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1.
Open Forum Infect Dis ; 9(4): ofac063, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1740950

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused sudden, severe strain to healthcare systems. Better outpatient management is required to save lives, manage resources effectively, and prepare for future pandemics. Methods: The Coronataxi digital early warning (CDEW) system deployed in Rhein-Neckar County and Heidelberg, Germany is an outpatient care system consisting of remote digital monitoring via a mobile application, a medical doctor dashboard, and medical care delivery to COVID-19 patients in home quarantine when indicated. Patients reported their symptoms, temperature, breathing rate, oxygen saturation, and pulse via the app. This single-center cohort study compared outcomes of the population with and without using the CDEW system. The primary outcome was mortality; the secondary outcomes were hospitalization, duration of hospitalization, intensive care therapy, and mechanical ventilation. Results: Mortality rate was 3- to 4-fold lower and hospitalization rate was higher in the CDEW cohort (459 patients) compared with the cohort without CDEW in the same test area and other regions (Mannheim, Karlsruhe town, Karlsruhe district, and Germany), (mortality rate: 0.65% [95% confidence interval {CI}, .13%-1.90%] versus 2.16%, 2.32%, 2.48%, 2.82% and 2.76%, respectively, P < .05 for all; hospitalization rate: 14.81% [95% CI, 11.69%-18.40%] versus 6.89%, 6.93%, 6.59%, 6.15%, and 7.22%, respectively, P < .001 for all). The median duration of hospitalization in the CDEW cohort was significantly lower compared with a national sentinel cohort (6 days [interquartile range {IQR}, 4-9.75 days] versus 10 days [IQR, 5-19 days]; Z = -3.156; P = .002). A total of 1.96% patients needed intensive care and 1.09% were mechanically ventilated. Conclusions: The CDEW system significantly reduced COVID-19 mortality and duration of hospitalization and can be applied to the management of future pandemics.

2.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1733250

ABSTRACT

Background The COVID-19 pandemic has caused sudden, severe strain to healthcare systems. Better outpatient management is required to save lives, manage resources effectively and prepare for future pandemics. Methods The Coronataxi digital early warning (CDEW) system deployed in Rhein-Neckar County and Heidelberg, Germany is an outpatient care system consisting of remote digital monitoring via a mobile application, a medical doctor dashboard and medical care delivery to COVID-19 patients in home quarantine when indicated. Patients reported their symptoms, temperature, breathing rate, oxygen saturation, and pulse via the app. This single-center cohort study compared outcomes of the population with and without using the CDEW system. The primary outcome was mortality;the secondary outcomes were hospitalization, duration of hospitalization, intensive care therapy and mechanical ventilation. Results Mortality rate was 3-4-fold lower and hospitalization rate was higher in the CDEW cohort (459 patients) compared to the cohort without CDEW in the same test area and other regions (Mannheim, Karlsruhe town, Karlsruhe district, and Germany), (mortality rate: 0.65% (95%CI: 0.13% - 1.90%) versus 2.16%, 2.32%, 2.48%, 2.82% and 2.76%, respectively, p<.05 for all;hospitalization rate: 14.81% (95%CI: 11.69% - 18.40%) versus 6.89%, 6.93%, 6.59%, 6.15% and 7.22%, respectively, p<.001 for all). The median duration of hospitalization in the CDEW cohort was significantly lower compared to a national sentinel cohort (6(4-9.75) versus 10(5-19) days, Z=-3.156, p=.002). 1.96% patients needed intensive care and 1.09% were mechanically ventilated. Conclusions The CDEW system significantly reduced COVID-19 mortality and duration of hospitalization and can be applied to the management of future pandemics.

3.
Anaesthesist ; 70(8): 662-670, 2021 Aug.
Article in German | MEDLINE | ID: covidwho-1575534

ABSTRACT

BACKGROUND: In the context of sepsis and septic shock, coagulopathy often occurs due to the close relationship between coagulation and inflammation. Sepsis-induced coagulopathy (SIC) is the most severe and potentially fatal form. Anticoagulants used in prophylactic or therapeutic doses are discussed to potentially exert beneficial effects in patients with sepsis and/or SIC; however, due to the lack of evidence recent guidelines are limited to recommendations for drug prophylaxis of venous thromboembolism (VTE), while treatment of SIC has not been addressed. METHODS: In order to determine the status quo of VTE prophylaxis as well as treatment of SIC in German intensive care units (ICU), we conducted a Germany-wide online survey among heads of ICUs from October 2019 to May 2020. In April 2020, the survey was supplemented by an additional block of questions on VTE prophylaxis and SIC treatment in coronavirus disease 2019 (COVID-19) patients. RESULTS: A total of 67 senior doctors took part in the survey. The majority (n = 50; 74.6%) of the responses were from ICU under the direction of an anesthesiologist and/or a department of anesthesiology. Most of the participants worked either at a university hospital (n = 31; 47.8%) or an academic teaching hospital (n = 27; 40.3%). The survey results show a pronounced heterogeneity in clinical practice with respect to the prophylaxis of VTE as well as SIC treatment. In an exemplary case of pneumogenic sepsis, low molecular weight heparins (LMWH) were by far the most frequently mentioned group of medications (n = 51; 76.1% of the responding ITS). In the majority of cases (n = 43; 64.2%), anti-FXa activity is not monitored with the use of LMWH in prophylaxis doses. Unfractionated heparin (UFH) was listed as a strategy for VTE prophylaxis in 37.3% of the responses (n = 25). In an exemplary case of abdominal sepsis 54.5% of the participants (n = 36; multiple answers possible) stated the use of UFH or LMWH and UFH with dosage controlled by PTT is used on two participating ICUs. The anti-FXa activity under prophylactic anticoagulation with LMWH is monitored in 7 participating clinics (10.6%) in abdominal sepsis. Systematic screening for sepsis-associated coagulation disorders does not take place in most hospitals and patterns in the use of anticoagulants show significant variability between ICUs. In the case of COVID-19 patients, it is particularly noticeable that in three quarters of the participating ICUs the practice of drug-based VTE prophylaxis and SIC treatment does not differ from that of non-COVID-19 patients. CONCLUSION: The heterogeneity of answers collected in the survey suggests that a systematic approach to this topic via clinical trials is urgently needed to underline individualized patient care with the necessary evidence.


Subject(s)
Anticoagulants , Blood Coagulation Disorders , Heparin, Low-Molecular-Weight/therapeutic use , Sepsis , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19 , Germany , Heparin/therapeutic use , Humans , Intensive Care Units , Sepsis/complications
4.
J Clin Med ; 10(22)2021 Nov 18.
Article in English | MEDLINE | ID: covidwho-1534109

ABSTRACT

Patient Blood Management advocates an individualized treatment approach, tailored to each patient's needs, in order to reduce unnecessary exposure to allogeneic blood products. The optimization of hemostasis and minimization of blood loss is of high importance when it comes to critical care patients, as coagulopathies are a common phenomenon among them and may significantly impact morbidity and mortality. Treating coagulopathies is complex as thrombotic and hemorrhagic conditions may coexist and the medications at hand to modulate hemostasis can be powerful. The cornerstones of coagulation management are an appropriate patient evaluation, including the individual risk of bleeding weighed against the risk of thrombosis, a proper diagnostic work-up of the coagulopathy's etiology, treatment with targeted therapies, and transfusion of blood product components when clinically indicated in a goal-directed manner. In this article, we will outline various reasons for coagulopathy in critical care patients to highlight the aspects that need special consideration. The treatment options outlined in this article include anticoagulation, anticoagulant reversal, clotting factor concentrates, antifibrinolytic agents, desmopressin, fresh frozen plasma, and platelets. This article outlines concepts with the aim of the minimization of complications associated with coagulopathies in critically ill patients. Hereditary coagulopathies will be omitted in this review.

5.
Med Mycol ; 60(1)2021 Dec 08.
Article in English | MEDLINE | ID: covidwho-1483478

ABSTRACT

Information on invasive aspergillosis (IA) and other invasive filamentous fungal infections is limited in non-neutropenic patients admitted to the intensive care unit (ICU) and presenting with no classic IA risk factors. This review is based on the critical appraisal of relevant literature, on the authors' own experience and on discussions that took place at a consensus conference. It aims to review risk factors favoring aspergillosis in ICU patients, with a special emphasis on often overlooked or neglected conditions. In the ICU patients, corticosteroid use to treat underlying conditions such as chronic obstructive pulmonary disease (COPD), sepsis, or severe COVID-19, represents a cardinal risk factor for IA. Important additional host risk factors are COPD, decompensated cirrhosis, liver failure, and severe viral pneumonia (influenza, COVID-19). Clinical observations indicate that patients admitted to the ICU because of sepsis or acute respiratory distress syndrome are more likely to develop probable or proven IA, suggesting that sepsis could also be a possible direct risk factor for IA, as could small molecule inhibitors used in oncology. There are no recommendations for prophylaxis in ICU patients; posaconazole mold-active primary prophylaxis is used in some centers according to guidelines for other patient populations and IA treatment in critically ill patients is basically the same as in other patient populations. A combined evaluation of clinical signs and imaging, classical biomarkers such as the GM assay, and fungal cultures examination, remain the best option to assess response to treatment. LAY SUMMARY: The use of corticosteroids and the presence of co-morbidities such as chronic obstructive pulmonary disease, acute or chronic advanced liver disease, or severe viral pneumonia caused by influenza or Covid-19, may increase the risk of invasive aspergillosis in intensive care unit patients.


Subject(s)
Aspergillosis , Adrenal Cortex Hormones/adverse effects , Aspergillosis/complications , COVID-19 , Comorbidity , Critical Illness , Humans , Influenza, Human , Intensive Care Units , Liver Diseases , Pulmonary Disease, Chronic Obstructive , Risk Factors , Sepsis
6.
Crit Care Explor ; 3(8): e0517, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1393346

ABSTRACT

IMPORTANCE: Recent evidence suggests a multilevel inflammatory syndrome as a driving factor in some of the most severely ill coronavirus disease 2019 patients with overlapping features to other hyperinflammatory or autoimmune diseases. Therefore, plasma exchange is considered as potential therapy in these patients. OBJECTIVES: We characterize the longitudinal therapeutic efficacy and safety profile of plasma exchange in critically ill patients with clinical and laboratory evidences of coronavirus disease 2019-related immunopathology. DESIGN SETTING AND PARTICIPANTS: A retropsective case-control study of critically ill coronavirus disease 2019 patients treated with plasma exchange at Heidelberg University Hospital between March and December 2020. Plasma exchange-treated patients were compared with coronavirus disease 2019 patients on standard therapy matched for age, gender, disease severity, and features of hyperinflammatory syndrome. MAIN OUTCOME AND MEASURES: Mortality rate and course of clinical and laboratory parameters in response to plasma exchange were assessed in coronavirus disease 2019 patients and in patients on standard care. A plasma volume of 50 mL per kg body weight or a maximum of 4 L was exchanged. RESULTS: In total, 28 critically ill coronavirus disease 2019 patients were treated with a median of three plasma exchange procedures per patient. No relevant complications occurred during plasma exchange therapy. Inflammatory and biochemical markers of end-organ damage and endothelial activation were significantly reduced following plasma exchange together with normalization of body temperature, improved pulmonary function, and reduced vasopressor demand. Most importantly, these improvements were maintained after the last plasma exchange. In contrast, no such effects were observed in the control group, although baseline clinical and laboratory parameters were comparable. Kaplan-Meier analysis showed improved 30-day survival in the plasma exchange group compared with the control group (67.9% vs 42.9%; p = 0.044). In a multivariable analysis, the hazard ratio for death was 0.27 (95% CI, 0.11-0.68; p = 0.005) with plasma exchange versus standard care. CONCLUSIONS AND RELEVANCE: Our data provide further evidence for plasma exchange as a novel therapeutic strategy in a subset of critically ill coronavirus disease 2019 patients by potentially reversing the complex coronavirus disease 2019 immunopathology. Randomized controlled trials are underway to confirm these positive results.

7.
Trials ; 21(1): 828, 2020 Oct 06.
Article in English | MEDLINE | ID: covidwho-1388814

ABSTRACT

OBJECTIVES: Primary objectives • To assess the time from randomisation until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of SARS-CoV-2 infection or standard of care. Secondary objectives • To assess overall survival, and the overall survival rate at 28 56 and 84 days. • To assess SARS-CoV-2 viral clearance and load as well as antibody titres. • To assess the percentage of patients that required mechanical ventilation. • To assess time from randomisation until discharge. TRIAL DESIGN: Randomised, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent plasma or standard of care. PARTICIPANTS: High-risk patients >18 years of age hospitalized with SARS-CoV-2 infection in 10-15 university medical centres will be included. High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at ambient air with additional risk features as categorised in 4 groups: • Group 1, pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less. • Group 2, chronic immunosuppression not meeting the criteria of group 1. • Group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1µg/mL. • Group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2. Observation time for all patients is expected to be at least 3 months after entry into the study. Patients receive convalescent plasma for two days (day 1 and day 2) or standard of care. For patients in the standard arm, cross over is allowed from day 10 in case of not improving or worsening clinical condition. Nose/throat swabs for determination of viral load are collected at day 0 and day 1 (before first CP administration) and subsequently at day 2, 3, 5, 7, 10, 14, 28 or until discharge. Serum for SARS-Cov-2 diagnostic is collected at baseline and subsequently at day 3, 7, 14 and once during the follow-up period (between day 35 and day 84). There is a regular follow-up of 3 months. All discharged patients are followed by regular phone calls. All visits, time points and study assessments are summarized in the Trial Schedule (see full protocol Table 1). All participating trial sites will be supplied with study specific visit worksheets that list all assessments and procedures to be completed at each visit. All findings including clinical and laboratory data are documented by the investigator or an authorized member of the study team in the patient's medical record and in the electronic case report forms (eCRFs). INTERVENTION AND COMPARATOR: This trial will analyze the effects of convalescent plasma from recovered subjects with SARS-CoV-2 antibodies in high-risk patients with SARS-CoV-2 infection. Patients at high risk for a poor outcome due to underlying disease, age or condition as listed above are eligible for enrollment. In addition, eligible patients have a confirmed SARS-CoV-2 infection and O2 saturation ≤ 94% while breathing ambient air. Patients are randomised to receive (experimental arm) or not receive (standard arm) convalescent plasma in two bags (238 - 337 ml plasma each) from different donors (day 1, day 2). A cross over from the standard arm into the experimental arm is possible after day 10 in case of not improving or worsening clinical condition. MAIN OUTCOMES: Primary endpoints: The main purpose of the study is to assess the time from randomisation until an improvement within 84 days defined as two points on a seven-point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of a SARS-CoV-2 infection or standard of care. Secondary endpoints: • Overall survival, defined as the time from randomisation until death from any cause 28-day, 56-day and 84-day overall survival rates. • SARS-CoV-2 viral clearance and load as well as antibody titres. • Requirement mechanical ventilation at any time during hospital stay (yes/no). • Time until discharge from randomisation. • Viral load, changes in antibody titers and cytokine profiles are analysed in an exploratory manner using paired non-parametric tests (before - after treatment). RANDOMISATION: Upon confirmation of eligibility (patients must meet all inclusion criteria and must not meet exclusion criteria described in section 5.3 and 5.4 of the full protocol), the clinical site must contact a centralized internet randomization system ( https://randomizer.at/ ). Patients are randomized using block randomisation to one of the two arms, experimental arm or standard arm, in a 1:1 ratio considering a stratification according to the 4 risk groups (see Participants). BLINDING (MASKING): The study is open-label, no blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total number of 174 patients is required for the entire trial, n=87 per group. TRIAL STATUS: Protocol version 1.2 dated 09/07/2020. A recruitment period of approximately 9 months and an overall study duration of approximately 12 months is anticipated. Recruitment of patients starts in the third quarter of 2020. The study duration of an individual patient is planned to be 3 months. After finishing all study-relevant procedures, therapy, and follow-up period, the patient is followed in terms of routine care and treated if necessary. Total trial duration: 18 months Duration of the clinical phase: 12 months First patient first visit (FPFV): 3rd Quarter 2020 Last patient first visit (LPFV): 2nd Quarter 2021 Last patient last visit (LPLV): 3rd Quarter 2021 Trial Report completed: 4th Quarter 2021 TRIAL REGISTRATION: EudraCT Number: 2020-001632-10, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE , registered on 04/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). The eCRF is attached (Additional file 3).


Subject(s)
Antibodies, Viral/blood , Betacoronavirus , Coronavirus Infections , Pandemics , Plasma/immunology , Pneumonia, Viral , Aged , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , COVID-19 , Clinical Trials, Phase II as Topic , Convalescence , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Female , Humans , Immunization, Passive/methods , Male , Middle Aged , Monitoring, Physiologic/methods , Multicenter Studies as Topic , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Randomized Controlled Trials as Topic , Risk Adjustment , SARS-CoV-2 , Severity of Illness Index
8.
Crit Care ; 25(1): 295, 2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1362062

ABSTRACT

BACKGROUND: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. METHODS: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. RESULTS: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict "survival". Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients' age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. CONCLUSIONS: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration "ClinicalTrials" (clinicaltrials.gov) under NCT04455451.


Subject(s)
COVID-19/epidemiology , Critical Illness/epidemiology , Electronic Health Records/statistics & numerical data , Intensive Care Units , Machine Learning , Adult , Aged , COVID-19/therapy , Cohort Studies , Critical Illness/therapy , Emergency Service, Hospital , Female , Germany , Humans , Male , Middle Aged , Outcome Assessment, Health Care
9.
PLoS Med ; 18(8): e1003735, 2021 08.
Article in English | MEDLINE | ID: covidwho-1354750

ABSTRACT

BACKGROUND: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. METHODS AND FINDINGS: We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers' instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies' heterogeneity in design and reporting. CONCLUSIONS: In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.


Subject(s)
COVID-19 Serological Testing/methods , Age Factors , Antigens, Viral/analysis , COVID-19/diagnosis , COVID-19/etiology , COVID-19 Serological Testing/standards , Carrier State/diagnosis , Carrier State/virology , Humans , Nasopharynx/virology , Reagent Kits, Diagnostic , Reference Standards , SARS-CoV-2/immunology , Sensitivity and Specificity , Viral Load
10.
PLoS One ; 16(7): e0255154, 2021.
Article in English | MEDLINE | ID: covidwho-1331999

ABSTRACT

BACKGROUND: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. METHODS: This systematic review was registered at PROSPERO under CRD42020177154. We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. RESULTS: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10 mg/L, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49 U/L, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88 pg/mL, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 to 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). DISCUSSION: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors that predict severe COVID-19 outcomes and will inform clinical scores to support early decision-making.


Subject(s)
COVID-19/pathology , C-Reactive Protein/metabolism , COVID-19/metabolism , Cerebrovascular Disorders/metabolism , Cerebrovascular Disorders/virology , Fibrin Fibrinogen Degradation Products/metabolism , Humans , L-Lactate Dehydrogenase/metabolism , Troponin I/metabolism
11.
Sci Rep ; 10(1): 19117, 2020 11 05.
Article in English | MEDLINE | ID: covidwho-1242032

ABSTRACT

Podocyte injury has recently been described as unifying feature in idiopathic nephrotic syndromes (INS). Puumala hantavirus (PUUV) infection represents a unique RNA virus-induced renal disease with significant proteinuria. The underlying pathomechanism is unclear. We hypothesized that PUUV infection results in podocyte injury, similar to findings in INS. We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. Hantavirus patients showed significantly increased urinary nephrin, IgG and serum suPAR concentrations compared to healthy controls. Nephrin and IgG levels were significantly higher in patients with severe proteinuria than with mild proteinuria, and nephrin correlated strongly with biomarkers of glomerular proteinuria over time. Congruently, electron microcopy analyses showed a focal podocyte foot process effacement. suPAR correlated significantly with urinary nephrin, IgG and albumin levels, suggesting suPAR as a pathophysiological mediator in podocyte dysfunction. In contrast to INS, proteinuria recovered autonomously in hantavirus patients. This study reveals podocyte injury as main cause of proteinuria in hantavirus patients. A better understanding of the regenerative nature of hantavirus-induced glomerulopathy may generate new therapeutic approaches for INS.


Subject(s)
Glomerular Filtration Barrier/pathology , Hemorrhagic Fever with Renal Syndrome/pathology , Kidney Glomerulus/pathology , Nephrotic Syndrome/pathology , Puumala virus , Adolescent , Adult , Female , Hemorrhagic Fever with Renal Syndrome/blood , Hemorrhagic Fever with Renal Syndrome/urine , Humans , Male , Membrane Proteins/urine , Middle Aged , Nephrotic Syndrome/blood , Nephrotic Syndrome/urine , Podocytes/pathology , Receptors, Urokinase Plasminogen Activator/blood , Young Adult
12.
Lancet Respir Med ; 9(6): 622-642, 2021 06.
Article in English | MEDLINE | ID: covidwho-1219780

ABSTRACT

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.


Subject(s)
COVID-19 , Multiple Organ Failure , SARS-CoV-2/pathogenicity , COVID-19/immunology , COVID-19/physiopathology , Endothelium/physiopathology , Humans , Immunity , Multiple Organ Failure/etiology , Multiple Organ Failure/physiopathology , Patient Acuity , Severity of Illness Index
13.
Ann Intensive Care ; 11(1): 50, 2021 Mar 22.
Article in English | MEDLINE | ID: covidwho-1145459

ABSTRACT

BACKGROUND: COVID-19 pneumonia and subsequent respiratory failure is causing an immense strain on intensive care units globally. Early prediction of severe disease enables clinicians to avoid acute respiratory distress syndrome (ARDS) development and improve management of critically ill patients. The soluble receptor of advanced glycation endproducts (sRAGE) is a biomarker shown to predict ARDS. Although sRAGE level varies depending on the type of disease, there is limited information available on changes in sRAGE levels in COVID-19. Therefore, sRAGE was measured in COVID-19 patients to determine sRAGE level variation in COVID-19 severity and to examine its ability to predict the need for mechanical ventilation (MV) and mortality in COVID-19. METHODS: In this single-centre observational cohort study in Germany, serum sRAGE during acute COVID-19, 20 weeks after the start of COVID-19 symptoms, as well as in control groups of non-COVID-19 pneumonia patients and healthy controls were measured using ELISA. The primary endpoint was severe disease (high-flow nasal oxygen therapy (HFNO)/MV and need of organ support). The secondary endpoints were respiratory failure with need of MV and 30-day mortality. The area under the curve (AUC), cut-off based on Youden's index and odds ratio with 95% CI for sRAGE were calculated with regard to prediction of MV need and mortality. RESULTS: Serum sRAGE in 164 COVID-19 patients, 101 matched COVID-19 convalescent patients, 23 non-COVID-19 pneumonia patients and 15 healthy volunteers were measured. sRAGE level increased with COVID-19 severity, need for oxygen therapy, HFNO/MV, ARDS severity, need of dialysis and catecholamine support, 30-day mortality, sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) score. sRAGE was found to be a good predictor of MV need in COVID-19 inpatients and mortality with an AUC of 0.871 (0.770-0.973) and 0.903 (0.817-0.990), respectively. When adjusted for male gender, age, comorbidity and SOFA score ≥ 3, sRAGE was independently associated with risk of need for HFNO/MV. When adjusted for SOFA score ≥ 3, sRAGE was independently associated with risk of need for MV. CONCLUSIONS: Serum sRAGE concentrations are elevated in COVID-19 patients as disease severity increases. sRAGE should be considered as a biomarker for predicting the need for MV and mortality in COVID-19.

14.
Nat Commun ; 12(1): 1112, 2021 02 18.
Article in English | MEDLINE | ID: covidwho-1091491

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNα and IFNλ levels when compared to non-severe COVID-19 patients. In a mouse model of pulmonary HSV-1 infection, treatment with recombinant IL-3 reduces viral load and mortality. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating pDCs into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells, both, in mice and in COVID-19 negative patients exhibiting pulmonary diseases. This study identifies IL-3 as a predictive disease marker for SARS-CoV-2 infections and as a potential therapeutic target for pulmunory viral infections.


Subject(s)
COVID-19/diagnosis , Interleukin-3/blood , Animals , COVID-19/mortality , Chemokine CXCL12/immunology , Dendritic Cells/cytology , Disease Models, Animal , Female , Germany , Humans , Immunity, Innate , Interferons/blood , Lung/immunology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Prospective Studies , Severity of Illness Index , T-Lymphocytes/cytology , Viral Load
15.
J Clin Med ; 10(1)2021 Jan 02.
Article in English | MEDLINE | ID: covidwho-1011565

ABSTRACT

BACKGROUND: Cardiac manifestation of COVID-19 has been reported during the COVID pandemic. The role of cardiac arrhythmias in COVID-19 is insufficiently understood. This study assesses the incidence of cardiac arrhythmias and their prognostic implications in hospitalized COVID-19-patients. METHODS: A total of 166 patients from eight centers who were hospitalized for COVID-19 from 03/2020-06/2020 were included. Medical records were systematically analyzed for baseline characteristics, biomarkers, cardiac arrhythmias and clinical outcome parameters related to the index hospitalization. Predisposing risk factors for arrhythmias were identified. Furthermore, the influence of arrhythmia on the course of disease and related outcomes was assessed using univariate and multiple regression analyses. RESULTS: Arrhythmias were detected in 20.5% of patients. Atrial fibrillation was the most common arrhythmia. Age and cardiovascular disease were predictors for new-onset arrhythmia. Arrhythmia was associated with a pronounced increase in cardiac biomarkers, prolonged hospitalization, and admission to intensive- or intermediate-care-units, mechanical ventilation and in-hospital mortality. In multiple regression analyses, incident arrhythmia was strongly associated with duration of hospitalization and mechanical ventilation. Cardiovascular disease was associated with increased mortality. CONCLUSIONS: Arrhythmia was the most common cardiac event in association with hospitalization for COVID-19. Older age and cardiovascular disease predisposed for arrhythmia during hospitalization. Whereas in-hospital mortality is affected by underlying cardiovascular conditions, arrhythmia during hospitalization for COVID-19 is independently associated with prolonged hospitalization and mechanical ventilation. Thus, incident arrhythmia may indicate a patient subgroup at risk for a severe course of disease.

16.
World J Emerg Surg ; 15(1): 64, 2020 12 09.
Article in English | MEDLINE | ID: covidwho-968942

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic is a major challenge for health care services worldwide. It's impact on oncologic therapies and elective surgery has been described recently, and the literature provides guidelines regarding appropriate elective patient treatment during the pandemic. However, the impact of SARS-CoV-2 pandemic on emergency surgery services has been poorly investigated up to now. METHODS: A 17-item web survey had been distributed to emergency surgeons in June 2020 around the world, investigating the impact of SARS-CoV-2 pandemic on patients and septic diseases both requiring emergency surgery and the time-to-intervention in emergency surgery routine, as well as experiences with surgery in COVID-19 patients. RESULTS: Ninety-eight collaborators from 31 countries responded to the survey. The majority (65.3%) estimated the impact of the SARS-CoV-2 pandemic on emergency surgical patient care as being strong or very strong. Due to the pandemic, 87.8% reported a decrease in the total number of patients undergoing emergency surgery and approximately 25% estimated a delay of more than 2 h in the time-to-diagnosis and another 2 h in the time-to-intervention. Fifty percent make structural problems with in-hospital logistics (e.g. transport of patients, closed normal wards etc.) mainly responsible for delayed emergency surgery and the frequent need (56.1%) for a triage of emergency surgical patients. 56.1% of the collaborators observed more severe septic abdominal diseases during the pandemic, especially for perforated appendicitis and severe septic cholecystitis (41.8% and 40.2%, respectively). 62.2% had experiences with surgery in COVID-19-infected patients. CONCLUSIONS: The results of The WSES COVID-19 emergency surgery survey are alarming. The combination of an estimated decrease in numbers of emergency surgical patients and an observed increase in more severe septic diseases may be a result of the fear of patients from infection with COVID-19 and a consecutive delayed hospital admission and diagnosis. A critical delay in time-to-diagnosis and time-to-intervention may be a result of changes in in-hospital logistics and operating room as well as intensive care capacities. Both reflect the potentially harmful impact of SARS-CoV-2 pandemic on emergency surgery services.


Subject(s)
COVID-19 , Emergency Service, Hospital/statistics & numerical data , Facilities and Services Utilization/statistics & numerical data , Global Health/statistics & numerical data , Surgical Procedures, Operative/statistics & numerical data , General Surgery/statistics & numerical data , Health Care Surveys , Humans , SARS-CoV-2
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