up exam. Conclusion: COVID-19 patients had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher risk of developing severe symptoms than those with high SUA levels. During the aggravation course of the disease, the level of SUA gradually decreased until discharge. At follow-up exam, the level of SUA is similar to the levels at admission.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325431

ABSTRACT

With the rapidly worldwide spread of Coronavirus disease (COVID-19), it is of great importance to conduct early diagnosis of COVID-19 and predict the time that patients might convert to the severe stage, for designing effective treatment plan and reducing the clinicians' workloads. In this study, we propose a joint classification and regression method to determine whether the patient would develop severe symptoms in the later time, and if yes, predict the possible conversion time that the patient would spend to convert to the severe stage. To do this, the proposed method takes into account 1) the weight for each sample to reduce the outliers' influence and explore the problem of imbalance classification, and 2) the weight for each feature via a sparsity regularization term to remove the redundant features of high-dimensional data and learn the shared information across the classification task and the regression task. To our knowledge, this study is the first work to predict the disease progression and the conversion time, which could help clinicians to deal with the potential severe cases in time or even save the patients' lives. Experimental analysis was conducted on a real data set from two hospitals with 422 chest computed tomography (CT) scans, where 52 cases were converted to severe on average 5.64 days and 34 cases were severe at admission. Results show that our method achieves the best classification (e.g., 85.91% of accuracy) and regression (e.g., 0.462 of the correlation coefficient) performance, compared to all comparison methods. Moreover, our proposed method yields 76.97% of accuracy for predicting the severe cases, 0.524 of the correlation coefficient, and 0.55 days difference for the converted time.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324533

ABSTRACT

SARS-CoV-2 infection causes complicated clinic manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various tissues/organs examined, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Neuronal receptor NRP1 expression showed a significant induction by SARS-CoV-2 in cerebral cortex, which might be responsible for a higher infectivity and consequent inflammatory response. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.

8.
Adv Drug Deliv Rev ; 177: 113928, 2021 10.
Article in English | MEDLINE | ID: covidwho-1355523

ABSTRACT

Infectious diseases continue to inflict a high global disease burden. The consensus is that vaccination is the most effective option against infectious diseases. Oral vaccines have unique advantages in the prevention of global pandemics due to their ease of use, high compliance, low cost, and the ability to induce both systemic and mucosal immune responses. However, challenges of adapting vaccines for oral administration remain significant. Foremost among these are enzymatic and pH-dependent degradation of antigens in the stomach and intestines, the low permeability of mucus barrier, the nonspecific uptake of antigens at the intestinal mucosal site, and the immune suppression result from the elusive immune tolerance mechanisms. Innovative delivery techniques promise great potential for improving the flexibility and efficiency of oral vaccines. A better understanding of the delivery approaches and the immunological mechanisms of oral vaccine delivery systems may provide new scientific insight and tools for developing the next-generation oral vaccine. Here, an overview of the advanced technologies in the field of oral vaccination is proposed, including mucus-penetrating nanoparticle (NP), mucoadhesive delivery vehicles, targeting antigen-presenting cell (APC) nanocarriers and enhanced paracellular delivery strategies and so on. Meanwhile, the mechanisms of delivery vectors interact with mucosal barriers are discussed.


Subject(s)
Drug Delivery Systems , Immunity, Mucosal , Intestinal Mucosa/immunology , Vaccines/administration & dosage , Administration, Oral , Animals , Humans
10.
Front Psychol ; 12: 687928, 2021.
Article in English | MEDLINE | ID: covidwho-1348548

ABSTRACT

The COVID-19 pandemic not only threatens people's physical health, but also affects their mental health in the long term. Although people had returned to work and school, they are closely monitoring the development of the epidemic and taking preventive measures. This study attempted to examine the relationship between media exposure, sense of coherence (SOC) and mental health, and the moderating effect of media exposure in college students after returning to school. In the present study, we conducted a cross sectional survey on 424 college students returning to school around May 2020. Self-report questionnaires were used to assess media exposure scale, SOC, depression, anxiety and stress. Correlation and moderation analysis was conducted. The results showed that (1) negative epidemic information exposure, rather than positive epidemic information exposure, was significantly associated with depression, anxiety, and stress. (2) SOC was also associated with depression, anxiety, and stress. (3) The effect of SOC on depression was modified by negative epidemic information exposure. With the increase of negative epidemic information exposure, the predictive effect of SOC on depression is increasing gradually. These findings demonstrated that negative epidemic information exposure was associated with an increased psychological distress in the sample. A high SOC played a certain protective role in the adaptation of college students in the post-epidemic period. It is important to find more ways to increase the colleges' SOC level and avoid negative information exposure.

11.
Stroke Vasc Neurol ; 5(3): 279-284, 2020 09.
Article in English | MEDLINE | ID: covidwho-1318202

ABSTRACT

BACKGROUND AND PURPOSE: COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19. Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection. MATERIALS AND METHODS: Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed. Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared. RESULTS: Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage. COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05). In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001). Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died. The other four patients received anticoagulant treatment with enoxaparin and 2 of them died. As of 24 March 2020, six patients with CVD died (54.5%). CONCLUSION: Acute CVD is not uncommon in COVID-19. Our findings suggest that older patients with risk factors are more likely to develop CVD. The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.


Subject(s)
Betacoronavirus/pathogenicity , Cerebrovascular Disorders/virology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Acute Disease , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19 , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/mortality , China , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Treatment Outcome
12.
Stroke Vasc Neurol ; 5(2): 146-151, 2020 06.
Article in English | MEDLINE | ID: covidwho-1318197

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a pandemic disease globally. Although COVID-19 directly invades lungs, it also involves the nervous system. Therefore, patients with nervous system involvement as the presenting symptoms in the early stage of infection may easily be misdiagnosed and their treatment delayed. They become silent contagious sources or 'virus spreaders'. In order to help neurologists to better understand the occurrence, development and prognosis, we have developed this consensus of prevention and management of COVID-19. It can also assist other healthcare providers to be familiar with and recognise COVID-19 in their evaluation of patients in the clinic and hospital environment.


Subject(s)
Betacoronavirus/pathogenicity , Central Nervous System Infections/therapy , Central Nervous System/virology , Clinical Laboratory Techniques/standards , Coronavirus Infections/therapy , Neurologists/standards , Pneumonia, Viral/therapy , COVID-19 , COVID-19 Testing , Central Nervous System/physiopathology , Central Nervous System Infections/diagnosis , Central Nervous System Infections/physiopathology , Central Nervous System Infections/virology , Consensus , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Early Diagnosis , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Predictive Value of Tests , Prognosis , SARS-CoV-2
13.
BMC Endocr Disord ; 21(1): 97, 2021 May 08.
Article in English | MEDLINE | ID: covidwho-1219368

ABSTRACT

AIMS: Hyperuricemia has attracted increasing attention. However, limited concern has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in patients with COVID-19. Therefore, we aim to explore whether patients with COVID-19 had SUA lower than normal and the relationship of SUA and the severity of COVID-19. METHODS: This was a case-control study based on 91 cases with COVID-19 and 273 age- and sex-matched healthy control subjects. We first compared SUA levels and uric acid/creatinine (UA/Cr) ratio between patients with COVID-19 and the healthy controls. Then, we examined the association of SUA levels and UA/Cr ratios with COVID-19 severity in COVID-19 cases only, defined according to the fifth edition of China's Diagnosis and Treatment Guidelines of COVID-19. RESULTS: SUA levels in patients with COVID-19 were 2.59% lower, UA/Cr ratios 6.06% lower at admission compared with healthy controls. In sex stratified analysis, levels of SUA and UA/Cr were lower in male patients with COVID-19 while only level of SUA was lower in female patients with COVID-19. Moreover, SUA and UA/Cr values were 4.27 and 8.23% lower in the severe group than that in the moderate group among male COVID-19 patients. Bivariate and partial correlations analysis showed negative correlations between SUA or UA/Cr ratio and COVID-19 after adjusting for age, sex, BMI and eGFR. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent risk factors associated with lower SUA levels. Male patients with COVID-19 accompanied by low SUA levels had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11, 14.72) at admission. Comparing SUA and UA/Cr ratio at three time points (admission, discharge, and follow-up), we found that male patients experienced severe symptoms had lower SUA and UA/Cr ratio levels comparing to moderate patients, but no significant difference between three time points. On the contrary, female patients had lower SUA and UA/Cr ratio at discharge than those at admission, but no significant difference of SUA and UA/Cr ratio between moderate and severe group. CONCLUSION: Patients with COVID-19 had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher crude risk of developing severe symptoms than those with high SUA levels. During disease aggravation, the level of SUA gradually decreased until discharge. At the follow-up exam, the level of SUA was similar to the levels at admission.


Subject(s)
COVID-19/blood , SARS-CoV-2 , Uric Acid/blood , Adult , Aged , Body Mass Index , Case-Control Studies , Creatinine/blood , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Risk Factors , Severity of Illness Index , Sex Factors
14.
Front Pharmacol ; 12: 587816, 2021.
Article in English | MEDLINE | ID: covidwho-1172974

ABSTRACT

Background: Coronavirus disease- (COVID-19-) related renal function abnormality is associated with poor prognosis. However, the clinical significance of dynamic changes in renal function indicators has not been studied, and no studies have evaluated the renal function in COVID-19 patients by cystatin C. Objective: This study aimed to evaluate the effect of abnormal renal function on admission on prognosis of COVID-19 patients and the prognostic value of various renal function indicators. Methods: A total of 1,764 COVID-19 patients without a history of chronic kidney disease were categorized into two groups, an elevated cystatin C group and a normal cystatin C group, based on the results of renal function tests on admission. The clinical characteristics were compared between the two groups, and logistic or Cox regression analyses were performed to explore the associations between elevated cystatin C/serum creatinine levels and disease severity and survival. We also performed receiver operating characteristic (ROC) curve, Kaplan-Meier survival, and curve fitting analyses. Results: When adjusted for several significant clinical variables, elevated cystatin C levels on admission were independent predictors of disease severity (p < 0.001), and elevated creatinine levels were independent predictors of death (p = 0.020). Additionally, the ROC curve analysis shows that elevated cystatin C levels [area under the curve (AUC): 0.656] have a better predictive value for disease severity than elevated creatinine levels (AUC: 0.540). The survival curves of patients with elevated cystatin C/creatinine levels show a sharper decline than those of patients with normal cystatin C/creatinine levels (p < 0.001). The curve fitting analysis revealed that, compared to the flat curves of cystatin C and creatinine levels for patients who survived, the curves for patients who died kept rising, and cystatin C levels rose above the normal range earlier than creatinine. Conclusions: Elevated cystatin C, which occurs earlier than serum creatinine, is useful for the early detection of renal function abnormality and might have better predictive value for disease severity in COVID-19 patients, while elevated serum creatinine may have a better predictive value for risks of death.

15.
ESC Heart Fail ; 8(1): 644-651, 2021 02.
Article in English | MEDLINE | ID: covidwho-1064351

ABSTRACT

AIMS: Many studies have explored the clinical characteristics of patients with coronavirus disease (COVID-19), especially patients with cardiovascular disease. However, associated mechanisms and markers remain to be further investigated. This study aimed to investigate the effect of α-hydroxybutyrate dehydrogenase (α-HBDH) levels on disease progression and prognosis of patients with COVID-19. METHODS AND RESULTS: One thousand seven hundred and fifty-one patients from the Leishenshan hospital in Wuhan were divided into elevated and normal groups by α-HBDH level, and the clinical information between the two groups was compared retrospectively. The main outcome evaluation criteria included in-hospital death and disease severity. Univariate and multivariate regression analyses, survival curves, logistic regression, and receiver operating characteristic curve models were performed to explore the relationship between elevated α-HBDH and the two outcomes. Besides, curve fitting analyses were conducted to analyse the relationship between computed tomography score and survival. Among 1751 patients with confirmed COVID-19, 15 patients (0.87%) died. The mean (SD) age of patients was 58 years in normal α-HBDH group and 66 years in elevated α-HBDH group (P < 0.001). The mortality during hospitalization was 0.26% (4 of 1559) for patients with normal α-HBDH levels and 5.73% (11 of 192) for those with elevated α-HBDH levels (P < 0.001). Multivariate Cox analysis confirmed an association between elevated α-HBDH levels and higher risk of in-hospital mortality [hazard ratio: 4.411, 95% confidence interval (95% CI), 1.127-17.260; P = 0.033]. Multivariate logistic regression for disease severity and α-HBDH levels showed significant difference between both groups (odds ratio = 3.759; 95% CI, 1.895-7.455; P < 0.001). Kaplan-Meier curves also illustrated the survival difference between normal and elevated α-HBDH patients (P < 0.001). CONCLUSIONS: Our study found that serum α-HBDH is an independent risk factor for in-hospital mortality and disease severity among COVID-19 patients. α-HBDH assessment may aid clinicians in identifying high-risk individuals among COVID-19 patients.


Subject(s)
COVID-19/diagnosis , Hydroxybutyrate Dehydrogenase/blood , Aged , COVID-19/blood , COVID-19/enzymology , COVID-19/mortality , China/epidemiology , Disease Progression , Hospital Mortality , Humans , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Severity of Illness Index
16.
Sci China Mater ; 64(3): 739-747, 2021.
Article in English | MEDLINE | ID: covidwho-1060838

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread and caused a severe global pandemic. Because no specific drugs are available for COVID-19 and few vaccines are available for SARS-CoV-2, accurate and rapid diagnosis of COVID-19 has been the most crucial measure to control this pandemic. Here, we developed a portable bifunctional electrical detector based on graphene fieldeffect transistors for SARS-CoV-2 through either nucleic acid hybridization or antigen-antibody protein interaction, with ultra-low limits of detection of ~0.1 and ~1 fg mL-1 in phosphate buffer saline, respectively. We validated our method by assessment of RNA extracts from the oropharyngeal swabs of ten COVID-19 patients and eight healthy subjects, and the IgM/IgG antibodies from serum specimens of six COVID-19 patients and three healthy subjects. Here we show that the diagnostic results are in excellent agreement with the findings of polymerase chain reaction-based optical methods; they also exhibit rapid detection speed (~10 min for nucleic acid detection and ~5 min for immunoassay). Therefore, our assay provides an efficient, accurate tool for high-throughput point-of-care testing. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at 10.1007/s40843-020-1577-y.

17.
Front Public Health ; 8: 596168, 2020.
Article in English | MEDLINE | ID: covidwho-1055005

ABSTRACT

Background: Six months since the outbreak of coronavirus disease (COVID-19), the pandemic continues to grow worldwide, although the outbreak in Wuhan, the worst-hit area, has been controlled. Thus, based on the clinical experience in Wuhan, we hypothesized that there is a relationship between the patient's CO2 levels and prognosis. Methods: COVID-19 patients' information was retrospectively collected from medical records at the Leishenshan Hospital, Wuhan. Logistic and Cox regression analyses were conducted to determine the correlation between decreased CO2 levels and disease severity or mortality risk. The Kaplan-Meier curve analysis was coupled with the log-rank test to understand COVID-19 progression in patients with decreased CO2 levels. Curve fitting was used to confirm the correlation between computed tomography scores and CO2 levels. Results: Cox regression analysis showed that the mortality risk of COVID-19 patients correlated with decreased CO2 levels. The adjusted hazard ratios for decreased CO2 levels in COVID-19 patients were 8.710 [95% confidence interval (CI): 2.773-27.365, P < 0.001], and 4.754 (95% CI: 1.380-16.370, P = 0.013). The adjusted odds ratio was 0.950 (95% CI: 0.431-2.094, P = 0.900). The Kaplan-Meier survival curves demonstrated that patients with decreased CO2 levels had a higher risk of mortality. Conclusions: Decreased CO2 levels increased the mortality risk of COVID-19 patients, which might be caused by hyperventilation during mechanical ventilation. This finding provides important insights for clinical treatment recommendations.


Subject(s)
COVID-19/blood , Carbon Dioxide/blood , Hyperventilation/diagnosis , Respiration, Artificial/adverse effects , Aged , Biomarkers/blood , Blood Chemical Analysis , Blood Coagulation Tests , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Hyperventilation/etiology , Kaplan-Meier Estimate , Male , Middle Aged , Pneumonia, Viral/blood , Proportional Hazards Models , Retrospective Studies , Risk Factors
18.
Cell Res ; 30(12): 1078-1087, 2020 12.
Article in English | MEDLINE | ID: covidwho-912896

ABSTRACT

Silent hypoxia has emerged as a unique feature of coronavirus disease 2019 (COVID-19). In this study, we show that mucins are accumulated in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients and are upregulated in the lungs of severe respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected mice and macaques. We find that induction of either interferon (IFN)-ß or IFN-γ upon SARS-CoV-2 infection results in activation of aryl hydrocarbon receptor (AhR) signaling through an IDO-Kyn-dependent pathway, leading to transcriptional upregulation of the expression of mucins, both the secreted and membrane-bound, in alveolar epithelial cells. Consequently, accumulated alveolar mucus affects the blood-gas barrier, thus inducing hypoxia and diminishing lung capacity, which can be reversed by blocking AhR activity. These findings potentially explain the silent hypoxia formation in COVID-19 patients, and suggest a possible intervention strategy by targeting the AhR pathway.


Subject(s)
Interferons/metabolism , Mucus/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Animals , COVID-19/pathology , COVID-19/virology , Cell Line , Epithelial Cells/cytology , Epithelial Cells/metabolism , Epithelial Cells/virology , Humans , Hypoxia , Interferon-beta/pharmacology , Interferon-gamma/pharmacology , Lung/metabolism , Lung/pathology , Macaca , Mice , Mice, Inbred ICR , Mice, Transgenic , Mucins/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Signal Transduction , Up-Regulation/drug effects
19.
Med Image Anal ; 67: 101824, 2021 01.
Article in English | MEDLINE | ID: covidwho-888729

ABSTRACT

With the rapidly worldwide spread of Coronavirus disease (COVID-19), it is of great importance to conduct early diagnosis of COVID-19 and predict the conversion time that patients possibly convert to the severe stage, for designing effective treatment plans and reducing the clinicians' workloads. In this study, we propose a joint classification and regression method to determine whether the patient would develop severe symptoms in the later time formulated as a classification task, and if yes, the conversion time will be predicted formulated as a classification task. To do this, the proposed method takes into account 1) the weight for each sample to reduce the outliers' influence and explore the problem of imbalance classification, and 2) the weight for each feature via a sparsity regularization term to remove the redundant features of the high-dimensional data and learn the shared information across two tasks, i.e., the classification and the regression. To our knowledge, this study is the first work to jointly predict the disease progression and the conversion time, which could help clinicians to deal with the potential severe cases in time or even save the patients' lives. Experimental analysis was conducted on a real data set from two hospitals with 408 chest computed tomography (CT) scans. Results show that our method achieves the best classification (e.g., 85.91% of accuracy) and regression (e.g., 0.462 of the correlation coefficient) performance, compared to all comparison methods. Moreover, our proposed method yields 76.97% of accuracy for predicting the severe cases, 0.524 of the correlation coefficient, and 0.55 days difference for the conversion time.


Subject(s)
COVID-19/classification , COVID-19/diagnostic imaging , Pneumonia, Viral/classification , Pneumonia, Viral/diagnostic imaging , Tomography, X-Ray Computed/methods , Disease Progression , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Radiographic Image Interpretation, Computer-Assisted , Radiography, Thoracic , SARS-CoV-2 , Severity of Illness Index , Time Factors
20.
Int J Med Sci ; 17(16): 2468-2476, 2020.
Article in English | MEDLINE | ID: covidwho-827890

ABSTRACT

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/etiology , Coronavirus Infections/mortality , Pneumonia, Viral/etiology , Pneumonia, Viral/mortality , Procalcitonin/blood , Aged , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , COVID-19 , China/epidemiology , Comorbidity , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Disease Progression , Female , Hospitalization , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Prognosis , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
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