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1.
J Infect Dis ; 224(3): 389-394, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338710

ABSTRACT

BACKGROUND: Postmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific. METHODS: We investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death. RESULTS: Postmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)-related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31-13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate. CONCLUSION: Postmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Respiratory System/virology , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2 , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/virology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Postmortem Changes , Sensitivity and Specificity , Young Adult
2.
J Cell Mol Med ; 25(14): 7001-7012, 2021 07.
Article in English | MEDLINE | ID: covidwho-1276684

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in many deaths throughout the world. It is vital to identify the novel prognostic biomarkers and therapeutic targets to assist with the subsequent diagnosis and treatment plan to mitigate the expansion of COVID-19. Since angiotensin-converting enzyme 2 (ACE2)-positive cells are hosts for COVID-19, we focussed on this cell type to explore the underlying mechanisms of COVID-19. In this study, we identified that ACE2-positive cells from the bronchoalveolar lavage fluid (BALF) of patients with COVID-19 belong to bronchial epithelial cells. Comparing with patients of COVID-19 showing severe symptoms, the antigen processing and presentation pathway was increased and 12 typical genes, HLA-DRB5, HLA-DRB1, CD74, HLA-DRA, HLA-DPA1, HLA-DQA1, HSP90AA1, HSP90AB1, HLA-DPB1, HLA-DQB1, HLA-DQA2, and HLA-DMA, particularly HLA-DPB1, were obviously up-regulated in ACE2-positive bronchial epithelial cells of patients with mild disease. We further discovered SDCBP was positively correlated with above 12 genes particularly with HLA-DPB1 in ACE2-positive bronchial epithelial cells of COVID-19 patients. Moreover, SDCBP may increase the immune infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in different lung carcinoma. Moreover, we found the expression of SDCBP was positively correlated with the expression of antigen processing and presentation genes in post-mortem lung biopsies tissues, which is consistent with previous discoveries. These results suggest that SDCBP has good potential to be further developed as a novel diagnostic and therapeutic target in the treatment of COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Bronchi/pathology , COVID-19/pathology , Epithelial Cells/metabolism , RNA-Seq , Severity of Illness Index , Single-Cell Analysis , Syntenins/metabolism , Antigen Presentation/genetics , Bronchoalveolar Lavage Fluid , COVID-19/genetics , COVID-19/metabolism , Epithelial Cells/pathology , Gene Expression Profiling , Humans , Postmortem Changes , SARS-CoV-2/physiology , Up-Regulation/genetics
3.
J Infect Dis ; 224(3): 389-394, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1231036

ABSTRACT

BACKGROUND: Postmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific. METHODS: We investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death. RESULTS: Postmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)-related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31-13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate. CONCLUSION: Postmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Respiratory System/virology , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2 , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/virology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Postmortem Changes , Sensitivity and Specificity , Young Adult
4.
Neurology ; 95(14): e2016-e2027, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-1105774

ABSTRACT

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuroinvasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. METHODS: In this prospective, monocentric, case series study, consecutive patients who fulfilled the following inclusion criteria benefited from an early postmortem structural brain MRI: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest CT scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. RESULTS: Among the 62 patients who died of COVID-19 from March 31, 2020, to April 24, 2020, at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical microbleeds and macrobleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES; 1 decedent), and nonspecific deep white matter changes (1 decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed. CONCLUSIONS: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. Brainstem MRI findings do not support a brain-related contribution to respiratory distress in COVID-19.


Subject(s)
Brain Edema/diagnostic imaging , Brain/diagnostic imaging , Cerebral Hemorrhage/diagnostic imaging , Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Diffusion Magnetic Resonance Imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Olfactory Bulb/diagnostic imaging , Pandemics , Postmortem Changes , Prospective Studies , SARS-CoV-2 , White Matter/diagnostic imaging
5.
Med Leg J ; 89(1): 40-53, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1039970

ABSTRACT

The activity of the SARS-CoV-2 virus has not yet been studied in a post-mortem setting. The absence of these data has led to the prohibition of exposure of infected corpses during burial procedures. Our aim was to assess the virus's persistence and the possibility of transmission in the post-mortem phase including autopsy staff. The sample group included 29 patients who were admitted to our Covid-19 Centre who died during hospitalisation and the autopsy staff. All the swabs were subjected to a one-step real-time reverse transcription polymerase chain reaction with cycle threshold (Ct) values. Swab collection was performed at 2 h, 4 h, 6 h, 12 h, over 24 since death. The following were the analysis of patients' swabs: 10 cases were positive 2 h after death; 10 cases positive 4 h after death; 9 cases were found positive 6 h after death; 7 cases positive 12 h after death; 9 cases remained positive 24 h after death. The swabs performed on all the forensic pathologist staff on duty who performed the autopsies were negative. The choice to avoid rituals and the display of corpses before and at the burial procedures given appears cautiously valid due to the persistence of the SARS-CoV-2 virus in the post-mortem period. Although the caution in choosing whether or not to perform an autopsy on infected corpses is acceptable, not to perform autopsies is not biologically supported.


Subject(s)
Autopsy , COVID-19/transmission , Cadaver , Postmortem Changes , SARS-CoV-2/pathogenicity , Adult , Aged , Aged, 80 and over , Female , Humans , Italy/epidemiology , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Young Adult
6.
J Forensic Sci ; 65(6): 2194-2197, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1024180

ABSTRACT

Various infectious diseases, including COVID-19, MERS, and tuberculosis, are global public health issues. Tuberculosis, which is caused by Mycobacterium tuberculosis (MTB), is highly contagious and can be transmitted through inhalation of the bacteria. However, it has been assumed that the infectiousness of bacteria and viruses in dead bodies weakens as the time from death increases. In particular, there is little awareness of infection control measures concerning decomposed bodies or even the need for such measures. The deceased, in whom we discovered MTB 3 months following her death, was a woman in her 80s who died at home. We performed judicial autopsy, because police suspected homicide when her husband hanged himself. Obtained organs were used for microscopic examination by hematoxylin-eosin staining and Ziehl-Neelsen staining. In addition, real-time PCR and mycobacterial culture testing using Ogawa's medium were performed for the detection of MTB. We found that the MTB in the decomposed body remained viable and potentially infectious. To identify the bacterial strain further, we performed DNA-DNA hybridization and identified the strain as MTB complex. Potentially infectious live MTB survived in the dead body far longer than had been previously reported. Pathologists should consider microbial culture tests for all autopsied cases in which the decedent's medical history or macro-examination suggests possible infection, even when a long duration of time has passed since death. Pathologists and specialists who perform autopsies should recognize that all dead bodies are potentially infectious, including those in which long periods have elapsed since death.


Subject(s)
Lung/microbiology , Lung/pathology , Microbial Viability , Mycobacterium tuberculosis/isolation & purification , Postmortem Changes , Aged, 80 and over , Autopsy , Female , Humans , Time Factors , Tuberculosis, Pulmonary/diagnosis
7.
J Exp Med ; 218(3)2021 03 01.
Article in English | MEDLINE | ID: covidwho-968998

ABSTRACT

Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1ß, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.


Subject(s)
COVID-19/pathology , COVID-19/virology , Inflammasomes/metabolism , SARS-CoV-2/physiology , Severity of Illness Index , Apoptosis , Comorbidity , Cytokines/biosynthesis , Humans , Lung/pathology , Monocytes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Postmortem Changes , Treatment Outcome
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