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1.
Viruses ; 14(4)2022 Apr 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
2.
Eur J Immunol ; 2022 Apr 13.
Article in English | MEDLINE | ID: covidwho-1782587

ABSTRACT

COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic. While immune responses of the adaptive immune system have been in the focus of research, the role of NK cells in COVID-19 remains less well understood. Here, we characterized NK cell-mediated SARS-CoV-2 antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 spike-1 (S1) and nucleocapsid (NC) protein. Serum samples from SARS-CoV-2 resolvers induced significant CD107a-expression by NK cells in response to S1 and NC, while serum samples from SARS-CoV-2-negative individuals did not. Furthermore, serum samples from individuals that received the BNT162b2 vaccine induced strong CD107a expression by NK cells that increased with the second vaccination and was significantly higher than observed in infected individuals. As expected, vaccine-induced responses were only directed against S1 and not against NC protein. S1-specific CD107a responses by NK cells were significantly correlated to NK cell-mediated killing of S1-expressing cells. Interestingly, screening of serum samples collected prior to the COVID-19 pandemic identified two individuals with cross-reactive antibodies against SARS-CoV-2 S1, which also induced degranulation of NK cells. Taken together, these data demonstrate that antibodies induced by SARS-CoV-2 infection and anti-SARS-CoV-2 vaccines can trigger significant NK cell-mediated ADCC activity, and identify some cross-reactive ADCC-activity against SARS-CoV-2 by endemic coronavirus-specific antibodies.

3.
Stem Cell Reports ; 17(2): 307-320, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1712991

ABSTRACT

Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients' brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, we found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.


Subject(s)
Blood-Brain Barrier/virology , Central Nervous System/virology , SARS-CoV-2/physiology , Virus Internalization , Antibodies/pharmacology , Benzamidines/pharmacology , COVID-19/pathology , COVID-19/virology , Endothelial Cells/cytology , Endothelial Cells/metabolism , Endothelial Cells/virology , Guanidines/pharmacology , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Models, Biological , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Virus Internalization/drug effects
4.
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.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314512

ABSTRACT

Neurological complications are common in COVID-19 patients. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in patients’ brain tissues, its entry routes and resulting consequences are not well understood. Here, we report that the blood-brain barrier (BBB) and its microenvironment show pronounced upregulation of interferon signaling pathways in fatal COVID-19. Moreover, human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) were susceptible to SARS-CoV-2 infection and recapitulated the transcriptional changes detected in vivo . While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active transcytosis of the virus across the BBB in vitro . SARS-CoV-2 entry into BCECs could be reduced by anti-spike-, anti-ACE2- and anti-NRP1-specific antibodies or the TMPRSS2 inhibitor nafamostat. Together, our data provide direct evidence for SARS-CoV-2 brain entry across the BBB resulting in an increase in interferon signaling.

7.
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.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296455

ABSTRACT

Obesity increases the risk for poor outcome in patients with coronavirus disease-19 (COVID-19). However, the role of adipose tissue for viral propagation and potential metabolic implications are not understood. We detected SARS-CoV-2 in adipose tissue of overweight but not lean male COVID-19 patients. SARS-CoV-2 replicates to high titres in cultured mature adipocytes, a process depending on lipid accumulation and mobilization. After intranasal inoculation, we observed high viral replication in fat depots of Golden Syrian hamsters, demonstrating dissemination from the respiratory tract and subsequent propagation in adipose tissue. Following induction of pro-inflammatory responses, expression of de novo lipogenesis enzymes was suppressed in adipose tissue. This specific down-regulation was reflected by lipidomic alterations in plasma of SARS-CoV-2 infected hamsters as well as in hospitalized COVID-19 patients. Overall, our study highlights that adipose tissue is an important site of SARS-CoV-2 replication, contributing to dysregulation of systemic lipid metabolism.<br><br>Funding: This study was supported by a rapid response grant from the Federal Ministry of Health (BMG;ZMV I 1-2520COR501 to GG), by DFG grants SCHE522/4-1 (LS) and SFB1328, project- ID:335447727 (JH). As part of the National Network University Medicine (NUM) funded by the Federal Ministry of Education and Research (BMBF, Germany), this work was funded within the research consortium DEFEAT PANDEMIcs, grant number 01KX2021 (FH, PL, KP, BO).<br><br>Declaration of Interests: The authors declare no competing interests.<br><br>Ethics Approval Statement: The Ethics Committee of the Hamburg Chamber of Physicians reviewed and approved the studies (PV7311, 2020-10353-BO-ff, WF-051/20, WF-053/20). For the preparation of primary human white adipocytes, biopsies of subcutaneous and visceral adipose tissues were taken during bariatric surgery at the Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf. All participants signed an informed consent and the study was approved by the Ethics Committee of the Hamburg Chamber of Physicians (PV4889).

10.
Open Forum Infect Dis ; 8(11): ofab509, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1526187

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA loads in patient specimens may act as a clinical outcome predictor in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: We evaluated the predictive value of viral RNA loads and courses in the blood compared with the upper and lower respiratory tract loads of critically ill COVID-19 patients. Daily specimen collection and viral RNA quantification by reverse transcription quantitative polymerase chain reaction were performed in all consecutive 170 COVID-19 patients between March 2020 and February 2021 during the entire intensive care unit (ICU) stay (4145 samples analyzed). Patients were grouped according to their 90-day outcome as survivors (n=100) or nonsurvivors (n=70). RESULTS: In nonsurvivors, blood SARS-CoV-2 RNA loads were significantly higher at the time of admission to the ICU (P=.0009). Failure of blood RNA clearance was observed in 33/50 (66%) of the nonsurvivors compared with 12/64 (19%) survivors (P<.0001). As determined by multivariate analysis, taking sociodemographic and clinical parameters into account, blood SARS-CoV-2 RNA load represents a valid and independent predictor of outcome in critically ill COVID-19 patients (odds ratio [OR; log10], 0.23; 95% CI, 0.12-0.42; P<.0001), with a significantly higher effect for survival compared with respiratory tract SARS-CoV-2 RNA loads (OR [log10], 0.75; 95% CI, 0.66-0.85; P<.0001). Blood RNA loads exceeding 2.51×103 SARS-CoV-2 RNA copies/mL were found to indicate a 50% probability of death. Consistently, 29/33 (88%) nonsurvivors with failure of virus clearance exceeded this cutoff value constantly. CONCLUSIONS: Blood SARS-CoV-2 load is an important independent outcome predictor and should be further evaluated for treatment allocation and patient monitoring.

11.
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
12.
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
13.
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
14.
BMC Health Serv Res ; 21(1): 317, 2021 Apr 07.
Article in English | MEDLINE | ID: covidwho-1388757

ABSTRACT

BACKGROUND: To identify the determinants of health care use among homeless individuals. METHODS: Data were taken from the Hamburg survey of homeless individuals (n = 100 individuals in the here used model, mean age 44.8 years, SD 12.5) focusing on homeless individuals in Hamburg, Germany. The number of physician visits in the past 3 months and hospitalization in the preceding 12 months were used as outcome measures. Drawing on the Andersen model of health care use as a conceptual framework, predisposing characteristics, enabling resources and need factors as well as psychosocial variables were included as correlates. RESULTS: Negative binomial regressions showed that increased physician visits were associated with being female (IRR: 4.02 [95% CI: 1.60-10.11]), absence of chronic alcohol consume (IRR: 0.26 [95% CI: 0.12-0.57]) and lower health-related quality of life (IRR: 0.97 [95% CI: 0.96-0.98]). Furthermore, logistic regressions showed that the likelihood of hospitalization was positively associated with lower age (OR: 0.93 [95% CI: 0.89-0.98]), having health insurance (OR: 8.11 [2.11-30.80]) and lower health-related quality of life (OR: 0.97 [95% CI: 0.94-0.99]). CONCLUSIONS: Our study showed that predisposing characteristics (both age and sex), enabling resources (i.e., health insurance) and need factors in terms of health-related quality of life are main drivers of health care use among homeless individuals. This knowledge may assist in managing health care use.


Subject(s)
COVID-19 , Health Services Accessibility , Homeless Persons , Patient Acceptance of Health Care/psychology , Adult , Delivery of Health Care , Female , Germany/epidemiology , Homeless Persons/psychology , Humans , Male , Quality of Life , SARS-CoV-2 , Surveys and Questionnaires
15.
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.

16.
Risk Manag Healthc Policy ; 14: 2689-2695, 2021.
Article in English | MEDLINE | ID: covidwho-1290601

ABSTRACT

PURPOSE: To clarify the prevalence and determinants of fear of COVID-19 among homeless individuals during the COVID-19 pandemic. PATIENTS AND METHODS: Data were taken from the Hamburg survey of homeless individuals (n=150) covering homeless adults in Hamburg, Germany. Multiple linear regressions were used. Beyond sociodemographic and lifestyle-related independent variables, COVID-19-related factors were also used as independent variables. RESULTS: In sum, 56.2% of homeless individuals reported no fear of COVID-19, 23.8% reported a little fear of COVID-19, 9.2% reported some fear of COVID-19 and 10.8% reported severe fear of COVID-19. Regressions showed that an increased fear of COVID-19 was significantly associated with younger age (ß=-.01, p<0.05), absence of chronic alcohol consume (ß=-.55, p<0.01), an increased perceived own risk of getting infected with the coronavirus one day (ß=0.42, p<0.001) and a higher agreement that a diagnosis of the coronavirus would ruin his/her life (ß=0.13, p<0.01). CONCLUSION: Given the poor hygienic conditions and their increased vulnerability, data surprisingly suggest a quite low fear of COVID-19 among homeless individuals. Efforts may be beneficial which contribute to thinking rationally about COVID-19 among homeless people, since low levels of fear of COVID-19 may contribute to careless behavior and can lead to super-spreading events.

17.
Am J Pathol ; 191(7): 1193-1208, 2021 07.
Article in English | MEDLINE | ID: covidwho-1283899

ABSTRACT

Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-ß1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Core Binding Factor Alpha 2 Subunit/antagonists & inhibitors , Furin/metabolism , Lung/drug effects , Pulmonary Fibrosis/drug therapy , Animals , Bleomycin , Cells, Cultured , Disease Models, Animal , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Lung/metabolism , Lung/pathology , Male , Mice , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Treatment Outcome
18.
Int J Legal Med ; 136(1): 193-202, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1258202

ABSTRACT

The current pandemic with Severe acute respiratory syndrome-coronavirus-2 has been taking on new dynamics since the emergence of new variants last fall, some of them spreading more rapidly. Many countries currently find themselves in a race to ramp up vaccination strategies that have been initiated and a possible third wave of the pandemic from new variants, such as the Variant of Concern-202012/01 from the B.1.1.7 lineage. Until today, many investigations in death cases of Coronavirus-disease-19 have been conducted, revealing pulmonary damage to be the predominant feature of the disease. Thereby, different degrees of macroscopic and microscopic lung damage have been reported, most of them resembling an Acute Respiratory Distress Syndrome. Far more, systemic complications of the disease such as pulmonary embolisms have been described. However, neither morphologic nor virologic findings of patients dying of the new variants have yet been reported. Here, we report on a comprehensive analysis of radiologic, morphologic, and virologic findings in a fatal case of this variant.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/virology , Fatal Outcome , Humans , Pandemics
19.
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
20.
Am J Pathol ; 191(7): 1193-1208, 2021 07.
Article in English | MEDLINE | ID: covidwho-1242859

ABSTRACT

Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-ß1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Core Binding Factor Alpha 2 Subunit/antagonists & inhibitors , Furin/metabolism , Lung/drug effects , Pulmonary Fibrosis/drug therapy , Animals , Bleomycin , Cells, Cultured , Disease Models, Animal , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Lung/metabolism , Lung/pathology , Male , Mice , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Treatment Outcome
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