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1.
J Viral Hepat ; 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1769744

ABSTRACT

In 2014, an analysis was conducted to evaluate the hepatitis C virus (HCV) epidemiology and disease burden in Germany. Since then, there have been considerable developments in HCV management like the implementation of direct acting antivirals. The aim of this analysis was to assess the recent data available for Germany, establish an updated 2020 HCV prevalence and cascade of care, and evaluate the impact of what-if scenarios on the future burden of disease using modelling analysis.A dynamic Markov model was used to forecast the HCV disease burden in Germany. Model inputs were retrieved through literature review, unpublished sources, and expert-input. Next, three "what-if" scenarios were developed to evaluate the status quo, COVID-19 pandemic, and steps needed to achieve the WHO targets for elimination. At the beginning of 2020, there were 189,000 (95% UI: 76,700 - 295,000) viremic infections in Germany, a decline of more than 85,000 viremic infections since 2012. Annual treatment starts went down since 2015. Compared to 2019, the COVID-19 pandemic resulted in a further 11% decline in 2020. If this continues for two years, it could result in 110 excess HCC cases and 200 excess liver related deaths by 2030. To achieve the WHO targets, 81,200 people need to be diagnosed, with 118,600 initiated on treatment by 2030. This could also avert 1,020 deaths and 720 HCC cases between 2021 and 2030.Germany has made strides toward HCV elimination, but more efforts are needed to achieve the WHO targets by 2030.

2.
Diabetes Care ; 45(3): 692-700, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1638713

ABSTRACT

OBJECTIVE: Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS: We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS: Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS: Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.


Subject(s)
COVID-19 , Diabetes Mellitus , Hyperglycemia , Biomarkers , Diabetes Mellitus/epidemiology , Female , Hospital Mortality , Hospitalization , Humans , Inflammation , Male , Middle Aged , SARS-CoV-2
3.
J Am Heart Assoc ; 10(24): e023535, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1566424

ABSTRACT

Background Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) is thought to affect COVID-19 through modulating levels of angiotensin-converting enzyme 2, the cell entry receptor for SARS-CoV2. We sought to assess the association between ACEi/ARB, biomarkers of inflammation, and outcomes in patients hospitalized for COVID-19. Methods and Results We leveraged the ISIC (International Study of Inflammation in COVID-19), identified patients admitted for symptomatic COVID-19 between February 1, 2020 and June 1, 2021 for COVID-19, and examined the association between in-hospital ACEi/ARB use and all-cause death, need for ventilation, and need for dialysis. We estimated the causal effect of ACEi/ARB on the composite outcomes using marginal structural models accounting for serial blood pressure and serum creatinine measures. Of 2044 patients in ISIC, 1686 patients met inclusion criteria, of whom 398 (23.6%) patients who were previously on ACEi/ARB received at least 1 dose during their hospitalization for COVID-19. There were 215 deaths, 407 patients requiring mechanical ventilation, and 124 patients who required dialysis during their hospitalization. Prior ACEi/ARB use was associated with lower levels of soluble urokinase plasminogen activator receptor and C-reactive protein. In multivariable analysis, in-hospital ACEi/ARB use was associated with a lower risk of the composite outcome of in-hospital death, mechanical ventilation, or dialysis (adjusted hazard ratio 0.49, 95% CI [0.36-0.65]). Conclusions In patients hospitalized for COVID-19, ACEi/ARB use was associated with lower levels of inflammation and lower risk of in-hospital outcomes. Clinical trials will define the role of ACEi/ARB in the treatment of COVID-19. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 , Hospital Mortality , COVID-19/drug therapy , COVID-19/mortality , Hospitalization , Humans , Inflammation , RNA, Viral , Retrospective Studies
4.
BMJ Open Gastroenterol ; 8(1)2021 10.
Article in English | MEDLINE | ID: covidwho-1476451

ABSTRACT

We present a case of a male patient in his mid-30s with COVID-19-induced lung failure requiring extracorporeal membrane oxygenation, who needed an emergency oesophagogastroduodenoscopy due to major upper gastrointestinal bleeding. Endoscopy exposed severe ulcerative duodenitis with diffuse mucosal bleeding. While CT angiography did not show any signs of ischaemia, histopathology revealed duodenitis with substantial inflammatory cell infiltrates consisting of neutrophils and CD3+ T lymphocytes with equal CD4+/CD8+ distribution. Since the composition of cell infiltrates coincides with changes in inflammatory patterns of the respiratory mucosa from patients with COVID-19 and in COVID-19-associated enterocolitis, and systemic dexamethasone treatment became standard of care in ventilated intensive care unit patients with COVID-19 infection, we initiated an individualised therapeutic attempt to treat the duodenitis with topical enteral budesonide. Follow-up oesophagogastroduodenoscopies within 4 weeks of enteral budesonide administration revealed a full clinical and histological healing of the duodenal mucosa with marked reduction of neutrophilic and lymphocytic infiltrates.To our knowledge, the current report is the first description of enteral budesonide treatment of duodenitis in a patient with COVID-19 infection and warrants further investigation, whether budesonide might constitute a novel therapeutic strategy for the management of COVID-19-related intestinal mucosal damage.


Subject(s)
COVID-19 , Duodenitis , Budesonide/adverse effects , Duodenitis/chemically induced , Gastrointestinal Hemorrhage/chemically induced , Humans , Male , SARS-CoV-2
5.
J Clin Med ; 10(17)2021 Aug 30.
Article in English | MEDLINE | ID: covidwho-1390662

ABSTRACT

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is the result of a hyper-inflammatory reaction to the severe acute respiratory syndrome coronavirus 2. The biomarkers of inflammation have been used to risk-stratify patients with COVID-19. Osteopontin (OPN) is an integrin-binding glyco-phosphoprotein involved in the modulation of leukocyte activation; its levels are associated with worse outcomes in patients with sepsis. Whether OPN levels predict outcomes in COVID-19 is unknown. METHODS: We measured OPN levels in serum of 341 hospitalized COVID-19 patients collected within 48 h from admission. We characterized the determinants of OPN levels and examined their association with in-hospital outcomes; notably death, need for mechanical ventilation, and need for renal replacement therapy (RRT) and as a composite outcome. The risk discrimination ability of OPN was compared with other inflammatory biomarkers. RESULTS: Patients with COVID-19 (mean age 60, 61.9% male, 27.0% blacks) had significantly higher levels of serum OPN compared to healthy volunteers (96.63 vs. 16.56 ng/mL, p < 0.001). Overall, 104 patients required mechanical ventilation, 35 needed dialysis, and 53 died during their hospitalization. In multivariable analyses, OPN levels ≥140.66 ng/mL (third tertile) were associated with a 3.5 × (95%CI 1.44-8.27) increase in the odds of death, and 4.9 × (95%CI 2.48-9.80) increase in the odds of requiring mechanical ventilation. There was no association between OPN and need for RRT. Finally, OPN levels in the upper tertile turned out as an independent prognostic factor of event-free survival with respect to the composite endpoint. CONCLUSION: Higher OPN levels are associated with increased odds of death and mechanical ventilation in patients with COVID-19, however, their utility in triage is questionable.

6.
J Clin Invest ; 131(9)2021 05 03.
Article in English | MEDLINE | ID: covidwho-1223642

ABSTRACT

Cholangiopathies caused by biliary epithelial cell (BEC) injury represent a leading cause of liver failure. No effective pharmacologic therapies exist, and the underlying mechanisms remain obscure. We aimed to explore the mechanisms of bile duct repair after targeted BEC injury. Injection of intermedilysin into BEC-specific human CD59 (hCD59) transgenic mice induced acute and specific BEC death, representing a model to study the early signals that drive bile duct repair. Acute BEC injury induced cholestasis followed by CCR2+ monocyte recruitment and BEC proliferation. Using microdissection and next-generation RNA-Seq, we identified 5 genes, including Mapk8ip2, Cdkn1a, Itgb6, Rgs4, and Ccl2, that were most upregulated in proliferating BECs after acute injury. Immunohistochemical analyses confirmed robust upregulation of integrin αvß6 (ITGß6) expression in this BEC injury model, after bile duct ligation, and in patients with chronic cholangiopathies. Deletion of the Itgb6 gene attenuated BEC proliferation after acute bile duct injury. Macrophage depletion or Ccr2 deficiency impaired ITGß6 expression and BEC proliferation. In vitro experiments revealed that bile acid-activated monocytes promoted BEC proliferation through ITGß6. Our data suggest that BEC injury induces cholestasis, monocyte recruitment, and induction of ITGß6, which work together to promote BEC proliferation and therefore represent potential therapeutic targets for cholangiopathies.


Subject(s)
Antigens, Neoplasm/biosynthesis , Bile Acids and Salts/metabolism , Biliary Tract/metabolism , Cell Proliferation , Epithelial Cells/metabolism , Integrins/biosynthesis , Macrophage Activation , Macrophages/metabolism , Up-Regulation , Animals , Antigens, Neoplasm/genetics , Bile Acids and Salts/genetics , Female , Humans , Integrins/genetics , Male , Mice , Mice, Transgenic , RNA-Seq
9.
JHEP Rep ; 3(3): 100260, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1096063

ABSTRACT

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

10.
EMBO Mol Med ; 13(4): e13191, 2021 04 09.
Article in English | MEDLINE | ID: covidwho-1068062

ABSTRACT

SARS-CoV-2, the agent that causes COVID-19, invades epithelial cells, including those of the respiratory and gastrointestinal mucosa, using angiotensin-converting enzyme-2 (ACE2) as a receptor. Subsequent inflammation can promote rapid virus clearance, but severe cases of COVID-19 are characterized by an inefficient immune response that fails to clear the infection. Using primary epithelial organoids from human colon, we explored how the central antiviral mediator IFN-γ, which is elevated in COVID-19, affects epithelial cell differentiation, ACE2 expression, and susceptibility to infection with SARS-CoV-2. In mouse and human colon, ACE2 is mainly expressed by surface enterocytes. Inducing enterocyte differentiation in organoid culture resulted in increased ACE2 production. IFN-γ treatment promoted differentiation into mature KRT20+ enterocytes expressing high levels of ACE2, increased susceptibility to SARS-CoV-2 infection, and resulted in enhanced virus production in infected cells. Similarly, infection-induced epithelial interferon signaling promoted enterocyte maturation and enhanced ACE2 expression. We here reveal a mechanism by which IFN-γ-driven inflammatory responses induce a vulnerable epithelial state with robust replication of SARS-CoV-2, which may have an impact on disease outcome and virus transmission.


Subject(s)
COVID-19/etiology , Interferon-gamma/immunology , Models, Immunological , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/immunology , COVID-19/pathology , Cell Differentiation/immunology , Colon/immunology , Colon/pathology , Colon/virology , Disease Susceptibility , Enterocytes/metabolism , Enterocytes/pathology , Enterocytes/virology , Gene Expression , Host Microbial Interactions/immunology , Humans , Interferon-gamma/administration & dosage , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Mice , Organoids/immunology , Organoids/pathology , Organoids/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Virus Replication/immunology
11.
J Am Soc Nephrol ; 31(11): 2725-2735, 2020 11.
Article in English | MEDLINE | ID: covidwho-789004

ABSTRACT

BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.


Subject(s)
Acute Kidney Injury/etiology , Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Receptors, Urokinase Plasminogen Activator/blood , Acute Kidney Injury/blood , Acute Kidney Injury/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , Female , Humans , Incidence , Male , Middle Aged , Pandemics , SARS-CoV-2
12.
(J. Hepatol., 4, 73).
Non-conventional in English | WHO COVID, ELSEVIER | ID: covidwho-765069
14.
Infection ; 48(4): 619-626, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-597401

ABSTRACT

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. METHODS: Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, and pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. RESULTS: Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional, and health-related quality-of-life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care, (ii) facilitate comprehensive data collection in medical care facilities with varying resources, and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. CONCLUSION: We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00021688).


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Registries , Berlin/epidemiology , Betacoronavirus , Biological Specimen Banks , COVID-19 , Coronavirus Infections/epidemiology , Disease Management , Humans , Observational Studies as Topic , Pandemics , Phenotype , Pneumonia, Viral/epidemiology , Prospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Time Factors , Treatment Outcome , World Health Organization
15.
Am J Transplant ; 20(7): 1826-1836, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-108935

ABSTRACT

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a drastic impact on national health care systems. Given the overwhelming demand on facility capacity, the impact on all health care sectors has to be addressed. Solid organ transplantation represents a field with a high demand on staff, intensive care units, and follow-up facilities. The great therapeutic value of organ transplantation has to be weighed against mandatory constraints of health care capacities. In addition, the management of immunosuppressed recipients has to be reassessed during the ongoing coronavirus disease 2019 (COVID-19) pandemic. In addressing these crucial questions, transplant physicians are facing a total lack of scientific evidence. Therefore, the aim of this study was to offer an approach of consensus-based guidance, derived from individual information of 22 transplant societies. Key recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found for temporarily suspending nonurgent transplant procedures and living donation programs. Systematic polymerase chain reaction-based testing of donors and recipients was broadly recommended. Additionally, more specific aspects (eg, screening of surgical explant teams and restricted use of marginal donor organs) were included in our analysis. This study offers a novel approach to informed guidance for health care management when a priori no scientific evidence is available.


Subject(s)
Clinical Laboratory Techniques , Coronavirus Infections/prevention & control , Organ Transplantation/standards , Organ Transplantation/trends , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Betacoronavirus , COVID-19 , COVID-19 Testing , Consensus , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Critical Care , Evidence-Based Medicine , Health Policy , Humans , Immunocompromised Host , Internationality , Living Donors , Organ Transplantation/methods , Personal Protective Equipment , Pneumonia, Viral/epidemiology , Polymerase Chain Reaction , Radiography, Thoracic , Resource Allocation , SARS-CoV-2 , Societies, Medical , Tissue Donors , Tomography, X-Ray Computed , Transplant Recipients
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