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1.
Mycoses ; 65(8): 824-833, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1879087

ABSTRACT

BACKGROUND: In the absence of lung biopsy, there are various algorithms for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients that rely on clinical signs, underlying conditions, radiological features and mycology. The aim of the present study was to compare four diagnostic algorithms in their ability to differentiate between probable IPA (i.e., requiring treatment) and colonisation. METHODS: For this diagnostic accuracy study, we included a mixed ICU population with a positive Aspergillus culture from respiratory secretions and applied four different diagnostic algorithms to them. We compared agreement among the four algorithms. In a subgroup of patients with lung tissue histopathology available, we determined the sensitivity and specificity of the single algorithms. RESULTS: A total number of 684 critically ill patients (69% medical/31% surgical) were included between 2005 and 2020. Overall, 79% (n = 543) of patients fulfilled the criteria for probable IPA according to at least one diagnostic algorithm. Only 4% of patients (n = 29) fulfilled the criteria for probable IPA according to all four algorithms. Agreement among the four diagnostic criteria was low (Cohen's kappa 0.07-0.29). From 85 patients with histopathological examination of lung tissue, 40% (n = 34) had confirmed IPA. The new EORTC/MSGERC ICU working group criteria had high specificity (0.59 [0.41-0.75]) and sensitivity (0.73 [0.59-0.85]). CONCLUSIONS: In a cohort of mixed ICU patients, the agreement among four algorithms for the diagnosis of IPA was low. Although improved by the latest diagnostic criteria, the discrimination of invasive fungal infection from Aspergillus colonisation in critically ill patients remains challenging and requires further optimization.


Subject(s)
Invasive Pulmonary Aspergillosis , Aspergillus , Cohort Studies , Critical Illness , Humans , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/microbiology , Sensitivity and Specificity
2.
Viruses ; 14(4)2022 04 14.
Article in English | MEDLINE | ID: covidwho-1792420

ABSTRACT

Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41-4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants/therapeutic use , Autopsy , COVID-19/epidemiology , Critical Illness , Humans , Retrospective Studies , Risk Factors , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
3.
Virchows Arch ; 481(2): 139-159, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1787815

ABSTRACT

The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.


Subject(s)
COVID-19 , Autopsy , Humans , Lung/pathology , Pandemics , SARS-CoV-2
4.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-326246

ABSTRACT

In pathology and legal medicine, the histopathological and microbiological analysis of tissue samples from infected deceased is a valuable information for developing treatment strategies during a pandemic such as COVID-19. However, a conventional autopsy carries the risk of disease transmission and may be rejected by relatives. We propose minimally invasive biopsy with robot assistance under CT guidance to minimize the risk of disease transmission during tissue sampling and to improve accuracy. A flexible robotic system for biopsy sampling is presented, which is applied to human corpses placed inside protective body bags. An automatic planning and decision system estimates optimal insertion point. Heat maps projected onto the segmented skin visualize the distance and angle of insertions and estimate the minimum cost of a puncture while avoiding bone collisions. Further, we test multiple insertion paths concerning feasibility and collisions. A custom end effector is designed for inserting needles and extracting tissue samples under robotic guidance. Our robotic post-mortem biopsy (RPMB) system is evaluated in a study during the COVID-19 pandemic on 20 corpses and 10 tissue targets, 5 of them being infected with SARS-CoV-2. The mean planning time including robot path planning is (5.72+-1.67) s. Mean needle placement accuracy is (7.19+-4.22) mm.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310513

ABSTRACT

Background: Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. Methods: To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. Findings: 84.1% (n=618) were classified as COVID-19 deaths, 6.4% (n=47) as non-COVID-19 deaths, 9.5% (n=70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n=283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%;n=187). Thromboses were found in 39.2% (n=62/158 cases), pulmonary embolism in 22.1% (n=56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n=618) represented COVID-19 deaths. Interpretation Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.

6.
IEEE Trans Med Robot Bionics ; 4(1): 94-105, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1685153

ABSTRACT

In pathology and legal medicine, the histopathological and microbiological analysis of tissue samples from infected deceased is a valuable information for developing treatment strategies during a pandemic such as COVID-19. However, a conventional autopsy carries the risk of disease transmission and may be rejected by relatives. We propose minimally invasive biopsy with robot assistance under CT guidance to minimize the risk of disease transmission during tissue sampling and to improve accuracy. A flexible robotic system for biopsy sampling is presented, which is applied to human corpses placed inside protective body bags. An automatic planning and decision system estimates optimal insertion point. Heat maps projected onto the segmented skin visualize the distance and angle of insertions and estimate the minimum cost of a puncture while avoiding bone collisions. Further, we test multiple insertion paths concerning feasibility and collisions. A custom end effector is designed for inserting needles and extracting tissue samples under robotic guidance. Our robotic post-mortem biopsy (RPMB) system is evaluated in a study during the COVID-19 pandemic on 20 corpses and 10 tissue targets, 5 of them being infected with SARS-CoV-2. The mean planning time including robot path planning is 5.72±167s. Mean needle placement accuracy is 7.19± 422mm.

7.
Virchows Arch ; 480(3): 519-528, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1611405

ABSTRACT

Confronted with an emerging infectious disease at the beginning of the COVID-19 pandemic, the medical community faced concerns regarding the safety of autopsies on those who died of the disease. This attitude has changed, and autopsies are now recognized as indispensable tools for understanding COVID-19, but the true risk of infection to autopsy staff is nevertheless still debated. To clarify the rate of SARS-CoV-2 contamination in personal protective equipment (PPE), swabs were taken at nine points in the PPE of one physician and one assistant after each of 11 full autopsies performed at four centers. Swabs were also obtained from three minimally invasive autopsies (MIAs) conducted at a fifth center. Lung/bronchus swabs of the deceased served as positive controls, and SARS-CoV-2 RNA was detected by real-time RT-PCR. In 9 of 11 full autopsies, PPE samples tested RNA positive through PCR, accounting for 41 of the 198 PPE samples taken (21%). The main contaminated items of the PPE were gloves (64% positive), aprons (50% positive), and the tops of shoes (36% positive) while the fronts of safety goggles, for example, were positive in only 4.5% of the samples, and all the face masks were negative. In MIAs, viral RNA was observed in one sample from a glove but not in other swabs. Infectious virus isolation in cell culture was performed on RNA-positive swabs from the full autopsies. Of all the RNA-positive PPE samples, 21% of the glove samples, taken in 3 of 11 full autopsies, tested positive for infectious virus. In conclusion, PPE was contaminated with viral RNA in 82% of autopsies. In 27% of autopsies, PPE was found to be contaminated even with infectious virus, representing a potential risk of infection to autopsy staff. Adequate PPE and hygiene measures, including appropriate waste deposition, are therefore essential to ensure a safe work environment.


Subject(s)
COVID-19 , Personal Protective Equipment , Autopsy , COVID-19/prevention & control , Humans , Pandemics/prevention & control , RNA, Viral/genetics , SARS-CoV-2
8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-297003

ABSTRACT

Male sex belongs to one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that could affect sex dependent disease outcome are yet unknown. Here, we identified the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (alias aromatase) as a male abundant host factor that contributes to worsened disease outcome in SARS-CoV-2 infected male hamsters. Pulmonary CYP19A1 transcription is further elevated upon viral infection in males correlating with reduced testosterone and increased estradiol levels. Dysregulated circulating sex hormone levels in male golden hamsters are associated with reduced lung function compared to females. Treatment of SARS-CoV-2 infected hamsters with letrozole, a clinically approved CYP19A1 inhibitor, supported recovery of dysregulated plasma sex hormone levels and was associated with improved lung function and health in male but not female animals compared to placebo controls. Whole human exome sequencing data analysis using a Machine Learning approach revealed a CYP19A1 activity increasing mutation being associated with the development of severe COVID-19 for men. In human autopsy-derived lungs CYP19A1 was expressed to higher levels in men who died of COVID-19, at a time point when most viral RNA was cleared. Our findings highlight the role of the lung as a yet unrecognized but critical organ regulating metabolic responses upon respiratory virus infection. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may pose a new therapeutic strategy to reduce poor long-term COVID-19 outcome.

9.
Emerg Infect Dis ; 28(1): 244-247, 2022 01.
Article in English | MEDLINE | ID: covidwho-1496968

ABSTRACT

We investigated the infectivity of 128 severe acute respiratory disease coronavirus 2-associated deaths and evaluated predictive values of standard diagnostic procedures. Maintained infectivity (20%) did not correlate with viral RNA loads but correlated well with anti-S antibody levels. Sensitivity >90% for antigen-detecting rapid diagnostic tests supports their usefulness for assessment.


Subject(s)
COVID-19 , SARS-CoV-2 , Autopsy , Diagnostic Tests, Routine , Humans , Sensitivity and Specificity , Viral Load
10.
Sci Rep ; 11(1): 19342, 2021 09 29.
Article in English | MEDLINE | ID: covidwho-1442803

ABSTRACT

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.


Subject(s)
Autopsy , COVID-19 , Comorbidity , Adult , Age Factors , Aged , Aged, 80 and over , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , COVID-19/diagnosis , COVID-19/epidemiology , Female , Germany/epidemiology , Humans , Lung/pathology , Male , Middle Aged , Mortality , Pneumonia , Prospective Studies , Pulmonary Embolism , SARS-CoV-2 , Thrombosis
11.
Int J Legal Med ; 135(6): 2347-2349, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1391863

ABSTRACT

Due to the development of novel functionalities, distinct SARS-CoV-2 variants such as B.1.1.7 fuel the current pandemic. B.1.1.7 is not only more transmissible, but may also cause an increased mortality compared to previous SARS-CoV-2 variants. Human tissue analysis of the SARS-CoV-2 lineage B.1.1.7 is urgently needed, and we here present autopsy data from 7 consecutive SARS-CoV-2 B.1.1.7 cases. The initial RT-qPCR analyses from nasopharyngeal swabs taken post mortem included typing assays for B.1.1.7. We quantitated SARS-CoV-2 B.1.1.7 viral load in autopsy tissue of multiple organs. Highest levels of SARS-CoV-2 B.1.1.7 copies normalized to ß-globin were detected in the respiratory system (lung and pharynx), followed by the liver and heart. Importantly, SARS-CoV-2 lineage B.1.1.7 was found in 100% of cases in the lungs and in 85.7% in pharynx tissue. Detection also in the kidney and brain highlighting a pronounced organ tropism. Comparison of the given results to a former cohort of SARS-CoV-2 deaths during the first wave in spring 2020 showed resembling organ tropism. Our results indicate that also SARS-CoV-2 B.1.1.7 has a relevant organ tropism beyond the respiratory tract. We speculate that B.1.1.7 spike protein's affinity to human ACE2 facilitates transmission, organ tropism, and ultimately morbidity and mortality. Further studies and larger cohorts are obligatory to proof this link.


Subject(s)
SARS-CoV-2/physiology , Viral Load , Viral Tropism , Aged , Autopsy , Female , Heart/virology , Humans , Kidney/virology , Liver/virology , Lung/virology , Male , Middle Aged , Pharynx/virology
12.
Int J Legal Med ; 134(5): 1977, 2020 09.
Article in English | MEDLINE | ID: covidwho-1384415

ABSTRACT

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.

14.
Forensic Sci Med Pathol ; 17(3): 411-418, 2021 09.
Article in English | MEDLINE | ID: covidwho-1252221

ABSTRACT

The body of a deceased with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is considered infectious. In this study, we present the results of infectivity testing of the body and testing of mortuary staff for SARS-CoV-2. We performed real-time quantitative polymerase chain reaction (RT-qPCR) for SARS-CoV-2 on 33 decedents with ante mortem confirmed SARS-CoV-2 infection. Swabs of the body surface from five different body regions and from the body bag or coffin were examined. A subset of the swabs was brought into cell culture. In addition, screening of 25 Institute of Legal Medicine (ILM) personnel for ongoing or past SARS-CoV-2 infection was performed at two different time points during the pandemic. Swabs from all locations of the body surface and the body environment were negative in cases of negative post mortem nasopharyngeal testing (n=9). When the post mortem nasopharyngeal swab tested positive (n=24), between 0 and 5 of the body surface swabs were also positive, primarily the perioral region. In six of the cases, the body bag also yielded a positive result. The longest postmortem interval with positive SARS-CoV-2 RT-qPCR at the body surface was nine days. In no case viable SARS-CoV-2 was found on the skin of the bodies or the body bags. One employee (autopsy technician) had possible occupational infection with SARS-CoV-2; all other employees were tested negative for SARS-CoV-2 RNA or antibody twice. Our data indicate that with adequate management of general safety precautions, transmission of SARS-CoV-2 through autopsies and handling of bodies is unlikely.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Nasopharynx , Pandemics , RNA, Viral
15.
Rechtsmedizin (Berl) ; 31(5): 427-433, 2021.
Article in German | MEDLINE | ID: covidwho-1202737

ABSTRACT

Background: In the context of the COVID-19-pandemic, mortality and incidence are key determinants to assess the transmission dynamics and the resulting potential threat. Systematic microbiological monitoring of deaths provides a fundamental basis to particularly assess underrecording of community-acquired mortality. It should be further elucidated whether a death cohort of previously unreported cases may be structurally different from the cohort of officially registered cases. Methods: A systematic reverse transcription (RT) qPCR testing for SARS-CoV­2 infections from nasopharyngeal swab samples was carried out. A representative sample of corpses from crematoria and the Institute of Legal Medicine of the Federal State of Hamburg were included. A comparative analysis of primarily reported and unreported fatalities in an 8­week period after occurrence of the first pandemic-related deaths in Hamburg was performed. Results: A total of 1231 deaths were included, all of which were previously unsuspicious for SARS-CoV­2 infection. Thereof 29 cases of previously unknown infections were recorded. In the first phase of the pandemic, incidental findings predominantly occurred among younger people from domestic environments with unclear or unnatural manner of death at the Institute of Legal Medicine. Over time, incidental findings investigated at the crematoria increased, mostly related to nursing home residents. The overall cohort showed no significant sociodemographic differences to a comparative collective of known SARS-CoV­2-associated deaths. Primarily unreported cases showed a significantly lower proportion of COVID-19 as the underlying cause of death. Conclusion: A systematic PCR-based monitoring of deaths allows a more targeted detection and classification of SARS-CoV­2 positive cases. A preventive contribution can be made by disclosing unreported pandemic-related cases of death.

16.
Emerg Infect Dis ; 27(1)2021 01.
Article in English | MEDLINE | ID: covidwho-983633

ABSTRACT

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.


Subject(s)
COVID-19/virology , Nasopharynx/virology , RNA, Viral/isolation & purification , Respiratory Mucosa/virology , SARS-CoV-2/isolation & purification , Cadaver , Humans
17.
Lancet Neurol ; 19(11): 919-929, 2020 11.
Article in English | MEDLINE | ID: covidwho-813939

ABSTRACT

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).


Subject(s)
Betacoronavirus/isolation & purification , Brain/pathology , Brain/virology , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Aged , Aged, 80 and over , Autopsy/methods , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/genetics , Female , Germany/epidemiology , Humans , Male , Middle Aged , Neuropathology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/genetics , SARS-CoV-2 , Transcriptome/genetics
18.
Ann Intern Med ; 173(4): 268-277, 2020 08 18.
Article in English | MEDLINE | ID: covidwho-782419

ABSTRACT

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.


Subject(s)
Autopsy/methods , Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Pulmonary Embolism/mortality , Venous Thromboembolism/mortality , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cause of Death , Female , Germany/epidemiology , Humans , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
19.
Virchows Arch ; 477(3): 335-339, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-646463

ABSTRACT

Clinical characterization of COVID-19 (Corona Virus Disease 2019) is being performed worldwide to gain insights into the pathogenesis and course of the disease. Little is known regarding morphological findings, which are essential to understanding the unique features and pathomechanisms of the disease, from which one can identify possible new treatments. It has been shown that diffuse alveolar damage, signifying acute respiratory distress syndrome, is present together with atypical multinucleated cells in reported cases of the disease by Tian et al. (J Thorac Oncol 15:700-704, 2020). Macroscopic morphological findings in COVID-19 remain elusive to this day. Here, we report the case of the first German to die due to COVID-19. A detailed examination consisting of full-body computed tomography, autopsy, histology assessment, and viral assessment has been performed. The lungs of the deceased contained high concentrations of SARS-CoV-2 RNA and displayed the typical radiological signatures of COVID-19. Furthermore, a morphological pattern was found displaying hyperaemic areas interspersed by normally perfused areas affecting the whole lung. We also report a finding suggestive of micro-thrombotic events in the lung, which is compatible with the recently described coagulation changes and increased incidence of pulmonary artery embolisms seen in COVID-19 patients as reported by Wichmann et al. (Ann Intern Med, 2020). A broader study is needed to confirm these findings.


Subject(s)
Coronavirus Infections/pathology , Lung Diseases/pathology , Lung Diseases/virology , Pneumonia, Viral/pathology , Pulmonary Alveoli/pathology , Autopsy , Betacoronavirus , COVID-19 , Germany , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , Thrombosis/pathology , Thrombosis/virology
20.
Int J Legal Med ; 134(4): 1275-1284, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-526787

ABSTRACT

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.


Subject(s)
Betacoronavirus , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Lung/pathology , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Age Distribution , Aged , Aged, 80 and over , Alveolar Epithelial Cells/pathology , Autopsy , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Comorbidity , Cross Infection/mortality , Exudates and Transudates , Female , Fibroblasts/pathology , Fibrosis/pathology , Germany/epidemiology , Giant Cells/pathology , Humans , Male , Megakaryocytes/pathology , Middle Aged , Nursing Homes/statistics & numerical data , Organ Size , Overweight/epidemiology , Pandemics , Polymerase Chain Reaction , Pulmonary Embolism/pathology , Residential Facilities/statistics & numerical data , SARS-CoV-2 , Sex Distribution , Travel-Related Illness , Venous Thrombosis/pathology
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