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1.
Medicina (Kaunas) ; 58(7)2022 Jun 23.
Article in English | MEDLINE | ID: covidwho-1911467

ABSTRACT

BACKGROUND: This study aimed to calculate the frequency of elevated liver enzymes in hospitalized patients with coronavirus disease 2019 (COVID-19) infection and to test if liver enzyme biochemistry levels on admission could predict the computed tomography (CT) scan severity score of bilateral interstitial pneumonia. METHODS: This single-center study comprised of 323 patients including their demographic data, laboratory analyses, and radiological findings. All the information was taken from electronic health records, followed by statistical analysis. RESULTS: Out of 323 patients, 115 of them (35.60%) had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) over 40 U/L on admission. AST was the best predictor of CT scan severity score of bilateral interstitial pneumonia (R2 = 0.313, Adjusted R2 = 0.299). CT scan severity score in the peak of the infection could be predicted with the value of AST, neutrophils, platelets, and monocytes count (R2 = 0.535, Adjusted R2 = 0.495). CONCLUSION: AST, neutrophils, platelets, and monocytes count on admission can account for almost half (49.5%) of the variability in CT scan severity score at peak of the disease, predicting the extensiveness of interstitial pneumonia related to COVID-19 infection. Liver enzymes should be closely monitored in order to stratify COVID-19 patients with a higher risk of developing severe forms of the disease and to plan the beforehand step-up treatment.


Subject(s)
COVID-19 , Pneumonia , Alanine Transaminase , Aspartate Aminotransferases , Humans , Retrospective Studies , SARS-CoV-2
2.
Clin Lab ; 68(5)2022 May 01.
Article in English | MEDLINE | ID: covidwho-1835714

ABSTRACT

BACKGROUND: Highly infectious viruses such as SARS-CoV-2, MERS-CoV, and Ebola virus represent a threat to clinical laboratory workers. We aimed to investigate how virus inactivation by heating at 60°C for 1 hour affects routine clinical laboratory indicators. METHODS: Each collected serum sample was separated into two aliquots, and various indicators were measured in first aliquot after inactivation by heating at 60°C for 1 hour and in the second after room-temperature incubation for 1 hour. RESULTS: Serological test results for 36 indicators remained mostly unaffected by heat inactivation, with a mean estimated bias of < 10%. By contrast, the results for alanine transaminase, pseudocholinesterase, creatine kinase, lactate dehydrogenase, cardiac troponin I, and myoglobin were affected by heat inactivation, with the mean esti-mated bias here being > 20%, which was further increased in the case of the results for alkaline phosphatase, lipase, and creatine kinase isoenzyme MB. Immunological serological measurements showed good agreement according to Kappa consistency checks after heat inactivation of serum. The results for alanine transaminase, pseudocholinesterase, creatine kinase, lactate dehydrogenase, cardiac troponin I, and myoglobin were significantly correlated (r > 0.95) after heat inactivation, and after correction by using a regression equation, the results for the indicators still retained a clinical reference value. CONCLUSIONS: Inactivation by heating at 60°C for 1 hour exerts no marked effect on numerous routine biochemical and immunological indicators in serum, but the detection values for certain items are significantly decreased. Our method could serve as reference strategy for routine serological diagnostics in patients with suspected or confirmed infection with highly pathogenic viruses.


Subject(s)
COVID-19 , Virus Inactivation , Alanine Transaminase , Butyrylcholinesterase , Creatine Kinase , Creatine Kinase, MB Form , Heating , Humans , Lactate Dehydrogenases , Myoglobin , SARS-CoV-2 , Troponin I
3.
Int J Mol Sci ; 23(9)2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1809943

ABSTRACT

Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8-3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.


Subject(s)
Antiviral Agents , COVID-19 , Chemical and Drug Induced Liver Injury , Alanine Transaminase , Antiviral Agents/adverse effects , Aspartate Aminotransferases , COVID-19/drug therapy , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Female , Humans , Male , Middle Aged , Publications
4.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1801469

ABSTRACT

Corona virus disease is a global pandemic. One of the key issues has been the very high volume of patients presenting to health centres or hospitals during the outbreak. It clearly overwhelms the human and mechanistic capacities available. Therefore, early and effective predictors of clinical outcomes are required for risk stratification. MATERIAL: This is hospital based retrospective study on patients who were admitted in Covid wards/ICU at IGGMC. Patients were divided into 3 groups- mild-moderate; severe; and critical based on their clinical presentation on admission. Several biomarkers like WBC, platelets, N/L, CRP, LDH, S. ferritin, d-dimer, CPK-MB, Serum creatinine, BUL, SGOT, SGPT, Serum albumin were analysed before and after treatment. OBSERVATION: 110 patients were enrolled in this study, 36 were classified into mild-moderate, 56 into severe and 18 into critical. As all of mild-moderate patients were discharged and majority of critical patients expired, biomarkers were compared between severe patients who were discharged vs severe patients who died. Out of these biomarkers, CRP was significantly decreased during course of treatment in severe patients who were discharged (p = 0.004) in comparison to severe patients who died where CRP was significantly increased (p = 0.001) (p value of difference being 0.00001). There was also significant change in ferritin levels (p = 0.006), while other biomarkers like WBC (p = 0.07), platelets (p = 0.066), N/L (p = 0.3), LDH (p = 0.06), d-dimer (p = 0.1), CPK-MB (p = 0.49), serum creatinine (p = 0.05), urea (p = 0.06), S. albumin (p= 0.3), SGOT (p =0.07), SGPT (p=0.25) did not show promising results. In addition, various treatment protocols were analysed by comparing CRP before and after treatment. Severe patients were divided into 2 groups, who took injection Remdesivir along with antibiotics, LMWH, systemic steroids vs who didn't, and CRP level were compared, but the difference was not significant (p = 0.06). Pre and post treatment CRP was also compared for Tocilizumab, Fevipiravir, Hydroxychloroquine, Doxycyline, but none of them were able to decrease CRP significantly (p > 0.05) in the severe or critical group but these drugs were effective in reducing CRP significantly (p<0.05) when given in mild-moderate group or if the treatment was started early. CONCLUSION: Increment in CRP and ferritin could effectively predict clinical outcome and could be used for risk stratification but no available drug is effective in reducing these biomarkers significantly in severe or critical group.


Subject(s)
COVID-19 , Heparin, Low-Molecular-Weight , Alanine Transaminase , Aspartate Aminotransferases , Biomarkers , Creatinine , Ferritins , Humans , Prognosis , Retrospective Studies
5.
Liver Int ; 42(6): 1297-1307, 2022 06.
Article in English | MEDLINE | ID: covidwho-1784710

ABSTRACT

BACKGROUND AND AIMS: The coronavirus disease of 2019 (COVID-19) causes considerable mortality worldwide. We aimed to investigate the frequency and predictive role of abnormal liver chemistries in different age groups. METHODS: Patients with positive severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test between 03/2020-07/2021 at the Vienna General Hospital were included. Patients were stratified for age: 18-39 vs. 40-69 vs. ≥70 years (y). Aspartate aminotransferase (AST), alanine-aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) were recorded. RESULTS: 900 patients (18-39 years: 32.2%, 40-69 years: 39.7%, ≥70 years: 28.1%) were included. Number of comorbidities, median D-dimer and C-reactive protein increased with age. During COVID-19, AST/ALT and ALP/GGT levels significantly increased. Elevated hepatocellular transaminases (AST/ALT) and cholestasis parameters (ALP/GGT/BIL) were observed in 40.3% (n  = 262/650) and 45.0% (n  = 287/638) of patients respectively. Liver-related mortality was highest among patients with pre-existing decompensated liver disease (28.6%, p < .001). 1.7% of patients without pre-existing liver disease died of liver-related causes, that is consequences of hepatic dysfunction or acute liver failure. Importantly, COVID-19-associated liver injury (16.0%, p < .001), abnormal liver chemistries and liver-related mortality (6.5%, p < .001) were most frequent among 40-69 years old patients. Elevated AST and BIL after the first positive SARS-CoV-2 PCR independently predicted mortality in the overall cohort and in 40-69 years old patients. CONCLUSIONS: Almost half of the COVID-19 patients exhibit abnormal hepatocellular and cholestasis-related liver chemistries with 40-69 years old patients being at particularly high risk for COVID-19-related liver injury and liver-related mortality. Elevated AST and BIL after SARS-CoV-2 infection are independent predictors of mortality, especially in patients aged 40-69 years.


Subject(s)
COVID-19 , Cholestasis , Liver Diseases , Adolescent , Adult , Aged , Alanine Transaminase , Alkaline Phosphatase , Aspartate Aminotransferases , Bilirubin/metabolism , Humans , Liver , Liver Diseases/metabolism , Middle Aged , SARS-CoV-2 , Young Adult , gamma-Glutamyltransferase/metabolism
7.
Clin Gastroenterol Hepatol ; 20(7): 1553-1560.e78, 2022 07.
Article in English | MEDLINE | ID: covidwho-1729615

ABSTRACT

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has witnessed more than 4.5 million deaths as of the time of writing. Whether nonalcoholic fatty liver disease (NAFLD) increases the risk for severe COVID-19 remains unclear. We sought to address this question using 2-sample Mendelian randomization (TSMR) analysis approaches in large cohorts. METHODS: We performed large-scale TSMR analyses to examine whether there is a causal relationship between NAFLD, serum alanine aminotransferase, grade of steatosis, NAFLD Activity Score, or fibrosis stage and severe COVID-19. To maximize the power of this analysis, we performed a genome-wide meta-analysis to identify single nucleotide polymorphisms associated with NAFLD. We also examined the impact of 20 major comorbid factors of NAFLD on severe COVID-19. RESULTS: Univariate analysis of the UK Biobank data demonstrated a significant association between NAFLD and severe COVID-19 (odds ratio [OR], 3.06; P = 1.07 × 10-6). However, this association disappeared after demographic and comorbid factors were adjusted (OR, 1.57; P = .09). TSMR study indicated that NAFLD (OR, 0.97; P = .61), alanine aminotransferase level (OR, 1.03; P = .47), grade of steatosis (OR, 1.08; P = .41), NAFLD Activity Score (OR, 1.02; P = .39), and fibrosis stage (OR, 1.01; P = .87) were not associated with severe COVID-19. Among all NAFLD-related comorbid factors, body mass index (OR, 1.73; P = 7.65 × 10-9), waist circumference (OR, 1.76; P = 2.58 × 10-5), and hip circumference (OR, 1.33; P = 7.26 × 10-3) were the only ones demonstrated a causal impact on severe COVID-19. CONCLUSIONS: There is no evidence supporting that NAFLD is a causal risk factor for severe COVID-19. Previous observational associations between NAFLD and COVID-19 are likely attributed to the correlation between NAFLD and obesity.


Subject(s)
COVID-19 , Non-alcoholic Fatty Liver Disease , Alanine Transaminase , Body Mass Index , COVID-19/complications , Fibrosis , Humans , Mendelian Randomization Analysis , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/genetics
9.
World J Gastroenterol ; 28(5): 570-587, 2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1674889

ABSTRACT

BACKGROUND: Abnormal liver chemistries are common findings in patients with Coronavirus Disease 2019 (COVID-19). However, the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understood. AIM: We aimed to assess the prevalence of elevated liver chemistries in hospitalized patients with COVID-19 and compare the serum liver chemistries to predict the severity and in-hospital mortality. METHODS: This retrospective, observational study included 3380 patients with COVID-19 who were hospitalized in the Johns Hopkins Health System (Baltimore, MD, United States). Demographic data, clinical characteristics, laboratory findings, treatment measures, and outcome data were collected. Cox regression modeling was used to explore variables associated with abnormal liver chemistries on admission with disease severity and prognosis. RESULTS: A total of 2698 (70.4%) had abnormal alanine aminotransferase (ALT) at the time of admission. Other more prevalent abnormal liver chemistries were aspartate aminotransferase (AST) (44.4%), alkaline phosphatase (ALP) (16.1%), and total bilirubin (T-Bil) (5.9%). Factors associated with liver injury were older age, Asian ethnicity, other race, being overweight, and obesity. Higher ALT, AST, T-Bil, and ALP levels were more commonly associated with disease severity. Multivariable adjusted Cox regression analysis revealed that abnormal AST and T-Bil were associated with the highest mortality risk than other liver injury indicators during hospitalization. Abnormal AST, T-Bil, and ALP were associated with a need for vasopressor drugs, whereas higher levels of AST, T-Bil, and a decreased albumin levels were associated with mechanical ventilation. CONCLUSION: Abnormal liver chemistries are common at the time of hospital admission in COVID-19 patients and can be closely related to the patient's severity and prognosis. Elevated liver chemistries, specifically ALT, AST, ALP, and T-Bil levels, can be used to stratify risk and predict the need for advanced therapies in these patients.


Subject(s)
COVID-19 , Liver/chemistry , Alanine Transaminase , Alkaline Phosphatase , Aspartate Aminotransferases , Baltimore , Bilirubin , COVID-19/diagnosis , COVID-19/therapy , Hospitalization , Humans , Retrospective Studies , Severity of Illness Index
10.
J Paediatr Child Health ; 58(5): 802-808, 2022 05.
Article in English | MEDLINE | ID: covidwho-1570906

ABSTRACT

AIM: Although chest computed tomography (CT) score has been well evaluated in adult coronavirus disease (COVID-19), its use in paediatric cases is insufficiently studied. Our aim is to evaluate the relationship of chest CT score with disease severity and laboratory parameters. METHODS: Seventy-six paediatric patients with confirmed COVID-19 and chest CT evaluation on admission have been included in this study. Chest CT score was calculated for each of the five lobes considering the extent of anatomical involvement, as follows: 0: 0%; 1: <5%; 2: 5%-25%; 3: 26%-50%; 4: 51%-75% and 5: >75%. The resulting total CT score was the sum of each individual lobar score; the range was between 0 and 25. RESULTS: Total chest CT score was found to be positively correlated with alanine aminotransferase and d-dimer, and negatively correlated with lymphocyte count. In receiver operating characteristic analysis, total chest CT score had area under the curve 0.99 (95% confidence interval, 0.98-1.00) at cut-off 2 with 95% sensitivity and 96% specificity for the severe disease. Furthermore, in-depth analysis of lobar CT scores showed a correlation between left upper lobe with lymphocyte count, left lower lobe with d-dimer, right middle and lower lobes with alanine aminotransferase and right upper lobe with leukocyte count. CONCLUSIONS: There is a significant relationship between chest CT score and COVID-19 severity and laboratory findings in children. This suggests that chest CT scores can be used to assess the severity of the disease and can play an important role in paediatric clinical practice.


Subject(s)
COVID-19 , SARS-CoV-2 , Alanine Transaminase , COVID-19/diagnostic imaging , Child , Humans , Lung , Retrospective Studies , Severity of Illness Index , Tomography, X-Ray Computed/methods
11.
Lab Med ; 52(5): 493-498, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1526169

ABSTRACT

OBJECTIVE: The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. METHODS: We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. RESULTS: Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3-2.95 vs median, 0.82 nmol/L; interquartile range, 0.57-1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001). CONCLUSION: We found that MR-proADM could represent a prognostic biomarker of COVID-19.


Subject(s)
Adrenomedullin/blood , COVID-19/diagnosis , Hypertension/diagnosis , Lung Diseases/diagnosis , Protein Precursors/blood , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/mortality , COVID-19/virology , Comorbidity , Female , Humans , Hypertension/blood , Hypertension/mortality , Hypertension/virology , Interleukin-6/blood , Lung Diseases/blood , Lung Diseases/mortality , Lung Diseases/virology , Male , Middle Aged , Patient Selection , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis , Triage/methods
12.
Eur Rev Med Pharmacol Sci ; 25(21): 6813-6824, 2021 11.
Article in English | MEDLINE | ID: covidwho-1524868

ABSTRACT

OBJECTIVE: The aim of the study was to appraise the capacity of serum aminotransferases to discriminate between hepatic and other extra-pulmonary COVID-19-related manifestations and, potentially, to serve as predictors of poor clinical outcomes. MATERIALS AND METHODS: Ninety-eight studies were identified (79% from China), including 43,554 patients (57% males), 9,983 (62% males) with poor outcomes and 33,571 (50% males) with favorable outcomes. After splitting studies depending on whether serum alanine aminotransferase (ALT) concentrations were statistically different between patients with poor vs. favorable outcomes, the 35 'hepatic involvement' articles (p<0.05) included 28,510 patients (51% males), 5,279 (66% males) and 23,231 subjects (48% males) with poor and favorable outcomes, respectively. The 63 'extra-hepatic involvement' studies (p>0.05) included 15,044 patients (54% males), 4,704 (60% males) with poor outcomes and 10,340 (51% males) with favorable outcomes. RESULTS: The meta-analysis shows that serum aspartate aminotransferase (AST) concentrations were significantly higher in patients with poor outcomes than those with favorable outcomes (WMD 12.5 UI/L, 95% CI 10.9 to 14.1 p<0.001). Similarly, AST concentrations were significantly higher in the 'hepatic involvement' studies (WMD 16.3 UI/L, 95% CI 13.4 to 19.2 p<0.001) and in the 'extra-hepatic involvement' studies (WMD 10.3 UI/L, 95% CI 8.6 to 12.0 p<0.001). CONCLUSIONS: The different association of serum AST concentrations with some clinical, demographic, and biochemical factors in the two clusters suggests that in COVID-19 patients, serum AST elevation is not necessarily linked to real liver damage.


Subject(s)
Alanine Transaminase/blood , Aspartate Aminotransferases/blood , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Databases, Factual , Humans , SARS-CoV-2/isolation & purification , Treatment Outcome
13.
Dis Markers ; 2021: 3440714, 2021.
Article in English | MEDLINE | ID: covidwho-1484098

ABSTRACT

BACKGROUND: It has been observed that COVID-19 may cause myocardial damage, but there are few detailed reports on myocardial enzyme abnormalities. METHODS: In this retrospective study, we analyzed data from 157 consecutive laboratory-confirmed and hospitalized COVID-19 patients from Wuhan. We collected information on demographic and clinical characteristics, laboratory findings, and clinical outcomes. Logistic regression analysis was used to explore the risk factors associated with the severity of COVID-19. The association between myocardial enzyme abnormalities and the mortality was also investigated. RESULTS: The mortality in abnormal myocardial enzyme group was obviously higher than the normal group (P < 0.001). The majority of patients (n = 72, 97.3%) with normal cardiac enzyme group were of the common novel coronavirus pneumonia (NCP) type, whereas half of the patients with cardiac enzyme abnormalities (n = 40, 48.2%) developed critical and severe NCP type. The multivariable logistic regression analysis indicated that COVID-19 patients with increasing age (P = 0.035), higher levels of CRP (P = 0.038), and TNI (P = 0.036) were associated with increased death than other patients. CONCLUSIONS: Myocardial enzyme abnormality and myocardial injury were associated with the severity and fatal outcomes of COVID-19. Clinicians should pay attention to the markers of myocardial injury in COVID-19 patients, especially those with older age, comorbidities, and inflammation.


Subject(s)
COVID-19/enzymology , COVID-19/mortality , Enzymes/blood , Myocardium/enzymology , Adult , Alanine Transaminase/blood , COVID-19/blood , Creatine Kinase, MB Form/blood , Female , Humans , L-Lactate Dehydrogenase/blood , Logistic Models , Male , Middle Aged , Retrospective Studies , Troponin I/blood
14.
BMC Infect Dis ; 21(1): 818, 2021 Aug 16.
Article in English | MEDLINE | ID: covidwho-1477280

ABSTRACT

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.


Subject(s)
COVID-19/complications , Liver/virology , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers/blood , COVID-19/blood , COVID-19/epidemiology , Female , Humans , Liver/pathology , Liver Function Tests/methods , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
15.
Clin Transl Sci ; 15(2): 524-534, 2022 02.
Article in English | MEDLINE | ID: covidwho-1476158

ABSTRACT

The safety of novel therapeutics and vaccines are typically assessed in early phase clinical trials involving "healthy volunteers." Abnormalities in such individuals can be difficult to interpret and may indicate previously unrecognized medical conditions. The frequency of incidental findings (IFs) in healthy volunteers who attend for clinical trial screening is unclear. To assess this, we retrospectively analyzed data for 1838 "healthy volunteers" screened for enrolment in a UK multicenter, phase I/II severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) vaccine trial. Participants were predominantly White (89.7%, 1640/1828) with a median age of 34 years (interquartile range [IQR] = 27-44). There were 27.7% of participants (510/1838) who had at least one IF detected. The likelihood of identifying evidence of a potential, new blood-borne virus infection was low (1 in 238 participants) compared with identification of an elevated alanine transaminase (ALT; 1 in 17 participants). A large proportion of participants described social habits that could impact negatively on their health; 21% consumed alcohol in excess, 10% were current smokers, 11% described recreational drug use, and only 48% had body weight in the ideal range. Our data demonstrate that screening prior to enrollment in early phase clinical trials identifies a range of IFs, which should inform discussion during the consent process. Greater clarity is needed to ensure an appropriate balance is struck between early identification of medical problems and avoidance of exclusion of volunteers due to spurious or physiological abnormalities. Debate should inform the role of the trial physician in highlighting and advising about unhealthy social habits.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Incidental Findings , SARS-CoV-2/immunology , Adult , Alanine Transaminase/blood , Body Mass Index , Female , Healthy Volunteers , Humans , Male , Retrospective Studies
16.
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
17.
Front Immunol ; 12: 715072, 2021.
Article in English | MEDLINE | ID: covidwho-1430697

ABSTRACT

Background: Prediction of the severity of COVID-19 at its onset is important for providing adequate and timely management to reduce mortality. Objective: To study the prognostic value of damage parameters and cytokines as predictors of severity of COVID-19 using an extensive immunologic profiling and unbiased artificial intelligence methods. Methods: Sixty hospitalized COVID-19 patients (30 moderate and 30 severe) and 17 healthy controls were included in the study. The damage indicators high mobility group box 1 (HMGB1), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), extensive biochemical analyses, a panel of 47 cytokines and chemokines were analyzed at weeks 1, 2 and 7 along with clinical complaints and CT scans of the lungs. Unbiased artificial intelligence (AI) methods (logistic regression and Support Vector Machine and Random Forest algorithms) were applied to investigate the contribution of each parameter to prediction of the severity of the disease. Results: On admission, the severely ill patients had significantly higher levels of LDH, IL-6, monokine induced by gamma interferon (MIG), D-dimer, fibrinogen, glucose than the patients with moderate disease. The levels of macrophage derived cytokine (MDC) were lower in severely ill patients. Based on artificial intelligence analysis, eight parameters (creatinine, glucose, monocyte number, fibrinogen, MDC, MIG, C-reactive protein (CRP) and IL-6 have been identified that could predict with an accuracy of 83-87% whether the patient will develop severe disease. Conclusion: This study identifies the prognostic factors and provides a methodology for making prediction for COVID-19 patients based on widely accepted biomarkers that can be measured in most conventional clinical laboratories worldwide.


Subject(s)
COVID-19/pathology , Diagnosis, Computer-Assisted/methods , Severity of Illness Index , Support Vector Machine , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers/analysis , Cytokines/blood , Female , HMGB1 Protein/blood , Humans , L-Lactate Dehydrogenase/blood , Macrophages/immunology , Male , Middle Aged , Monocytes/immunology , Prognosis , Prospective Studies , SARS-CoV-2
18.
Iran J Med Sci ; 46(4): 237-255, 2021 07.
Article in English | MEDLINE | ID: covidwho-1395708

ABSTRACT

Background: The outbreak of the coronavirus disease-2019 (COVID-19) has become a global public health challenge. Assessing the effect of COVID-19 on liver injury is of great importance. A systematic review and meta-analysis were conducted to establish the characteristics of liver function tests in COVID-19 patients. Methods: A systematic search of publications from December 2019 up to April 2020 in Web of Science, Scopus, and Medline (via PubMed) databases was performed. Both cross-sectional and case series studies reporting an association between liver injury and COVID-19 infection were included. The data were analyzed using the STATA software (version 11.0) and the random-effects model for I2>50% was used to pool the results. Results: In this meta-analysis, 42 articles comprising a total of 6,557 COVID-19 patients were studied. The prevalence of increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was 30% and 21% in non-severe patients and 38% and 48% in severe patients, respectively. Patients with severe COVID-19 infection were 4.22, 4.96, and 4.13 times more likely to have elevated AST, ALT, and lactate dehydrogenase (LDH) levels, respectively. Conclusion: Elevation in liver function tests was higher in patients with severe than non-severe COVID-19 infection. Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients. The inclusion of other studies from outside China could confirm the pattern of elevation in liver function tests in COVID-19 patients across the globe. Preprint of this article is available on medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.20.20108357v1.


Subject(s)
COVID-19/complications , Liver Diseases/virology , Liver Function Tests , Alanine Transaminase , Aspartate Aminotransferases , Humans , L-Lactate Dehydrogenase , Liver/enzymology , Liver Diseases/epidemiology
20.
Clin Chim Acta ; 522: 88-95, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1356157

ABSTRACT

BACKGROUND: Aspartate aminotransferase (AST) is often increased in COVID-19 and, in some studies, AST abnormalities were associated with mortality risk. METHODS: 2054 hospitalized COVID-19 patients were studied. To identify sources of AST release, correlations between AST peak values and other biomarkers of tissue damage, i.e., alanine aminotransferase (ALT) for hepatocellular damage, creatine kinase (CK) for muscle damage, lactate dehydrogenase for multiorgan involvement, alkaline phosphatase and γ-glutamyltransferase for cholestatic injury, and C-reactive protein (CRP) for systemic inflammation, were performed and coefficients of determination estimated. The role of AST to predict death and intensive care unit admission during hospitalization was also evaluated. All measurements were performed using standardized assays. RESULTS: AST was increased in 69% of patients. Increases could be fully explained by summing the effects of hepatocellular injury [AST dependence from ALT, 66.8% [95% confidence interval (CI): 64.5-69.1)] and muscle damage [AST dependence from CK, 42.6% (CI: 39.3-45.8)]. We were unable to demonstrate an independent association of AST increases with worse outcomes. CONCLUSION: The mechanisms for abnormal AST in COVID-19 are likely multifactorial and a status related to tissue suffering could play a significant role. The clinical significance of AST elevations remains unclear.


Subject(s)
COVID-19 , Liver Diseases , Alanine Transaminase , Aspartate Aminotransferases , Humans , SARS-CoV-2
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