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1.
J Virol Methods ; 290: 114093, 2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33549574

RESUMEN

BACKGROUND: In immunocompromised patients, BK Virus (BKV) reactivation may cause serious disease with high morbidity. Particularly for patient management after solid organ transplantation, monitoring of viral load in different clinical specimens is crucial to ensure early diagnosis and response to reactivation. In this study, we evaluated the clinical performance of a custom designed primer /probe set for detection of BKV on the cobas® 6800, a high-throughput platform, employing the open channel of the system for integration of a lab-developed test (LDT). MATERIALS/METHODS: A primer/probe set was optimized for the use on a high-throughput platform. Clinical performance was assessed in EDTA-plasma, serum and urine samples. Limit-of-detection (LOD) was determined by using a dilution series of BKV WHO standard. A CE-labeled PCR test (Altona Diagnostics) was used as a comparison to the assay. RESULTS: The LOD for the LDT BKV assay was 6.7 IU/mL. Inter-and intra-run variability (at 5 x LOD) was low (<1.5 Ct in all specimens). All quality control panel specimens (Instand Germany n = 19) were correctly identified. Of 290 clinical samples tested, results were concordant for 280 samples. Sensitivity and specificity of the assay were 96 % and 98 % respectively. The quantitative analysis revealed a strong correlation (linear regression) between the CE-labelled comparator assay and the new BKV LDT assay with r2 = 0.96 for n = 123 urine samples and r2 = 0.98 for n = 167 plasma/serum samples. CONCLUSION: Compared to a CE-IVD assay, the adapted LDT showed good analytical and clinical sensitivity and specificity for the detection and quantification of BKV in different clinical specimens. It represents a convenient solution to automate the LDT workflow with low hands-on time and thus facilitates high-throughput screening for BKV reactivation in immunocompromised patients.

2.
Artículo en Inglés | MEDLINE | ID: mdl-33585908

RESUMEN

BACKGROUND: The emergence of antibiotic-resistant species calls for fast and reliable phenotypic susceptibility testing to adapt clinical management as fast as possible. OBJECTIVES: We assessed the real-life performance of EUCAST rapid antimicrobial susceptibility testing (RAST) and analysed its impact on patient management. METHODS: RAST was performed on clinical blood cultures containing Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii complex. Categorical agreement with VITEK2 was analysed. A pre-post quasi-experimental observational study was designed to compare antibiotic treatment in sepsis patients in the RAST patient group (n = 51) and a historical control cohort (n = 54). RESULTS: In total, 436 isolates, corresponding to 2314 disc diameters, were measured; 18.4% of these measurements were in the area of technical uncertainty. For the 81.6% categorical results, which could be compared, 94.7% were in agreement, whereas 5.3% of the results were not. In the RAST group, optimal therapy was initiated on the same day as blood culture positivity, while this was the case in the historical group after 24 h. In six cases, RAST allowed for rapid antibiotic escalation. The 30 day mortality rate was lower in the RAST group, although this was not statistically significant. CONCLUSIONS: RAST provides a reliable tool to improve clinical management of sepsis patients by providing rapid phenotypic susceptibility data. While not necessarily being an instrument for de-escalation, especially in areas of low prevalence, early detection allows for timely coverage of resistant isolates. Thus, RAST significantly adds to successful antibiotic stewardship programmes.

3.
Int J Med Microbiol ; 311(2): 151477, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33524636

RESUMEN

OBJECTIVE: We aim to describe the epidemiological, clinical and microbiological characteristics of the linezolid- and vancomycin- resistant Enterococcus faecium (LVRE) in a tertiary care hospital in Germany. METHODS: We conducted a retrospective analysis of 196 LVRE cases observed from 1st January 2012 to 31th December 2018. Patients' medical charts were reviewed and available LVRE (n = 102) were subjected to whole-genome-sequencing. Antibiotic consumption was measured in defined daily dose (DDD)/100 bed-days (BD). RESULTS: The prevalence of LVRE isolates among VRE was 6.3 % in 2018. Most patients had an onco-hematological disease (134/196, 68.4 %). From 2012-2018 an increase of +356.7 % of linezolid defined daily dose/100 bed-days was observed. In 71.4 % (90/126, 70 missing values) of the patients, linezolid was prescribed in the previous 6 months. The median exposure to linezolid was 15 days (Interquartile, IQR 9-23). 42/196 (21.4 %) patients had an LVRE-related infection with an overall 30-day mortality rate of 33 %. In 121/196 (61.7 %) patients, linezolid-susceptible VREfm were isolated before LVRE, suggesting secondary acquisition of linezolid resistance. Genetic analysis revealed that most isolates belonged to ST117 (64/102 available isolates, 62.7 %). The G2576T 23S rDNA mutation was identified as the most common resistance mechanism (96/102, 94.1 %). poxtA was identified in two isolates, while cfr, and optrA were not detected. CONCLUSIONS: Incidence of LVRE related to 23S rDNA mutations is rising and probably associated with antibiotic consumption. Restrictions in the use of linezolid may be needed in order to retain therapeutic options in VRE.


Asunto(s)
Farmacorresistencia Bacteriana , Enterococcus faecium/efectos de los fármacos , Infecciones por Bacterias Grampositivas , Linezolid/farmacología , Resistencia a la Vancomicina , Antibacterianos/farmacología , Enterococcus faecium/genética , Alemania/epidemiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , ARN Ribosómico 23S/genética , Estudios Retrospectivos , Vancomicina
4.
PLoS Pathog ; 17(2): e1009304, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33544760

RESUMEN

S. epidermidis is a substantial component of the human skin microbiota, but also one of the major causes of nosocomial infection in the context of implanted medical devices. We here aimed to advance the understanding of S. epidermidis genotypes and phenotypes conducive to infection establishment. Furthermore, we investigate the adaptation of individual clonal lines to the infection lifestyle based on the detailed analysis of individual S. epidermidis populations of 23 patients suffering from prosthetic joint infection. Analysis of invasive and colonizing S. epidermidis provided evidence that invasive S. epidermidis are characterized by infection-supporting phenotypes (e.g. increased biofilm formation, growth in nutrient poor media and antibiotic resistance), as well as specific genetic traits. The discriminating gene loci were almost exclusively assigned to the mobilome. Here, in addition to IS256 and SCCmec, chromosomally integrated phages was identified for the first time. These phenotypic and genotypic features were more likely present in isolates belonging to sequence type (ST) 2. By comparing seven patient-matched nasal and invasive S. epidermidis isolates belonging to identical genetic lineages, infection-associated phenotypic and genotypic changes were documented. Besides increased biofilm production, the invasive isolates were characterized by better growth in nutrient-poor media and reduced hemolysis. By examining several colonies grown in parallel from each infection, evidence for genetic within-host population heterogeneity was obtained. Importantly, subpopulations carrying IS insertions in agrC, mutations in the acetate kinase (AckA) and deletions in the SCCmec element emerged in several infections. In summary, these results shed light on the multifactorial processes of infection adaptation and demonstrate how S. epidermidis is able to flexibly repurpose and edit factors important for colonization to facilitate survival in hostile infection environments.

5.
Pathologe ; 2021 Feb 16.
Artículo en Alemán | MEDLINE | ID: mdl-33594614

RESUMEN

BACKGROUND: Autopsy is an important tool for understanding the pathogenesis of diseases, including COVID-19. MATERIAL AND METHODS: On 15 April 2020, together with the German Society of Pathology and the Federal Association of German Pathologists, the German Registry of COVID-19 Autopsies (DeRegCOVID) was launched ( www.DeRegCOVID.ukaachen.de ). Building on this, the German Network for Autopsies in Pandemics (DEFEAT PANDEMIcs) was established on 1 September 2020. RESULTS: The main goal of DeRegCOVID is to collect and distribute de facto anonymized data on potentially all autopsies of people who have died from COVID-19 in Germany in order to meet the need for centralized, coordinated, and structured data collection and reporting during the pandemic. The success of the registry strongly depends on the willingness of the respective centers to report the data, which has developed very positively so far and requires special thanks to all participating centers. The rights to own data and biomaterials (stored decentrally) remain with each respective center. The DEFEAT PANDEMIcs network expands on this and aims to strengthen harmonization and standardization as well as nationwide implementation and cooperation in the field of pandemic autopsies. CONCLUSIONS: The extraordinary cooperation in the field of autopsies in Germany during the COVID-19 pandemic is impressively demonstrated by the establishment of DeRegCOVID, the merger of the registry of neuropathology (CNS-COVID19) with DeRegCOVID and the establishment of the autopsy network DEFEAT PANDEMIcs. It gives a strong signal for the necessity, readiness, and expertise to jointly help manage current and future pandemics by autopsy-derived knowledge.

6.
J Med Microbiol ; 70(2)2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33404401

RESUMEN

Introduction. Laboratories worldwide are facing high demand for molecular testing during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which might be further aggravated by the upcoming influenza season in the northern hemisphere.Gap Statement. Given that the symptoms of influenza are largely indistinguishable from those of coronavirus disease 2019 (COVID-19), both SARS-CoV-2 and the influenza viruses require concurrent testing by RT-PCR in patients presenting with symptoms of respiratory tract infection.Aim. We adapted and evaluated a laboratory-developed multiplex RT-PCR assay for simultaneous detection of SARS-CoV-2 (dual target), influenza A and influenza B (SC2/InflA/InflB-UCT) on a fully automated high-throughput system (cobas6800).Methodology. Analytical performance was assessed by serial dilution of quantified reference material and cell culture stocks in transport medium, including pretreatment for chemical inactivation. For clinical evaluation, residual portions of 164 predetermined patient samples containing SARS-CoV-2 (n=52), influenza A (n=43) or influenza B (n=19), as well as a set of negative samples, were subjected to the novel multiplex assay.Results. The assay demonstrated comparable analytical performance to currently available commercial tests, with limits of detection of 94.9 cp ml-1 for SARS-CoV-2, 14.6 cp ml-1 for influenza A and 422.3 cp ml-1 for influenza B. Clinical evaluation showed excellent agreement with the comparator assays (sensitivity of 98.1, 97.7 and 100 % for Sars-CoV-2 and influenza A and B, respectively).Conclusion. The SC2/InflA/InflB-UCT allows for efficient high-throughput testing for all three pathogens and thus provides streamlined diagnostics while conserving resources during the influenza season.

7.
Emerg Infect Dis ; 27(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33327991

RESUMEN

Analyses of infection chains have demonstrated that severe acute respiratory syndrome coronavirus 2 is highly transmissive. However, data on postmortem stability and infectivity are lacking. Our finding of nasopharyngeal viral RNA stability in 79 corpses showed no time-dependent decrease. Maintained infectivity is supported by virus isolation up to 35 hours postmortem.


Asunto(s)
/virología , Nasofaringe/virología , ARN Viral/aislamiento & purificación , Mucosa Respiratoria/virología , /aislamiento & purificación , Cadáver , Humanos
8.
Artículo en Inglés | MEDLINE | ID: mdl-33245470

RESUMEN

Increasing worldwide, prevalence of carbapenem-resistant gram-negative bacteria demands urgent a need for rapid detection and accurate identification of carbapenemases. The BD Phoenix CPO detect (PCD) assay possesses an in-built capacity for parallel susceptibility testing and detection of carbapenemases. Here, the ability of the assay to detect and classify carbapenemase production was tested in a collection of carbapenem-resistant Enterobacterales and non-fermentative gram-negative rods. The ability of the PCD assay to detect and classify carbapenemases was investigated in a collection of 194 clinical, carbapenem-resistant isolates (Enterobacterales [n = 65]; non-fermentative gram-negative rods [n = 129]). AST results were compared to MICS determined by gradient diffusion to determine accuracy of the PCD assay. The accuracy of the PCD assay to detect carbapenemases was compared to the results of molecular isolate characterization using a LDT multiplex carbapenemase PCR assay. All 194 isolates classified as carbapenem-resistant by reference susceptibility testing were also classified correctly as CRO by the PCD assay. Performance analysis of the PCD assay to detect carbapenemase production revealed an overall sensitivity of 98.29% and specificity of 17.95% for the detection of carbapenemase production. For the classification of carbapenemases classes A, B, and D, the PCD correctly classified 79.17% Enterobacterales and 67.16% non-fermentative gram-negative rods. The PCD assay is a reliable tool for the detection of carbapenem resistance and allows for parallel analysis of carbapenemase production. However, while sensitivity is high, low specificity in carbapenemase detection and erroneous classification demands mandatory confirmation by alternative methods, especially in non-fermentative gram-negative bacteria.

10.
mBio ; 11(5)2020 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-33082256

RESUMEN

Although it is normally an innocuous part of the human skin microbiota, Staphylococcus epidermidis has emerged as a major nosocomial pathogen, and implanted foreign materials are an essential risk factor for the development of an infection. The extraordinary efficiency of S. epidermidis to colonize artificial surfaces is particularly related to the ability to form biofilms. Biofilm formation itself critically depends on stable pathogen binding to extracellular host matrix components, e.g. fibronectin (Fn), covering inserted devices in vast amounts. Extracellular matrix binding protein (Embp) and its subdomains referred to as the F-repeat and the FG-repeat are critical for adherence of S. epidermidis to surface-immobilized Fn. Embp-Fn interactions preferentially occur with surface-bound, but not folded, globular Fn via binding to the F3 domain. High-resolution structure analysis of F- and FG-repeats revealed that both repeats are composed of two tightly connected triple α-helix bundles, exhibiting an elongated but rather rigid structural organization in solution. Both F- and FG-repeat possess Fn-binding capacity via interactions with type III subdomain FN12, involving residues within the C and F ß-sheet. FN12 essentially supports stability of the globular Fn state, and thus these findings reasonably explain why Embp-mediated interaction of S. epidermidis necessitates Fn surface immobilization. Thus, Embp employs an uncharacterized bacterial Fn-binding mechanism to promote staphylococcal adherence.IMPORTANCE Staphylococcus epidermidis is a leading pathogen in implant-associated hospital infections. The pathogenesis critically depends on bacterial binding to ECM components, specifically fibronectin (Fn). The cell surface-localized, 1-MDa extracellular matrix binding protein (Embp) is essentially characterized by 10 F- and 40 FG-repeats. These repetitive units, each characterized by two α-helical bundles, organize themselves in a rigid, elongated form. Embp binds preferentially to surface-localized but not soluble Fn, with both F- and FG-repeats being sufficient for Fn binding and resulting bacterial adherence. Binding preferentially involves Fn type III domain, specifically residues of FN12 ß-sheets C and F. Both play key role in stabilizing the globular Fn conformation, explaining the necessity of Fn surface immobilization for a subsequent interaction with Embp. In comparison to many other bacterial Fn-binding proteins using the Fn N terminus, Embp employs a previously undescribed mechanism supporting the adhesion of S. epidermidis to surface-immobilized Fn.

11.
Artículo en Inglés | MEDLINE | ID: mdl-33007476

RESUMEN

OBJECTIVES: Investigation whether in depth characterization of virus variant patterns can be used for epidemiological analysis of the first SARS-CoV-2 infection clusters in Hamburg, Germany. METHODS: Metagenomic RNA- and amplicon-sequencing and subsequent variant calling in 25 respiratory samples from SARS-CoV-2 infected patients involved in the earliest infection clusters in Hamburg. RESULTS: Amplikon sequencing and cluster analyses of these SARS-CoV-2 sequences allowed the identification of the first infection cluster and five non-related infection clusters occurring at the beginning of the viral entry of SARS-CoV-2 in the Hamburg metropolitan region. Viral genomics together with epidemiological analyses revealed that the index patient acquired the infection in Northern Italy and transmitted it to two out of 134 contacts. Single nucleotide polymorphisms clearly distinguished the virus variants of the index and other clusters and allowed to track in which sequences worldwide these mutations were first described. Minor variant analyses identified the transmission of intra-host variants in the index cluster and household clusters. CONCLUSIONS: SARS-CoV-2 variant tracing allows the identification of infection clusters and the follow up of infection chains occurring in the population. Furthermore, the follow up of minor viral variants in infection cluster can provide further resolution on transmission events indistinguishable on consensus sequence level.

12.
Lancet Neurol ; 19(11): 919-929, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33031735

RESUMEN

BACKGROUND: Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. METHODS: In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. FINDINGS: 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70-86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. INTERPRETATION: In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. FUNDING: German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).


Asunto(s)
Betacoronavirus/aislamiento & purificación , Encéfalo/patología , Encéfalo/virología , Infecciones por Coronavirus/patología , Neumonía Viral/patología , Anciano , Anciano de 80 o más Años , Autopsia/métodos , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/genética , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neuropatología , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/genética , Transcriptoma/genética
13.
J Clin Virol ; 132: 104650, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33011643

RESUMEN

BACKGROUND: The ongoing SARS-CoV-2 pandemic presents a unique challenge to diagnostic laboratories. There are preliminary studies correlating qRT-PCR results from different materials to clinical outcomes, yet, comparability is limited due to the plethora of different assays used for diagnostics. In this study we evaluate clinical performance and linear range for the SARS-CoV-2 IVD (cobas6800/8800 system, a fully automated sample-to-result platform) in different clinically relevant matrix materials outside official specifications. METHODS: Assay performance was assessed in human plasma, BAL/BL and transport medium following chemical inactivation. For analytical evaluation, respective matrix materials were spiked with SARS-CoV-2 RNA in ten-fold dilution series. The efficacy of chemical inactivation by guanidine hydrochloride solution was confirmed in cell culture infectivity experiments. For correlation, a total of 289 predetermined clinical samples including respiratory swabs, plasma and lower respiratory tract specimens were subjected to the SARS-CoV-2 IVD test and results were compared. RESULTS: The SARS-CoV-2 IVD showed excellent linearity over four to six log steps depending on matrix material. Chemical inactivation resulted in a reduction in plaque forming units of at least 3.5 log steps, while having no significant impact on assay performance. Inter-run consistency from three different testing sites demonstrated excellent comparability of RT-PCR results (maximum deviation was 1.53 CT). Clinical evaluation for respiratory swabs showed very good agreement with the comparator assay (Positive agreement 95.7 %, negative agreement 98.9 %). CONCLUSION: The SARS-CoV-2 IVD test for the cobas6800/8800 systems offers excellent linear range and inter-run consistency for quantification of SARS-CoV-2 RNA in different matrices outside official specifications.

14.
J Clin Virol ; 130: 104549, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32763809

RESUMEN

BACKGROUND: The global market for SARS-CoV-2-immunoassays is becoming ever more crowded with antibody-tests of various formats, targets and technologies, careful evaluation is crucial for understanding the implications of individual test results. Here, we evaluate the clinical performance of five automated immunoassays on a set of clinical samples. METHODS: Serum/plasma samples of 75 confirmed COVID-19 patients and 320 pre-pandemic serum samples of healthy blood donors were subjected to two IgG and three total antibody SARS-CoV-2-immunoassays. All test setups were automated workflows. RESULTS: Positivity of assays (onset of symptoms > 10 days) ranged between 68.4 % and 81.6 % (Diasorin 68.4 %, Euroimmun 70.3 %, Siemens 73.7 %, Roche 79.0 % and Wantai 81.6 %). All examined assays demonstrated high specificity of >99 % (Euroimmun, Diasorin: 99.1 %, Wantai: 99.4 %) but only two reached levels above 99.5 % (Roche: 99.7 %, Siemens 100 %). Interestingly, there was no overlap in false positive results between the assays. The strongest correlation of quantitative results was observed between the Diasorin and Euroimmun IgG tests (r2 = 0.76). Overall, we observed no difference in the distribution of test results between female and male patients (p-values: 0.18-0.87). A significant difference between severely versus critically ill patients was demonstrated for the Euroimmun, Diasorin, Wantai and Siemens assays (p-values:0.041). CONCLUSION: All assays showed good clinical performance. Our data confirm that orthogonal test strategies as recommended by the CDC can enhance clinical specificity. However, the suboptimal rates of test positivity found at time of hospitalization in this cohort underline the importance of molecular diagnostics to rule out/confirm active infection with SARS-CoV-2.


Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Pruebas Serológicas/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Automatización de Laboratorios , Betacoronavirus , Técnicas de Laboratorio Clínico , Estudios de Cohortes , Infecciones por Coronavirus/inmunología , Reacciones Falso Positivas , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/inmunología , Sensibilidad y Especificidad , Adulto Joven
16.
Microbiol Resour Announc ; 9(23)2020 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-32499358

RESUMEN

Here, we describe the complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from an oropharyngeal swab sample from a female patient with COVID-19 who was infected in Hamburg, northern Germany.

17.
Int J Legal Med ; 134(4): 1275-1284, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32500199

RESUMEN

Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course. Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths. In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany. Our evaluation provides a systematic overview of the first 80 consecutive full autopsies. A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19). In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab. In the other 74 cases, SARS-CoV-2 infection had already been known antemortem. The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years). In the study cohort, 34 deceased were female (38%) and 46 male (62%). Overall, 38% of the deceased were overweight or obese. All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus. A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1-3. Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death. In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism. Peripheral pulmonary artery embolisms were found in nine other cases. Overall, deep vein thrombosis has been found in 40% of the cases. This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/patología , Pulmón/patología , Neumonía Viral/mortalidad , Neumonía Viral/patología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Células Epiteliales Alveolares/patología , Autopsia , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , Comorbilidad , Infección Hospitalaria/mortalidad , Exudados y Transudados , Femenino , Fibroblastos/patología , Fibrosis/patología , Alemania/epidemiología , Células Gigantes/patología , Humanos , Masculino , Megacariocitos/patología , Persona de Mediana Edad , Casas de Salud/estadística & datos numéricos , Tamaño de los Órganos , Sobrepeso/epidemiología , Pandemias , Reacción en Cadena de la Polimerasa , Embolia Pulmonar/patología , Instituciones Residenciales/estadística & datos numéricos , Distribución por Sexo , Enfermedad Relacionada con los Viajes , Trombosis de la Vena/patología
18.
Int J Legal Med ; 134(5): 1977, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32562038

RESUMEN

The affiliation of the author Martin Aepfelbacher was incorrectly assigned in the manuscript. Martin Aepfelbacher is affiliated to the Institute of Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, instead.

20.
Ann Intern Med ; 173(4): 268-277, 2020 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-32374815

RESUMEN

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.


Asunto(s)
Autopsia/métodos , Infecciones por Coronavirus/mortalidad , Neumonía Viral/mortalidad , Embolia Pulmonar/mortalidad , Tromboembolia Venosa/mortalidad , Anciano , Anciano de 80 o más Años , Betacoronavirus , Causas de Muerte , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Prospectivos , Tomografía Computarizada por Rayos X
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