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1.
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.

2.
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.

4.
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
5.
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
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