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1.
Bratisl Lek Listy ; 122(10): 732-738, 2021.
Article in English | MEDLINE | ID: covidwho-1441311

ABSTRACT

BACKGROUND: The use of acetaminophen (APAP) is increasing recently, especially with COVID-19 outbreaks. APAP is safe at therapeutic levels, however, an overdose can cause severe liver injury. This study aims to explore possible mechanisms involved in APAP­induced hepatotoxicity and compare different hepatoprotective agents, namely vitamin E, hydrogen sulfide (H2S) and necrostatin-1 (NEC-1). METHODS: Adult male albino rats were divided into groups: Control group, APAP­induced hepatotoxicity group, Vitamin E­treated group, H2S­treated group and NEC-1­treated group. Serum levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-33 (IL-33), tumor necrosis factor alpha (TNF-α), reduced glutathione (GSH) and lipid profile were measured. Histopathological examinations of liver tissue with H(et)E stain and immunohistochemistry for activated caspase-3 were also done. RESULTS: APAP­treated group showed elevated liver transaminases, hyperlipidemia, and deficient liver anti-oxidative response together with disturbed hepatic architecture and increased immune-expression of activated caspase-3 in hepatic tissue. Pretreatment with vitamin E, H2S or NEC-1 reversed the affected parameters. Vitamin E and H2S showed greater improvement when compared to NEC-1. CONCLUSION: Vitamin E, H2S and NEC-1 showed protective effects against APAP-induced hepatotoxicity, thus they may be used as an adjuvant therapy when APAP is indicated for long periods as is the case in COVID-19 patients (Tab. 2, Fig. 2, Ref. 45). Text in PDF www.elis.sk Keywords: acetaminophen, hepatotoxicity, apoptosis, necrostatin-1, vitamin E, H2S.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , Hydrogen Sulfide , Acetaminophen/toxicity , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Humans , Hydrogen Sulfide/metabolism , Imidazoles , Indoles , Liver/metabolism , Male , Oxidative Stress , Rats , SARS-CoV-2 , Vitamin E/pharmacology
2.
Life Sci ; 284: 119881, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1347741

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an infectious disease that has spread worldwide. Current treatments are limited in both availability and efficacy, such that improving our understanding of the factors that facilitate infection is urgently needed to more effectively treat infected individuals and to curb the pandemic. We and others have previously demonstrated the significance of interactions between the SARS-CoV-2 spike protein, integrin α5ß1, and human ACE2 to facilitate viral entry into host cells in vitro. We previously found that inhibition of integrin α5ß1 by the clinically validated small peptide ATN-161 inhibits these spike protein interactions and cell infection in vitro. In continuation with our previous findings, here we have further evaluated the therapeutic potential of ATN-161 on SARS-CoV-2 infection in k18-hACE2 transgenic (SARS-CoV-2 susceptible) mice in vivo. We discovered that treatment with single or repeated intravenous doses of ATN-161 (1 mg/kg) within 48 h after intranasal inoculation with SARS-CoV-2 lead to a reduction of lung viral load, viral immunofluorescence, and improved lung histology in a majority of mice 72 h post-infection. Furthermore, ATN-161 reduced SARS-CoV-2-induced increased expression of lung integrin α5 and αv (an α5-related integrin that has also been implicated in SARS-CoV-2 interactions) as well as the C-X-C motif chemokine ligand 10 (Cxcl10), further supporting the potential involvement of these integrins, and the anti-inflammatory potential of ATN-161, respectively, in SARS-CoV-2 infection. To the best of our knowledge, this is the first study demonstrating the potential therapeutic efficacy of targeting integrin α5ß1 in SARS-CoV-2 infection in vivo and supports the development of ATN-161 as a novel SARS-CoV-2 therapy.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/prevention & control , Oligopeptides/therapeutic use , SARS-CoV-2/physiology , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , COVID-19/virology , Genome, Viral , Humans , Integrins/metabolism , Liver/enzymology , Liver/pathology , Lung/pathology , Lung/virology , Male , Mice, Inbred C57BL , Mice, Transgenic , Oligopeptides/pharmacology , SARS-CoV-2/genetics , Staining and Labeling , Viral Load/genetics
3.
PLoS One ; 16(4): e0249346, 2021.
Article in English | MEDLINE | ID: covidwho-1190165

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). OBJECTIVE: To describe the clinical characteristics of patients with ARDS-COVID-19. MATERIALS AND METHODS: This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP)], thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH). RESULTS: The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. CONCLUSION: COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Respiratory Distress Syndrome/virology , Adult , Aged , Alanine Transaminase/blood , Alanine Transaminase/metabolism , Aspartate Aminotransferases/blood , Aspartate Aminotransferases/metabolism , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/virology , Creatinine/blood , Creatinine/metabolism , Egypt/epidemiology , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , L-Lactate Dehydrogenase/blood , L-Lactate Dehydrogenase/metabolism , Leukocyte Count , Lymphocyte Count , Lymphopenia/blood , Male , Middle Aged , Platelet Count , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/epidemiology , SARS-CoV-2/isolation & purification , Severity of Illness Index
4.
Eur J Gastroenterol Hepatol ; 33(5): 691-694, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1159992

ABSTRACT

BACKGROUND: Infection due to severe acute respiratory syndrome coronavirus 2 is typically associated with a respiratory syndrome, but gastrointestinal symptoms have been described in early reports from China. However, data from European centres are scarce. OBJECTIVES: We aimed to characterise the gastrointestinal manifestations of patients with coronavirus disease 2019 (COVID-19) and their disease course. METHODS: Patients admitted at our centre between March and April 2020 with diagnosis of COVID-19 were included. Asymptomatic patients or those without symptom information were excluded. Clinical features, laboratory data and disease severity (mechanical ventilation, intensive care admission or death) were analysed. RESULTS: Two-hundred one patients were included (median age 71 years; 56.2% male). Digestive symptoms were reported by 60 (29.9%) patients during the disease course, being part of the disease presentation in 34 (16.9%). The most frequent were diarrhoea in 36 patients (17.9%). Patients with gastrointestinal symptoms were younger (P = 0.032), had higher haemoglobin levels (P = 0.002) and lower C-reactive protein (P = 0.045) and potassium levels (P = 0.004). Patients with digestive symptoms had less severe disease (28.3 vs. 44.0%; P = 0.038). Regarding liver damage, aspartate aminotransferase (AST) was elevated in 65.2% of patients and alanine aminotransferase (ALT) in 62.7%, but these patients did not present a more severe disease (elevated AST P = 0.062; elevated ALT P = 0.276). CONCLUSION: A significant portion of COVID-19 patients have digestive symptoms, mostly at presentation. This should be taken into account in order to keep a high level of suspicion to reach an early diagnosis and setup infection control measures to control the transmission rate. This subgroup of patients appears to have a less severe disease course.


Subject(s)
COVID-19/physiopathology , Diarrhea/physiopathology , Vomiting/physiopathology , Abdominal Pain/epidemiology , Abdominal Pain/metabolism , Abdominal Pain/physiopathology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Ageusia/epidemiology , Ageusia/metabolism , Ageusia/physiopathology , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , C-Reactive Protein/metabolism , COVID-19/metabolism , Diarrhea/epidemiology , Diarrhea/metabolism , Female , Hemoglobins/metabolism , Humans , Male , Middle Aged , Nausea/epidemiology , Nausea/metabolism , Nausea/physiopathology , Portugal/epidemiology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Vomiting/epidemiology , Vomiting/metabolism , Young Adult
5.
Clin Infect Dis ; 71(16): 2079-2088, 2020 11 19.
Article in English | MEDLINE | ID: covidwho-1153156

ABSTRACT

BACKGROUND: This study aimed to develop mortality-prediction models for patients with coronavirus disease-2019 (COVID-19). METHODS: The training cohort included consecutive COVID-19 patients at the First People's Hospital of Jiangxia District in Wuhan, China, from 7 January 2020 to 11 February 2020. We selected baseline data through the stepwise Akaike information criterion and ensemble XGBoost (extreme gradient boosting) model to build mortality-prediction models. We then validated these models by randomly collected COVID-19 patients in Union Hospital, Wuhan, from 1 January 2020 to 20 February 2020. RESULTS: A total of 296 COVID-19 patients were enrolled in the training cohort; 19 died during hospitalization and 277 discharged from the hospital. The clinical model developed using age, history of hypertension, and coronary heart disease showed area under the curve (AUC), 0.88 (95% confidence interval [CI], .80-.95); threshold, -2.6551; sensitivity, 92.31%; specificity, 77.44%; and negative predictive value (NPV), 99.34%. The laboratory model developed using age, high-sensitivity C-reactive protein, peripheral capillary oxygen saturation, neutrophil and lymphocyte count, d-dimer, aspartate aminotransferase, and glomerular filtration rate had a significantly stronger discriminatory power than the clinical model (P = .0157), with AUC, 0.98 (95% CI, .92-.99); threshold, -2.998; sensitivity, 100.00%; specificity, 92.82%; and NPV, 100.00%. In the subsequent validation cohort (N = 44), the AUC (95% CI) was 0.83 (.68-.93) and 0.88 (.75-.96) for the clinical model and laboratory model, respectively. CONCLUSIONS: We developed 2 predictive models for the in-hospital mortality of patients with COVID-19 in Wuhan that were validated in patients from another center.


Subject(s)
COVID-19/mortality , COVID-19/virology , Coronavirus/pathogenicity , Adult , Aspartate Aminotransferases/metabolism , COVID-19/epidemiology , China/epidemiology , Cohort Studies , Coronavirus/enzymology , Female , Glomerular Filtration Rate/physiology , Hospital Mortality , Humans , Male , Middle Aged
7.
Gerontology ; 67(3): 255-266, 2021.
Article in English | MEDLINE | ID: covidwho-1013078

ABSTRACT

OBJECTIVE: We aim to investigate the clinical characteristics and risk factors for the severe cases of coronavirus disease 2019 (COVID-19) in comparison with the non-severe patients. METHODS: We searched PubMed, EMBASE, Web of Science, and CNKI to collect all relevant studies published before July 26, 2020, and a total of 30 papers were included in this meta-analysis. RESULTS: In the severe COVID-19 patients, 60% (95% CI = 56-64%) were male, 25% (95% CI = 21-29%) were over 65 years old, 34% (95% CI = 24-44%) were obese, and 55% (95% CI = 41-70%) had comorbidities. The most prevalent comorbidities were hypertension (34%, 95% CI = 25-44%), diabetes (20%, 95% CI = 15-25%), and cardiovascular disease (CVD; 12%, 95% CI = 9-16%). The most common blood test abnormalities were elevated C-reactive protein (CRP; 87%, 82-92%), decreased lymphocyte count (68%, 58-77%), and increased lactate dehydrogenase (69%, 95% CI = 57-81%). In addition, abnormal laboratory findings revealing organ dysfunctions were frequently observed in the severe cases, including decrease in albumin (43%, 95% CI = 24-63%) and increase in aspartate aminotransferase (47%, 95% CI = 38-56%), alanine aminotransferase (28%, 95% CI = 16-39%), troponin I/troponin T (TnI/TnT; 29%, 95% CI = 13-45%), and serum Cr (SCr; 10%, 95% CI = 5-15%). CONCLUSION: The male, elderly and obese patients and those with any comorbidities, especially with hypertension, diabetes, and CVD, were more likely to develop into severe cases. But the association between hypertension, diabetes, CVD, and severity of COVID-19 was declined by the increase of age. A significant elevation in cardiac TnI/TnT, the hepatic enzymes, and SCr and the reduction in lymphocytes with elevated CRPs are important markers for the severity. Specific attention should be given to the elderly male and obese patients and those with indications of severe immune injury in combination with bacterial infection and indication of multi-organ dysfunction or damages.


Subject(s)
COVID-19/epidemiology , COVID-19/metabolism , Age Distribution , Age Factors , Aged , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , C-Reactive Protein/metabolism , COVID-19/physiopathology , Cardiovascular Diseases/epidemiology , Comorbidity , Creatinine/metabolism , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , L-Lactate Dehydrogenase/metabolism , Lymphopenia , Male , Middle Aged , Obesity/epidemiology , Risk Factors , SARS-CoV-2 , Sex Distribution , Troponin I/metabolism , Troponin T/metabolism
8.
Respiration ; 99(9): 739-747, 2020.
Article in English | MEDLINE | ID: covidwho-934161

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global emerging infectious disease. OBJECTIVES: To analyze the initial clinical characteristics of COVID-19 suspected and confirmed patients on admission in order to find out which kinds may be more likely to get positive nucleic acid testing results, and to explore the risk factors associated with all-cause death. METHODS: Medical records from 309 highly suspected cases with pneumonia were collected from February 13, 2020, to March 14, 2020, in a COVID-19-designated hospital of Wuhan. The majority of the clinical data were collected on the first day of hospital admission. RESULTS: Of 309 patients with median age 64 years (interquartile ranges [IQR], 53-72 years), 111 patients (35.9%) were confirmed by nucleic acid testing (median age 64 years, IQR: 56-71 years; 48 males). Of those 111 patients, 13 (11.7%) patients died. In multivariate analysis, factors associated with positive testing included fatigue (odds ratios [OR] = 3.14; 95% confidence interval [CI]: 1.88-5.24, p < 0.001), cough (OR = 0.55; 95% CI: 0.32-0.95, p = 0.032), no less than 1 comorbidity (OR = 1.77; 95% CI: 1.06-2.98, p = 0.030), and severe pneumonia (OR = 2.67; 95% CI: 1.20-5.97, p = 0.016). Furthermore, age, dyspnea, noneffective antibiotic treatment, white blood cell, lymphocyte, platelets, and organ dysfunction (e.g., higher lactate dehydrogenase) were significantly associated with all-cause in-hospital death in patients with COVID-19. CONCLUSION: Patients with severe forms of this disease were more likely to get positive results. Age and organ dysfunction were associated with a greater risk of death.


Subject(s)
COVID-19/epidemiology , Cough/physiopathology , Fatigue/physiopathology , Hospital Mortality , Pneumonia/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Alanine Transaminase/metabolism , Anti-Bacterial Agents/therapeutic use , Aspartate Aminotransferases/metabolism , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19/metabolism , COVID-19/physiopathology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Cause of Death , Child , Child, Preschool , China/epidemiology , Cohort Studies , Comorbidity , Creatine Kinase/metabolism , Female , Fever/physiopathology , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Immunoglobulin G , Immunoglobulin M , Infant , Infant, Newborn , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , Multivariate Analysis , Pneumonia/drug therapy , Pneumonia/microbiology , Pneumonia/physiopathology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Serum Albumin/metabolism , Severity of Illness Index , Treatment Failure , Young Adult
9.
PLoS One ; 15(11): e0241663, 2020.
Article in English | MEDLINE | ID: covidwho-910303

ABSTRACT

BACKGROUND/AIM: The coronavirus disease 2019 (COVID-19) had become a big threat worldwide. Liver injury is not uncommon in patients with COVID-19, and clarifying its characteristics is needed. This study aimed to identify factors associated with liver injury and to develop a new classification of predictive severity in patients with COVID-19. METHODS: Confirmed patients with COVID-19 (n = 60) were recruited retrospectively from Musashino Red Cross Hospital. The factors of liver injury especially on the elevation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were analyzed. Grading was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: During a median hospitalization follow-up of 15 (4-41) days, 51 (85.0%) patients had COVID-19 pneumonia. In clinical courses, oxygenation was needed for 25 (41.6%) patients and intubation was needed for 9 (15.0%) patients. A total of 27 (45.0%) patients had gastrointestinal symptoms (GS), such as appetite loss, diarrhea, and nausea. A logistic regression analysis revealed that C-reactive protein (CRP) at baseline, oxygenation, intubation, and GS were significant factors of liver injury. Based on these results, patients were classified into three groups: group 1, no oxygenation pneumonia; group 2, pneumonia with oxygenation or GS; and group 3, intubation. We classified 25 (41.7%), 26 (43.3%), and 9 (15.0%) patients into mild, moderate, and severe groups, respectively. The peak of AST and ALT levels was significantly stratified with this criteria (mild [median AST, 28 IU/L; median ALT, 33 IU/L], moderate [median AST, 48 IU/L; median ALT, 47.5 IU/L], and severe [median AST, 109 IU/L; median ALT, 106 IU/L]; P<0.001 and P = 0.0114, respectively). CONCLUSION: COVID-19-related liver injury was significantly stratified based on GS and severity of pneumonia.


Subject(s)
Coronavirus Infections/pathology , Digestive System Diseases/pathology , Digestive System Diseases/virology , Liver Diseases/pathology , Liver Diseases/virology , Pneumonia, Viral/pathology , Pneumonia/pathology , Pneumonia/virology , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , C-Reactive Protein/metabolism , COVID-19 , Digestive System Diseases/metabolism , Female , Follow-Up Studies , Humans , Liver/metabolism , Liver/pathology , Liver/virology , Liver Diseases/metabolism , Male , Middle Aged , Pandemics , Pneumonia/metabolism , Retrospective Studies , Severity of Illness Index
10.
Cardiol Rev ; 29(1): 39-42, 2021.
Article in English | MEDLINE | ID: covidwho-900593

ABSTRACT

Patients older than 65 years hospitalized with COVID-19 have higher rates of intensive care unit admission and death when compared with younger patients. Cardiovascular conditions associated with COVID-19 include myocardial injury, acute myocarditis, cardiac arrhythmias, cardiomyopathies, cardiogenic shock, thromboembolic disease, and cardiac arrest. Few studies have described the clinical course of those at the upper extreme of age. We characterize the clinical course and outcomes of 73 patients with 80 years of age or older hospitalized at an academic center between March 15 and May 13, 2020. These patients had multiple comorbidities and often presented with atypical clinical findings such as altered sensorium, generalized weakness and falls. Cardiovascular manifestations observed at the time of presentation included new arrhythmia in 7/73 (10%), stroke/intracranial hemorrhage in 5/73 (7%), and elevated troponin in 27/58 (47%). During hospitalization, 38% of all patients required intensive care, 13% developed a need for renal replacement therapy, and 32% required vasopressor support. All-cause mortality was 47% and was highest in patients who were ever in intensive care (71%), required mechanical ventilation (83%), or vasopressors (91%), or developed a need for renal replacement therapy (100%). Patients older than 80 years old with COVID-19 have multiple unique risk factors which can be associated with increased cardiovascular involvement and death.


Subject(s)
Acute Kidney Injury/therapy , COVID-19/therapy , Hospital Mortality , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Vasoconstrictor Agents/therapeutic use , Academic Medical Centers , Accidental Falls , Acute Kidney Injury/etiology , Aged, 80 and over , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Aspartate Aminotransferases/metabolism , C-Reactive Protein/metabolism , COVID-19/complications , COVID-19/metabolism , COVID-19/physiopathology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Cause of Death , Consciousness Disorders/physiopathology , Dyspnea/physiopathology , Female , Ferritins/metabolism , Fever/physiopathology , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Hypoxia/physiopathology , Hypoxia/therapy , Independent Living , Intensive Care Units/statistics & numerical data , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/physiopathology , Leukocyte Count , Liver Diseases/etiology , Liver Diseases/metabolism , Lymphocyte Count , Male , Muscle Weakness/physiopathology , Natriuretic Peptide, Brain/metabolism , Nursing Homes , Oxygen Inhalation Therapy , Procalcitonin/metabolism , Stroke/etiology , Stroke/physiopathology , Troponin I/metabolism
11.
Ann Hepatol ; 19(6): 614-621, 2020.
Article in English | MEDLINE | ID: covidwho-753947

ABSTRACT

INTRODUCTION: COVID-19 caused by the SARS-CoV-2 continues to spread rapidly across the world. In our study, we aim to investigate the relationship between the liver enzymes on admission (AST, ALT, ALP, GGT) and severity of COVID-19. We evaluated course of disease, hospital stay, liver damage and mortality. MATERIALS AND METHODS: Our study included 614 patients who were hospitalized with the diagnosis of COVID-19 between 03.16.20 and 05.12.20. Patients with liver disease, hematological and solid organ malignancy with liver metastases were excluded, resulting in 554 patients who met our inclusion criteria. We retrospectively evaluated liver transaminase levels, AST/ALT ratio, cholestatic enzyme levels and R ratio during hospital admission and these were compared in terms of morbidity, mortality and clinical course. RESULTS: Mean age of 554 subjects were 66.21±15.45 years, 328 (59.2%) were men. The mean values of liver enzymes on admission were AST (36.2±33.6U/L), ALT (34.01±49.34U/L), ALP (78.8±46.86U/L), GGT (46.25±60.05U/L). Mortality rate and need for intensive care unit were statistically significant in subjects that had high ALT-AST levels during their admission to the hospital (p=0.001). According to the ROC analysis AST/ALT ratio was a good marker of mortality risk (AUC=0.713: p=0.001) and expected probability of intensive care unit admission (AUC=0.636: p=0.001). R ratio, which was used to evaluate prognosis, showed a poor prognosis rate of 26.5% in the cholestatic injury group, 36.1% in the mixed pattern group and 30% in the hepato-cellular injury group (p 0.001). CONCLUSIONS: ALT-AST elevation and AST/ALT ratio >1 was associated with more severe course and increased mortality in COVID-19.


Subject(s)
Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , Betacoronavirus , Coronavirus Infections/enzymology , Coronavirus Infections/mortality , Liver Diseases/virology , Pneumonia, Viral/enzymology , Pneumonia, Viral/mortality , Adult , Aged , COVID-19 , Coronavirus Infections/complications , Female , Hospitalization , Humans , Liver Diseases/diagnosis , Liver Diseases/mortality , Liver Function Tests , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Prognosis , Retrospective Studies , SARS-CoV-2 , Sensitivity and Specificity , Survival Rate , Turkey
12.
Diabetes Metab J ; 44(4): 602-613, 2020 08.
Article in English | MEDLINE | ID: covidwho-721570

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. METHODS: We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. RESULTS: Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. CONCLUSION: DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.


Subject(s)
Coronavirus Infections/mortality , Diabetes Mellitus/epidemiology , Pneumonia, Viral/mortality , Adult , Aged , Aged, 80 and over , Alanine Transaminase/metabolism , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Aspartate Aminotransferases/metabolism , Betacoronavirus , C-Reactive Protein/metabolism , COVID-19 , Case-Control Studies , Comorbidity , Coronavirus Infections/metabolism , Coronavirus Infections/physiopathology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Female , Humans , Length of Stay/statistics & numerical data , Logistic Models , Lymphocytosis , Male , Middle Aged , Multivariate Analysis , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/physiopathology , Prognosis , Propensity Score , Proportional Hazards Models , Quarantine/statistics & numerical data , Republic of Korea/epidemiology , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Thrombocytopenia
13.
Diabetes Res Clin Pract ; 167: 108351, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-664109

ABSTRACT

AIMS: Coronavirus disease (COVID-19), also referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is instigated by a novel coronavirus. The disease was initially reported in Wuhan, China, in December 2019. Diabetes is a risk factor associated with adverse outcomes. Herein, our objective was to investigate the characteristics of laboratory findings of type 2 diabetes mellitus (T2DM) patients infected with SARS-CoV-2. METHODS: This was a retrospective study and included 80 T2DM patients of Jinling Hospital from 2010 to 2020, as well as 76 COVID-19 patients without T2DM and 55 COVID-19 patients with T2DM who were treated at Huoshen hill Hospital from February 11 to March 18, 2020. We then compared the differences in laboratory test results between the three groups. RESULTS: The levels of lymphocytes, uric acid (UA), and globulin in the T2DM group were significantly higher. In contrast, C-reactive protein (CRP), creatinine, and lactic dehydrogenase (LDH)levels were lower than those in the COVID-19 (p < 0.05) and COVID-19 + T2DM groups (p < 0.05). No considerable difference was observed regarding the levels of alanine aminotransferase (ALT), white blood cell (WBC), aspartate aminotransferase (AST), globulin, and blood urea nitrogen (BUN) in the three groups (p > 0.05). CONCLUSION: T2DM patients infected with SARS-CoV-2 showed decreased levels of body mass index (BMI), lymphocytes, UA, and albumin, and increased CRP levels. The decreased BMI, UA, and albumin levels may be associated with oxidative stress response and nutritional consumption. The decreased lymphocyte counts and increased CRP levels may be related to the infection.


Subject(s)
Coronavirus Infections/metabolism , Diabetes Mellitus, Type 2/metabolism , Pneumonia, Viral/metabolism , Aged , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , Betacoronavirus , Blood Urea Nitrogen , C-Reactive Protein/metabolism , COVID-19 , Case-Control Studies , Comorbidity , Coronavirus Infections/complications , Creatinine/metabolism , Diabetes Mellitus, Type 2/complications , Female , Globulins/metabolism , Humans , L-Lactate Dehydrogenase/metabolism , Lymphocyte Count , Lymphocytes , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Retrospective Studies , Risk Factors , SARS-CoV-2 , Serum Albumin/metabolism , Uric Acid/metabolism
14.
Hosp Pediatr ; 10(10): 902-905, 2020 10.
Article in English | MEDLINE | ID: covidwho-637116

ABSTRACT

Coronavirus disease (COVID-19) has affected children differently from adults worldwide. Data on the clinical presentation of the infection in children are limited. We present a detailed account of pediatric inpatients infected with severe acute respiratory syndrome coronavirus 2 virus at our institution during widespread local transmission, aiming to understand disease presentation and outcomes. A retrospective chart review was performed of children, ages 0 to 18 years, with a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 on nasopharyngeal specimens admitted to our hospital over a 4-week period. We present clinical data from 22 patients and highlight the variability of the presentation. In our study, most children presented without respiratory illness or symptoms suggestive of COVID-19; many were identified only because of universal testing. Because children may have variable signs and symptoms of COVID-19 infection, targeted testing may miss some cases.


Subject(s)
Coronavirus Infections/physiopathology , Cough/physiopathology , Dyspnea/physiopathology , Fatigue/physiopathology , Fever/physiopathology , Pneumonia, Viral/physiopathology , Seizures/physiopathology , Adolescent , Age Distribution , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , Betacoronavirus , C-Reactive Protein/metabolism , COVID-19 , COVID-19 Testing , Child , Child, Preschool , Chronic Disease , Clinical Laboratory Techniques , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/metabolism , Coronavirus Infections/therapy , Female , Heart Diseases/epidemiology , Hospitalization , Hospitals, Pediatric , Humans , Infant , Infant, Newborn , Lung Diseases/epidemiology , Lymphopenia/epidemiology , Male , Mass Screening , Neoplasms/epidemiology , New York City/epidemiology , Noninvasive Ventilation , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/metabolism , Pneumonia, Viral/therapy , Procalcitonin/metabolism , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Sex Distribution , United States
15.
BJOG ; 127(11): 1374-1380, 2020 10.
Article in English | MEDLINE | ID: covidwho-627054

ABSTRACT

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.


Subject(s)
Coronavirus Infections/physiopathology , HELLP Syndrome/physiopathology , Placenta Growth Factor/metabolism , Pneumonia, Viral/physiopathology , Pre-Eclampsia/physiopathology , Pregnancy Complications, Infectious/physiopathology , Uterine Artery/diagnostic imaging , Vascular Endothelial Growth Factor Receptor-1/metabolism , Adult , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , Betacoronavirus , Blood Pressure , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/metabolism , Female , HELLP Syndrome/etiology , HELLP Syndrome/metabolism , Humans , L-Lactate Dehydrogenase/metabolism , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/metabolism , Pre-Eclampsia/etiology , Pre-Eclampsia/metabolism , Pregnancy , Pregnancy Complications, Infectious/metabolism , Proteinuria/etiology , Proteinuria/physiopathology , Pulsatile Flow , SARS-CoV-2 , Severity of Illness Index , Tertiary Care Centers , Thrombocytopenia/etiology , Thrombocytopenia/physiopathology
16.
Eur J Gastroenterol Hepatol ; 32(9): 1244-1250, 2020 09.
Article in English | MEDLINE | ID: covidwho-607768

ABSTRACT

Coronoviraus disease 2019 (COVID-19) has infected over two million people worldwide and the number keeps growing every day. While the pulmonary complications of COVID-19 are obvious, the effect of the virus on the other organs and the chronicity of the organ dysfunction remain unknown. The virus causes a debilitating infection with multiorgan injury and has a high mortality rate estimated to be around 3.70%. Several hypotheses are formulated to explain the liver dysfunction in COVID-19 patients which include collateral damage from cytokine storm, drug-induced liver injury, viral-induced hepatitis and hypoxia-induced damage. Through this case series, we would like to highlight that liver enzyme abnormalities are often seen in COVID-19 patients and would like to highlight that physicians need to serially monitor biochemical testing until the liver enzymes return to baseline. Physicians also need to be vigilant of liver enzyme abnormalities in these patients, especially before starting new medications.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/enzymology , Liver Diseases/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/enzymology , Adult , Aged , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Aspartate Aminotransferases/metabolism , COVID-19 , Female , Humans , Male , Pandemics , SARS-CoV-2
17.
Travel Med Infect Dis ; 36: 101782, 2020.
Article in English | MEDLINE | ID: covidwho-595825

ABSTRACT

INTRODUCTION: There are currently no satisfactory methods for predicting the outcome of Coronavirus Disease-2019 (COVID-19). The aim of this study is to establish a model for predicting the prognosis of the disease. METHODS: The laboratory results were collected from 54 deceased COVID-19 patients on admission and before death. Another 54 recovered COVID-19 patients were enrolled as control cases. RESULTS: Many laboratory indicators, such as neutrophils, AST, γ-GT, ALP, LDH, NT-proBNP, Hs-cTnT, PT, APTT, D-dimer, IL-2R, IL-6, IL-8, IL-10, TNF-α, CRP, ferritin and procalcitonin, were all significantly increased in deceased patients compared with recovered patients on admission. In contrast, other indicators such as lymphocytes, platelets, total protein and albumin were significantly decreased in deceased patients on admission. Some indicators such as neutrophils and procalcitonin, others such as lymphocytes and platelets, continuously increased or decreased from admission to death in deceased patients respectively. Using these indicators alone had moderate performance in differentiating between recovered and deceased COVID-19 patients. A model based on combination of four indicators (P = 1/[1 + e-(-2.658+0.587×neutrophils - 2.087×lymphocytes - 0.01×platelets+0.004×IL-2R)]) showed good performance in predicting the death of COVID-19 patients. When cutoff value of 0.572 was used, the sensitivity and specificity of the prediction model were 90.74% and 94.44%, respectively. CONCLUSIONS: Using the current indicators alone is of modest value in differentiating between recovered and deceased COVID-19 patients. A prediction model based on combination of neutrophils, lymphocytes, platelets and IL-2R shows good performance in predicting the outcome of COVID-19.


Subject(s)
Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Aged , Aged, 80 and over , Alkaline Phosphatase/metabolism , Aspartate Aminotransferases/metabolism , Betacoronavirus , C-Reactive Protein/metabolism , COVID-19 , Case-Control Studies , Coronavirus Infections/blood , Coronavirus Infections/metabolism , Female , Ferritins/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Interleukin-10/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , L-Lactate Dehydrogenase/metabolism , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Models, Theoretical , Natriuretic Peptide, Brain/metabolism , Neutrophils , Pandemics , Partial Thromboplastin Time , Peptide Fragments/metabolism , Pneumonia, Viral/blood , Pneumonia, Viral/metabolism , Procalcitonin/metabolism , Prognosis , Prothrombin Time , ROC Curve , Receptors, Interleukin-2/metabolism , SARS-CoV-2 , Troponin T/metabolism , Tumor Necrosis Factor-alpha/metabolism , gamma-Glutamyltransferase/metabolism
18.
JAMA Netw Open ; 3(6): e2010895, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-505563

ABSTRACT

Importance: The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. Objective: To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. Design, Setting, and Participants: This single-center case series included 157 pediatric patients admitted to Wuhan Children's Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. Exposures: Documented SARS-CoV-2 infection. Main Outcomes and Measures: Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. Results: Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/µL [1680/µL-3510/µL] vs 3120/µL [2040/µL-4170/µL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, -0.3579; AST: r, -0.5280; CK-MB activity: r, -0.4786; LDH: r, -0.4984; and neutrophil to lymphocyte ratio, ALT: r, -0.1893; AST: r, -0.3912; CK-MB activity: r, -0.3428; LDH: r, -0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). Conclusions and Relevance: In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.


Subject(s)
Coronavirus Infections/immunology , Cytokines/immunology , Neutrophils/immunology , Pneumonia, Viral/immunology , Age Distribution , Alanine Transaminase/metabolism , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Aspartate Aminotransferases/metabolism , B-Lymphocytes/immunology , C-Reactive Protein/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19 , Child , Child, Preschool , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/metabolism , Coronavirus Infections/therapy , Creatine Kinase, MB Form/metabolism , Critical Illness , Female , Hospitals, Pediatric , Humans , Infant , Interferon-gamma/immunology , Interleukin-10/immunology , Interleukin-2/immunology , Interleukin-4/immunology , Interleukin-6/immunology , Killer Cells, Natural/immunology , L-Lactate Dehydrogenase/metabolism , Leukocyte Count , Lymphocyte Count , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/metabolism , Pneumonia, Viral/therapy , Severity of Illness Index , Sex Distribution , Tumor Necrosis Factor-alpha/immunology
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