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1.
Front Cell Infect Microbiol ; 12: 807332, 2022.
Article in English | MEDLINE | ID: covidwho-1753361

ABSTRACT

In the early stage of coronavirus disease 2019 (COVID-19), most cases are identified as mild or moderate illnesses. Approximately 20% of hospitalised patients become severe or critical at the middle or late stage of the disease. The predictors and risk factors for prognosis in those with mild or moderate disease remain to be determined. Of 694 patients with COVID-19, 231 patients with mild or moderate disease, who were hospitalised at 10 hospitals in Wenzhou and nearby counties in China, were enrolled in this retrospective study from 17 January to 20 March 2020. The outcomes of these patients included progression from mild/moderate illness to severe or critical conditions. Among the 231 patients, 49 (21.2%) had a poor prognosis in the hospital. Multivariate logistic regression analysis showed that higher inflammation/coagulopathy/immunology responsive index (ICIRI=[c-reactive protein × fibrinogen × D-dimer]/CD8 T cell count) on admission (OR=345.151, 95% CI=23.014-5176.318) was associated with increased odds ratios for poor prognosis. The area under the receiver operating characteristic curve for ICIRI predicting severe and critical condition progression was 0.65 (95% CI=0.519-0.782) and 0.80 (95% CI=0.647-0.954), with cut-off values of 870.83 and 535.44, respectively. Conversely, age, sex, comorbidity, neutrophil/lymphocyte ratio, CD8 T cell count, and c-reactive protein, fibrinogen, and D-dimer levels alone at admission were not good predictors of poor prognosis in patients with mild or moderate COVID-19. At admission, a novel index, ICIRI, tends to be the most promising predictor of COVID-19 progression from mild or moderate illness to severe or critical conditions.


Subject(s)
Blood Coagulation Disorders/virology , COVID-19 , Inflammation/virology , C-Reactive Protein , CD8-Positive T-Lymphocytes/immunology , COVID-19/complications , COVID-19/diagnosis , COVID-19/immunology , Fibrin Fibrinogen Degradation Products , Fibrinogen , Humans , ROC Curve , Retrospective Studies
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315298

ABSTRACT

Background: To develop and validate a risk-scoring model for predicting severe COVID-19 at presentation. Methods: Entire patients with COVID-19 in three cities in Zhejiang, China from December 2019 to February 2020 were analyzed retrospectively. The risk-scoring model was developed with nomogram using multivariate logistic regression and externally validated by the patients from two other cities near Wenzhou. Findings: Severe COVID-19 was detected 58 out of 488 (11·9%) eligible patients in the primary cohort and 24 out of 153 (15·7%) in the validation cohort. The sex (OR 4·11, 95% CI 1·38 to 14·05), body mass index >25 kg/m2 (OR 6·14, 95% CI 2·05 to 21·29), hypertension (OR 4·97, 95% CI 1·73 to 15·37), neutrophil/lymphocyte ratio (3-6) (OR 8·04, 95% CI 2·51 to 29·52), albumin (35-40) g/L (OR 37·96, 95% CI 5·49 to 825·34) and platelets >300×109/L (OR 6·76, 95% CI 1·55 to 32·47) were independent predictors of severe COVID-19. The risk-scoring model-PAINTS performed excellent discrimination with AUC 0·98, 95% CI 0·96 to 1·00 in the primary cohort and AUC 0·78 (95% CI, 0·67 to 0·89) in the validation cohort. Interpretation: PAINTS score may guide clinical decision-making efficiently and allocate limited medical resources reasonably. Funding: The National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology (CN) [2020ZX09201002];Wenzhou Science and Technology Key Problem Program [ZY2020001];The Primary Research and Development Plan of Zhejiang Province [2019C03011] and the Natural Science Foundation of Zhejiang Province [LQ20H150002].Declaration of Interest: None to declare. Ethical Approval: The study was conducted under the amended Declaration of Helsinki and approved by the Institutional Review Board (IRB) of Wenzhou Medical University (No.2020-002). The written consent was waived by the Institutional Review Board (IRB) of Wenzhou Medical University (No.2020-002)

3.
Clin Immunol ; 232: 108852, 2021 11.
Article in English | MEDLINE | ID: covidwho-1401324

ABSTRACT

BACKGROUND: The majority of the coronavirus disease 2019 (COVID-19) non-survivors meet the criteria for disseminated intravascular coagulation (DIC). Although timely monitoring of clotting hemorrhagic development during the natural course of COVID-19 is critical for understanding pathogenesis, diagnosis, and treatment of the disease, however, limited data are available on the dynamic processes of inflammation/coagulopathy/fibrinolysis (ICF). METHODS: We monitored the dynamic progression of ICF in patients with moderate COVID-19. Out of 694 COVID-19 inpatients from 10 hospitals in Wenzhou, China, we selected 293 adult patients without comorbidities. These patients were divided into different daily cohorts according to the COVID-19 onset-time. Furthermore, data of 223 COVID-19 patients with comorbidities and 22 critical cases were analyzed. Retrospective data were extracted from electronic medical records. RESULTS: The virus-induced damages to pre-hospitalization patients triggered two ICF fluctuations during the 14-day course of the disease. C-reactive protein (CRP), fibrinogen, and D-dimer levels increased and peaked at day 5 (D) 5 and D9 during the 1st and 2nd fluctuations, respectively. The ICF activities were higher during the 2nd fluctuation. Although 12-day medication returned high CRP concentrations to normal and blocked fibrinogen increase, the D-dimer levels remained high on days 17 ±â€¯2 and 23 ±â€¯2 days of the COVID-19 course. Notably, although the oxygenation index, prothrombin time and activated partial thromboplastin time were within the normal range in critical COVID-19 patients at administration, 86% of these patients had a D-dimer level > 500 µg/L. CONCLUSION: COVID-19 is linked with chronic DIC, which could be responsible for the progression of the disease. Understanding and monitoring ICF progression during COVID-19 can help clinicians in identifying the stage of the disease quickly and accurately and administering suitable treatment.


Subject(s)
Blood Coagulation/physiology , COVID-19/complications , Fibrinolysis/physiology , Inflammation/etiology , Inflammation/virology , Adult , Anticoagulants/pharmacology , Blood Coagulation/drug effects , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/metabolism , Blood Coagulation Disorders/pathology , Blood Coagulation Disorders/virology , COVID-19/metabolism , COVID-19/pathology , China , Disease Progression , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/metabolism , Disseminated Intravascular Coagulation/pathology , Disseminated Intravascular Coagulation/virology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Hemorrhage/etiology , Hemorrhage/pathology , Hemorrhage/virology , Humans , Inflammation/pathology , Male , Middle Aged , Prothrombin Time , SARS-CoV-2/pathogenicity
4.
Comput Struct Biotechnol J ; 19: 1863-1873, 2021.
Article in English | MEDLINE | ID: covidwho-1171610

ABSTRACT

Metabolic profiling in COVID-19 patients has been associated with disease severity, but there is no report on sex-specific metabolic changes in discharged survivors. Herein we used an integrated approach of LC-MS-and GC-MS-based untargeted metabolomics to analyze plasma metabolic characteristics in men and women with non-severe COVID-19 at both acute period and 30 days after discharge. The results demonstrate that metabolic alterations in plasma of COVID-19 patients during the recovery and rehabilitation process were presented in a sex specific manner. Overall, the levels of most metabolites were increased in COVID-19 patients after the cure relative to acute period. The major plasma metabolic changes were identified including fatty acids in men and glycerophosphocholines and carbohydrates in women. In addition, we found that women had shorter length of hospitalization than men and metabolic characteristics may contribute to predict the duration from positive to negative in non-severe COVID-19 patients. Collectively, this study shed light on sex-specific metabolic shifts in non-severe COVID-19 patients during the recovery process, suggesting a sex bias in prognostic and therapeutic evaluations based on metabolic profiling.

5.
Front Cell Infect Microbiol ; 11: 632490, 2021.
Article in English | MEDLINE | ID: covidwho-1156114

ABSTRACT

The novel coronavirus SARS-CoV-2 (causing the disease COVID-19) has caused a highly transmissible and ongoing pandemic worldwide. Due to its rapid development, next-generation sequencing plays vital roles in many aspects. Here, we summarize the current knowledge on the origin and human transmission of SARS-CoV-2 based on NGS analysis. The ACE2 expression levels in various human tissues and relevant cells were compared to provide insights into the mechanism of SAS-CoV-2 infection. Gut microbiota dysbiosis observed by metagenome sequencing and the immunogenetics of COVID-19 patients according to single-cell sequencing analysis were also highlighted. Overall, the application of these sequencing techniques could be meaningful for finding novel intermediate SARS-CoV-2 hosts to block interspecies transmission. This information will further benefit SARS-CoV-2 diagnostic development and new therapeutic target discovery. The extensive application of NGS will provide powerful support for our fight against future public health emergencies.


Subject(s)
COVID-19/epidemiology , High-Throughput Nucleotide Sequencing/methods , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/microbiology , COVID-19/transmission , COVID-19/virology , Dysbiosis/virology , Gastrointestinal Microbiome , Humans , Metagenome , Pandemics
6.
PLoS Pathog ; 17(3): e1009420, 2021 03.
Article in English | MEDLINE | ID: covidwho-1154087

ABSTRACT

To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8+ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8+ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8+ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.


Subject(s)
Aging/immunology , COVID-19/immunology , Lymphocytes/immunology , SARS-CoV-2/immunology , Sex Characteristics , Adolescent , Adult , Age Factors , Aged , Aging/pathology , COVID-19/pathology , Female , Humans , Lymphocyte Count , Lymphocytes/pathology , Male , Middle Aged , Sex Factors
7.
Aging (Albany NY) ; 13(6): 7713-7722, 2021 03 10.
Article in English | MEDLINE | ID: covidwho-1134586

ABSTRACT

If age boundaries are arbitrarily or roughly defined, age-related analyses can result in questionable findings. Here, we aimed to delineate the uniquely age-dependent immune features of coronavirus disease 2019 (COVID-19) in a retrospective study of 447 patients, stratified according to age distributions of COVID-19 morbidity statistics into well-defined age-cohorts (2-25y, 26-38y, 39-57y, 58-68y, and 69-79y). Age-dependent susceptibilities and severities of the disease were observed in COVID-19 patients. A comparison of the lymphocyte counts among the five age-groups indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection led to age-dependent lymphopenia. Among the lymphocyte subsets, the CD8+ T cell count alone was significantly and age-dependently decreased (520, 385, 320, 172, and 139 n/µl in the five age-groups, respectively). In contrast, the CD4+ T cell, B cell, and natural killer cell counts did not differ among age-cohorts. Age and CD8+ T cell counts (r=‒0.435, p<0.0001) were negatively correlated in COVID-19 patients. Moreover, SARS-CoV-2 infection age-dependently increased the plasma C-reactive protein concentrations (2.0, 5.0, 9.0, 11.6, and 36.1 mg/L in the five age-groups, respectively). These findings can be used to elucidate the role of CD8+ T cells in age-related pathogenesis and to help develop therapeutic strategies for COVID-19.


Subject(s)
Age Distribution , CD3 Complex/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/complications , Lymphopenia/complications , Patient Admission , Adolescent , Adult , Aged , COVID-19/virology , Child , Child, Preschool , Cohort Studies , Female , Humans , Lymphocyte Count , Lymphopenia/immunology , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Young Adult
8.
Neuropsychiatr Dis Treat ; 16: 2661-2667, 2020.
Article in English | MEDLINE | ID: covidwho-954302

ABSTRACT

OBJECTIVE: The WHO has upgraded the status of coronavirus disease 2019 (COVID-19) from epidemic to global pandemic. The psychometric properties aspects of COVID-19 patients without comorbidities in the short term after discharge have not been reported. In this study, the Short Form 36 (SF-36) was used to evaluate the psychometric properties and to find relevant risk factors. METHODS: The study was conducted in seven hospitals from January 2020 to April 2020. The SF-36 questionnaire was administered one month after discharge. Univariate analysis and multivariate regression model were used to analyze the risk factors of psychometric properties impairment. RESULTS: In univariate analysis of independent risk factors, according to the comparison of whether the duration of positive nucleic acid was greater than 20 days, the positive nucleic acid duration was independently related to the decreased role-emotional value [100, IQR (66-100) vs 100, IQR (0, 100); p = 0.0156]. In addition, multivariable linear regression model showed that male sex and positive nucleic acid duration were related to decreased role-emotional value (p = 0.03< 0.05; p = 0.01< 0.05, respectively). Mental health was associated with age (p= 0.0435). Subsequently, we divided into three subgroups: less than seven days, 7 to 14 days and more than 14 days according to the positive nucleic acid duration. The results revealed that there were significant differences in the vitality value and mental health value of patients aged 46 to 69 in the subgroup where the positive nucleic acid duration longer than 14 days (p= 0.0472; p= 0.0311< 0.05, respectively). Similarly, there are also significant differences in role-emotional value in different genders (p= 0.0316). CONCLUSION: The study described the psychometric properties of COVID-19 patients without comorbidities shortly after discharge. Risk factors for psychometric properties damage included age, male sex, and nucleic acid duration.

10.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1492

ABSTRACT

Background: Timely and accurately identification of thrombotic complications seems to become an important issue in patients suffering from coronavirus disease 2

11.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-738

ABSTRACT

Background: This study aimed to establish an effective diagnostic nomogram for suspected SARS-CoV-2 pneumonia patients. br br Methods: We used the LASSO aggre

12.
Diabetes Res Clin Pract ; 168: 108381, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-728512

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) has become a recognized worldwide pandemic. Researchers now know that mortality from COVID-19 can be reduced through early prevention measures. This retrospective, multi-centered study of 293 COVID-19 patients without diabetes explores the association between fasting blood glucose (FBG) levels and the risk of COVID-19 disease progression, with the goal of providing clinical evidence for glycemic targets in patients. METHODS: The multivariate stepwise binary logistic regression analysis was used to test the dose-response effects of FBG levels on the risk of severe and critical condition in COVID-19 patients. RESULTS: FBG levels were plotted in quintiles with set at <4.74, 4.74-5.21, 5.21-5.78, 5.78-7.05, and ≧7.05 mmol/L. The constituent ratio of severe or critical cases in each FBG quintile was 20.7%, 1.7%, 13.8%, 27.1%, and 67.2%, respectively (P < 0.0001). When the second quintile was used as the reference, the adjusted odds ratios (AORs) (95%CI) for the risk of severe/critical condition in COVID-19 was 25.33 (2.77, 231.64), 1.00 (Reference), 3.13 (0.33, 29.67), 10.59 (1.23, 91.24), 38.93 (4.36, 347.48) per FBG quintile respectively (P < 0.001). CONCLUSIONS: We provide evidence of J-shaped associations between FBG and risk of severe and critical condition in non-diabetes patients with COVID-19, with nadir at 4.74-5.78 mmol/L.


Subject(s)
Blood Glucose/analysis , Coronavirus Infections/blood , Coronavirus Infections/pathology , Fasting/blood , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Adult , Aged , Betacoronavirus/physiology , COVID-19 , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Disease Progression , Female , Humans , Hyperglycemia/blood , Hyperglycemia/complications , Hyperglycemia/diagnosis , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
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