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1.
Liver Int ; 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1784710

ABSTRACT

BACKGROUND&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) between 03/2020-07/2021 at the Vienna General Hospital were included. Patients were stratified for age: 18-39 vs. 40-69 vs. ≥70years (y). Aspartate aminotransferase (AST), alanine-aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) were recorded. RESULTS: 900 patients (18-39y: 32.2%, 40-69y: 39.7%, ≥70y: 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<0.001). 1.7% of patients without pre-existing liver disease died of liver-related causes, i.e. consequences of hepatic dysfunction or acute liver failure. Importantly, COVID-19-associated liver injury (16.0%, p<0.001), abnormal liver chemistries and liver-related mortality (6.5%, p<0.001) were most frequent among 40-69y old patients. Elevated AST and BIL after first positive SARS-CoV-2 PCR independently predicted mortality in the overall cohort and in 40-69y old patients. CONCLUSIONS: Almost half of COVID-19 patients exhibit abnormal hepatocellular and cholestasis-related liver chemistries with 40-69y 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 for mortality, especially in patients aged 40-69y.

2.
Ann Intern Med ; 174(1): 139-140, 2021 01.
Article in English | MEDLINE | ID: covidwho-1554303
3.
J Pers Med ; 11(12)2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1542639

ABSTRACT

(1) Background: Cirrhotic patients have an increased risk for severe COVID-19. We investigated the renin-angiotensin-aldosterone system (RAS), parameters of endothelial dysfunction, inflammation, and coagulation/fibrinolysis in cirrhotic patients and in COVID-19 patients. (2) Methods: 127 prospectively characterized cirrhotic patients (CIRR), along with nine patients with mild COVID-19 (mild-COVID), 11 patients with COVID-19 acute respiratory distress syndrome (ARDS; ARDS-COVID), and 10 healthy subjects (HS) were included in the study. Portal hypertension (PH) in cirrhotic patients was characterized by hepatic venous pressure gradient (HVPG). (3) Results: With increased liver disease severity (Child-Pugh stage A vs. B vs. C) and compared to HS, CIRR patients exhibited higher RAS activity (angiotensin-converting enzyme (ACE), renin, aldosterone), endothelial dysfunction (von Willebrand-factor (VWF) antigen), inflammation (C-reactive protein (CRP), interleukin-6 (IL-6)), and a disturbed coagulation/fibrinolysis profile (prothrombin fragment F1,2, D-dimer, plasminogen activity, antiplasmin activity). Increased RAS activity (renin), endothelial dysfunction (vWF), coagulation parameters (D-dimer, prothrombin fragment F1,2) and inflammation (CRP, IL-6) were significantly altered in COVID patients and followed similar trends from mild-COVID to ARDS-COVID. In CIRR patients, ACE activity was linked to IL-6 (ρ = 0.26; p = 0.003), independently correlated with VWF antigen (aB: 0.10; p = 0.001), and was inversely associated with prothrombin fragment F1,2 (aB: -0.03; p = 0.023) and antiplasmin activity (aB: -0.58; p = 0.006), after adjusting for liver disease severity. (4) Conclusions: The considerable upregulation of the RAS in Child-Pugh B/C cirrhosis is linked to systemic inflammation, endothelial dysfunction, and abnormal coagulation profile. The cirrhosis-associated abnormalities of ACE, IL-6, VWF antigen, and antiplasmin parallel those observed in severe COVID-19.

4.
PLoS One ; 16(8): e0256544, 2021.
Article in English | MEDLINE | ID: covidwho-1374151

ABSTRACT

BACKGROUND: Patients with hepatocellular carcinoma (HCC) represent a vulnerable population potentially negatively affected by COVID-19-associated reallocation of healthcare resources. Here, we report the impact of COVID-19 on the management of HCC patients in a large tertiary care hospital. METHODS: We retrospectively analyzed clinical data of HCC patients who presented at the Vienna General Hospital, between 01/DEC/2019 and 30/JUN/2020. We compared patient care before (period 1) and after (period 2) implementation of COVID-19-associated healthcare restrictions on 16/MAR/2020. RESULTS: Of 126 patients, majority was male (n = 104, 83%) with a mean age of 66±11 years. Half of patients (n = 57, 45%) had impaired liver function (Child-Pugh stage B/C) and 91 (72%) had intermediate-advanced stage HCC (BCLC B-D). New treatment, was initiated in 68 (54%) patients. Number of new HCC diagnoses did not differ between the two periods (n = 14 vs. 14). While personal visits were reduced, an increase in teleconsultation was observed (period 2). Number of patients with visit delays (n = 31 (30%) vs. n = 10 (10%); p = 0.001) and imaging delays (n = 25 (25%) vs. n = 7 (7%); p = 0.001) was higher in period 2. Accordingly, a reduced number of patients was discussed in interdisciplinary tumor boards (lowest number in April (n = 24), compared to a median number of 57 patients during period 1). Median number of elective/non-elective admissions was not different between the periods. One patient contracted COVID-19 with lethal outcome. CONCLUSIONS: Changes in patient care included reduced personal contacts but increased telephone visits, and delays in diagnostic procedures. The effects on long-term outcome need to be determined.


Subject(s)
COVID-19/epidemiology , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , COVID-19/virology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Delayed Diagnosis , Female , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Pandemics , Patients/psychology , Retrospective Studies , SARS-CoV-2/isolation & purification , Survival Rate , Telemedicine , Tertiary Care Centers
5.
Endosc Int Open ; 9(9): E1315-E1320, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1368969

ABSTRACT

Background and study aims On February 25, 2020, the first patient was diagnosed with COVID-19 in Austria. On March 16, 2020, the Austrian government imposed restrictions and subsequently the Austrian Medical Association recommended minimizing screening examinations in compliance with government restrictions. The aims of this study were to evaluate the impact of this recommendation on the number of colonoscopies performed weekly and detection of non-advanced adenomas, advanced adenomas (AA) and colorectal cancer (CRC) and to calculate how many undetected adenomas could have developed into CRC. Methods We analyzed the number of colonoscopies and pathological findings within a quality assured national colorectal cancer screening program before the COVID-19 pandemic (March 1, t 2019 to September 1, 2019, Period 1) and compared those rates to months during which access to colonoscopy was limited (March 1, 2020 and September 1, 2020, Period 2) with a Wilcoxon-rank-test and a chi-square test. Results A total of 29,199 screening colonoscopies were performed during Period 1 and 24,010 during Period 2. The mean rate of colonoscopies per week during Period 1 was significantly higher than during Period 2 (808,35 [SD = 163,75] versus 594,50 [SD = 282,24], P  = 0.005). A total of 4,498 non-advanced adenomas were detected during Period 1 versus 3,562 during Period 2 ( P  < 0.001). In total 1,317 AAs and 140 CRCs were detected during Period 1 versus 919 AAs and 106 CRCs during Period 2. These rates did not differ significantly ( P  = 0.2 and P  = 0.9). Conclusions During the COVID-19 crisis, the number of colonoscopies performed per week was significantly lower compared to the year before, but there was no difference in the detection of CRCs and AAs.

6.
Pathologe ; 42(2): 155-163, 2021 Mar.
Article in German | MEDLINE | ID: covidwho-1235728

ABSTRACT

BACKGROUND: COVID-19 is considered a systemic disease. A severe course with fatal outcome is possible and unpredictable. OBJECTIVES: Which organ systems are predominantly involved? Which diseases are predisposed for a fatal course? Which organ changes are found with lethal outcome? MATERIALS AND METHODS: Data from published autopsy studies (28 cases by our group) with respect to organ changes and possible cause of death. RESULTS: The most severe alterations are found in the lungs by diffuse alveolar damage as a symptom of an acute respiratory distress syndrome (ARDS), in part with fibrosis. Thrombosis of small- to mid-sized pulmonary arteries is associated with hemorrhagic lung infarction. Frequent complications are bacterial pneumonias and less frequently fungal pneumonias by aspergillus. Pulmonary thromboembolism is found in 20-30% of lethal courses, also in the absence of deep venous thrombosis. Intestinal involvement of COVID-19 can be associated with intestinal ischemia, caused by shock or local thrombosis. In most cases, the kidneys display acute tubular injury reflecting acute renal failure, depletion of lymphocytes in the lymph nodes and spleen, and hyperplastic adrenal glands. The liver frequently reveals steatosis, liver cell necrosis, portal inflammation, and proliferation of Kupffer cells. Important preexisting diseases in autopsy studies are arterial hypertension with hypertensive and ischemic cardiomyopathy and diabetes mellitus but large population-based studies reveal increased risk of mortality only for diabetes mellitus not for arterial hypertension. CONCLUSIONS: Alterations of the pulmonary circulation with pulmonary arterial thrombosis, infarction, and bacterial pneumonia are important and often lethal complications of COVID-19-associated ARDS. Findings from autopsy studies have influenced therapy and prophylaxis.


Subject(s)
COVID-19 , Thrombosis , Autopsy , Humans , Lung , SARS-CoV-2
7.
Hepatol Commun ; 5(10): 1660-1675, 2021 10.
Article in English | MEDLINE | ID: covidwho-1233191

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic necessitated down-scaling of in-hospital care to prohibit the spread of severe acute respiratory syndrome-coronavirus-2. We (1) assessed patient perceptions on quality of care by telesurvey (cohort 1) and written questionnaire (cohort 2), and (2) analyzed trends in elective and nonelective admissions before (December 2019 to February 2020) and during (March to May 2020) the COVID-19 pandemic in Austria. A total of 279 outpatients were recruited into cohort 1 and 138 patients into cohort 2. All admissions from December 2019 to May 2020 to the Division of Gastroenterology/Hepatology at the Vienna General Hospital were analyzed. A total of 32.6% (n = 91 of 279) of cohort 1 and 72.5% (n = 95 of 131) of cohort 2 had telemedical contact, whereas 59.5% (n = 166 of 279) and 68.2% (n = 90 of 132) had face-to-face visits. A total of 24.1% (n = 32 of 133) needed acute medical help during health care restrictions; however, 57.3% (n = 51 of 89) reported that contacting their physician during COVID-19 was difficult or impossible. Patient-reported satisfaction with treatment decreased significantly during restrictions in cohort 1 (visual analog scale [VAS] 0-10: 9.0 ± 1.6 to 8.6 ± 2.2; P < 0.001) and insignificantly in cohort 2 (VAS 0-10: 8.9 ± 1.6 to 8.7 ± 2.1; P = 0.182). Despite fewer hospital admissions during COVID-19, the proportion of nonelective admissions (+6.3%) and intensive care unit admissions (+6.7%) increased. Patients with cirrhosis with nonelective admissions during COVID-19 had significantly higher Model for End-Stage Liver Disease (MELD) (25.5 [14.2] vs. 17.0 [interquartile range: 8.8]; P = 0.003) and ΔMELD (difference from last MELD: 3.9 ± 6.3 vs. 8.7 ± 6.4; P = 0.008), required immediate intensive care more frequently (26.7% vs. 5.6%; P = 0.034), and had significantly increased 30-day liver-related mortality (30.0% vs. 8.3%; P = 0.028). Conclusion: The COVID-19 pandemic's effects on quality of liver care is evident from decreased patient satisfaction, hospitalization of sicker patients with advanced chronic liver disease, and increased liver-related mortality. Strategies for improved telemedical liver care and preemptive treatment of cirrhosis-related complications are needed to counteract the COVID-19-associated restrictions of in-hospital care.


Subject(s)
COVID-19 , Gastroenterology , Liver Diseases/therapy , Patient Satisfaction , Quality of Health Care , Telemedicine , Aged , Austria , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/therapy , Chronic Disease , Delivery of Health Care , End Stage Liver Disease , Female , Hospitalization , Humans , Intensive Care Units , Liver Diseases/mortality , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Liver Transplantation , Male , Middle Aged , SARS-CoV-2 , Severity of Illness Index , Surveys and Questionnaires
8.
Pathologe ; 42(2): 155-163, 2021 Mar.
Article in German | MEDLINE | ID: covidwho-1082488

ABSTRACT

BACKGROUND: COVID-19 is considered a systemic disease. A severe course with fatal outcome is possible and unpredictable. OBJECTIVES: Which organ systems are predominantly involved? Which diseases are predisposed for a fatal course? Which organ changes are found with lethal outcome? MATERIALS AND METHODS: Data from published autopsy studies (28 cases by our group) with respect to organ changes and possible cause of death. RESULTS: The most severe alterations are found in the lungs by diffuse alveolar damage as a symptom of an acute respiratory distress syndrome (ARDS), in part with fibrosis. Thrombosis of small- to mid-sized pulmonary arteries is associated with hemorrhagic lung infarction. Frequent complications are bacterial pneumonias and less frequently fungal pneumonias by aspergillus. Pulmonary thromboembolism is found in 20-30% of lethal courses, also in the absence of deep venous thrombosis. Intestinal involvement of COVID-19 can be associated with intestinal ischemia, caused by shock or local thrombosis. In most cases, the kidneys display acute tubular injury reflecting acute renal failure, depletion of lymphocytes in the lymph nodes and spleen, and hyperplastic adrenal glands. The liver frequently reveals steatosis, liver cell necrosis, portal inflammation, and proliferation of Kupffer cells. Important preexisting diseases in autopsy studies are arterial hypertension with hypertensive and ischemic cardiomyopathy and diabetes mellitus but large population-based studies reveal increased risk of mortality only for diabetes mellitus not for arterial hypertension. CONCLUSIONS: Alterations of the pulmonary circulation with pulmonary arterial thrombosis, infarction, and bacterial pneumonia are important and often lethal complications of COVID-19-associated ARDS. Findings from autopsy studies have influenced therapy and prophylaxis.


Subject(s)
COVID-19 , Thrombosis , Autopsy , Humans , Lung , SARS-CoV-2
9.
Pathol Res Pract ; 217: 153305, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-947348

ABSTRACT

Autopsies on COVID-19 have provided deep insights into a novel disease with unpredictable and potentially fatal outcome. A standardized autopsy procedure preferably with an in-situ technique and systematic tissue processing is important. Strict safety measures include personal protective equipment with a standardized protocol for dressing and undressing, usage of FFP-3 masks and minimization of aerosol production. The use of an airborne infection isolation (AIIR) room is preferred. Viral RNA analysis using swabs from throat, both lungs and other organs provides information on cross-organ viral dynamics. To correctly determine the full extent of pathological organ changes an adequate processing procedure is of the utmost importance. Systematic dissection and processing of the lungs revealed pulmonary infarction caused by thrombosis and thromboembolism and bacterial bronchopneumonia as the most frequent cause of death. Fungal pneumonia (aspergillus) was found in one case. The quality of the tissue was sufficient for histopathological and immunohistochemistry analyses in all cases. Viral RNA from throat or lung swabs was detectable post mortem in 89 % of the cases and could also be detected from paraffin-embedded tissue by real-time PCR. Complete COVID-19 autopsies including extensive histopathological studies and viral RNA analysis require approximately three times more human and technical resources and time compared to standard non-COVID autopsies. Autopsies on COVID-19 are feasible, present a manageable risk, while following a strict protocol, and provide novel insights into disease pathogenesis and the clinician with important feedback.


Subject(s)
Autopsy/methods , Autopsy/standards , COVID-19/pathology , Occupational Health/standards , COVID-19/mortality , COVID-19/transmission , Cause of Death , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Personal Protective Equipment , SARS-CoV-2 , Specimen Handling/methods , Specimen Handling/standards
10.
Liver Int ; 41(1): 20-32, 2021 01.
Article in English | MEDLINE | ID: covidwho-944760

ABSTRACT

The recent outbreak of coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a world-wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID-19. Although liver failure does not seem to occur in the absence of pre-existing liver disease, hepatic involvement in COVID-19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID-19 may range from direct infection by SARS-CoV-2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS-CoV-2 hepatic tropism as well as acute and possibly long-term liver injury in COVID-19.


Subject(s)
COVID-19/complications , Liver Diseases/etiology , Liver/virology , SARS-CoV-2 , Viral Tropism , Angiotensin-Converting Enzyme 2/physiology , Cholestasis/etiology , Humans , Non-alcoholic Fatty Liver Disease/etiology
12.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1215

ABSTRACT

Background: COVID-19 caused by the novel SARS-CoV-2 has rapidly become pandemic and has an estimated mortality rate of 3·4% of infected individuals. However, th

13.
Virchows Arch ; 478(2): 343-353, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-725586

ABSTRACT

The persistence of SARS-CoV-2 after death of infected individuals is unclear. The aim of this study was to investigate the presence of SARS-CoV-2 RNA in different organs in correlation with tissue damage and post-mortem viral dynamics in COVID-19 deceased. Twenty-eight patients (17 males, 11 females; age 66-96 years; mean 82.9, median 82.5 years) diagnosed with COVID-19 were studied. Swabs were taken post-mortem during autopsy (N = 19) from the throat, both lungs, intestine, gallbladder, and brain or without autopsy (N = 9) only from the throat. Selective amplification of target nucleic acid from the samples was achieved by using primers for ORF1a/b non-structural region and the structural protein envelope E-gene of the virus. The results of 125 post-mortem and 47 ante-mortem swabs were presented as cycle threshold (Ct) values and categorized as strong, moderate, and weak. Viral RNA was detected more frequently in the lungs and throat than in the intestine. Blood, bile, and the brain were negative. Consecutive throat swabs were positive up to 128 h after death without significant increase of Ct values. All lungs showed diffuse alveolar damage, thrombosis, and infarction and less frequently bronchopneumonia irrespective of Ct values. In 30% the intestine revealed focal ischemic changes. Nucleocapsid protein of SARS-CoV-2 was detected by immunohistochemistry in bronchial and intestinal epithelium, bronchial glands, and pneumocytes. In conclusion, viral RNA is still present several days after death, most frequently in the respiratory tract and associated with severe and fatal organ damage. Potential infectivity cannot be ruled out post-mortem.


Subject(s)
COVID-19/pathology , COVID-19/virology , SARS-CoV-2/physiology , Viral Tropism , Aged , Aged, 80 and over , Autopsy , Female , Humans , Immunohistochemistry , Male , Prospective Studies , RNA, Viral/analysis , SARS-CoV-2/isolation & purification , Severity of Illness Index
15.
Ann Intern Med ; 173(5): 350-361, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-305562

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN: Prospective autopsy study. SETTING: Single pathology department. PARTICIPANTS: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. LIMITATION: The sample was small. CONCLUSION: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory and imaging studies, and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. PRIMARY FUNDING SOURCE: None.


Subject(s)
Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Pulmonary Artery , Thrombosis/mortality , Aged , Aged, 80 and over , Autopsy , Betacoronavirus , COVID-19 , Female , Humans , Male , Pandemics , Prospective Studies , Real-Time Polymerase Chain Reaction , SARS-CoV-2
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