[Infectiousness of SARS-CoV-2 positive corpses during external post mortem examination].
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ABSTRACT:
SUBMITTER: Verhoff MA
PROVIDER: S-EPMC8214379 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The inflammasome complex is a key part of chronic diseases and acute infections, being responsible for cytokine release and cell death mechanism regulation. The SARS-CoV-2 infection is characterized by a dysregulated cytokine release. In this context, the inflammasome complex analysis within SARS-CoV-2 infection may prove beneficial to understand the disease's mechanisms. Post-mortem minimally invasive autopsies were performed in patients who died from COVID-19 (n = 24), and lung samples were compared to a patient control group (n = 11) and an Influenza A virus H1N1 subtype group from the 2009 pandemics (n = 10). Histological analysis was performed using hematoxylin-eosin staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: ACE2, TLR4, NF-κB, NLRP-3 (or NALP), IL-1β, IL-18, ASC, CASP1, CASP9, GSDMD, NOX4, TNF-α. Data obtained from digital analysis underwent appropriate statistical tests. IHC analysis showed biomarkers that indicate inflammasome activation (ACE2; NF-κB; NOX4; ASC) were significantly increased in the COVID-19 group (p < 0.05 for all) and biomarkers that indicate cell pyroptosis and inflammasome derived cytokines such as IL-18 (p < 0.005) and CASP1 were greatly increased (p < 0.0001) even when compared to the H1N1 group. We propose that the SARS-CoV-2 pathogenesis is connected to the inflammasome complex activation. Further studies are still warranted to elucidate the pathophysiology of the disease.
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Project description:ImportanceAssessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD).MethodsConsecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels.ResultsCOVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis.ConclusionsVast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.
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Project description:SARS-CoV-2 breakthrough infections in vaccinated individuals and reinfections among previously infected individuals have become increasingly common. Such infections highlight a broader need to understand the contribution of vaccination, including booster doses, and natural immunity to the infectiousness of persons with SARS-CoV-2 infections, especially in high-risk populations with intense transmission such as prisons. Here, we show that both vaccine-derived and naturally acquired immunity independently reduce the infectiousness of persons with Omicron variant SARS-CoV-2 infections in a prison setting. Analyzing SARS-CoV-2 surveillance data from December 2021 to May 2022 across 35 California state prisons with a predominately male population, we estimate that unvaccinated Omicron cases had a 36% (95% confidence interval (CI): 31-42%) risk of transmitting infection to close contacts, as compared to 28% (25-31%) risk among vaccinated cases. In adjusted analyses, we estimated that any vaccination, prior infection alone, and both vaccination and prior infection reduced an index case's risk of transmitting infection by 22% (6-36%), 23% (3-39%) and 40% (20-55%), respectively. Receipt of booster doses and more recent vaccination further reduced infectiousness among vaccinated cases. These findings suggest that although vaccinated and/or previously infected individuals remain highly infectious upon SARS-CoV-2 infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection, underscoring some benefit of vaccination to reduce but not eliminate transmission.
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Project description:PurposeTo detect SARS-CoV-2 RNA in post-mortem human eyes. Ocular symptoms are common in patients with COVID-19. In some cases, they can occur before the onset of respiratory and other symptoms. Accordingly, SARS-CoV-2 RNA has been detected in conjunctival samples and tear film of patients suffering from COVID-19. However, the detection and clinical relevance of intravitreal SARS-CoV-2 RNA still remain unclear due to so far contradictory reports in the literature.MethodsIn our study 20 patients with confirmed diagnosis of COVID-19 were evaluated post-mortem to assess the conjunctival and intraocular presence of SARS-CoV-2 RNA using sterile pulmonary and conjunctival swabs as well as intravitreal biopsies (IVB) via needle puncture. SARS-CoV-2 PCR and whole genome sequencing from the samples of the deceased patients were performed. Medical history and comorbidities of all subjects were recorded and analyzed for correlations with viral data.ResultsSARS-CoV-2 RNA was detected in 10 conjunctival (50%) and 6 vitreal (30%) samples. SARS-CoV-2 whole genome sequencing showed the distribution of cases largely reflecting the frequency of circulating lineages in the Munich area at the time of examination with no preponderance of specific variants. Especially there was no association between the presence of SARS-CoV-2 RNA in IVBs and infection with the variant of concern (VOC) alpha. Viral load in bronchial samples correlated positively with load in conjunctiva but not the vitreous.ConclusionSARS-CoV-2 RNA can be detected post mortem in conjunctival tissues and IVBs. This is relevant to the planning of ophthalmologic surgical procedures in COVID-19 patients, such as pars plana vitrectomy or corneal transplantation. Furthermore, not only during surgery but also in an outpatient setting it is important to emphasize the need for personal protection in order to avoid infection and spreading of SARS-CoV-2. Prospective studies are needed, especially to determine the clinical relevance of conjunctival and intravitreal SARS-CoV-2 detection concerning intraocular affection in active COVID-19 state and in post-COVID syndrome.
| S-EPMC8713040 | biostudies-literature
Project description:The Coronavirus Disease 19 (COVID-19) pandemic has caused an unexpected death toll worldwide. Even though several guidelines for the management of infectious corpses have been proposed, the limited number of post-mortem analyses during the pandemic has led to inaccuracies in the counting of COVID-19 deaths and contributed to a lack of important information about the pathophysiology of the SARS-CoV-2 infection. Due to the impossibility of carrying out autopsies on all corpses, the scientific community has raised the question of whether confirmatory analyses could be performed on exhumed bodies after a long period of burial to assess the presence of SARS-CoV-2 RNA. Post-mortem lung samples were collected from 16 patients who died from COVID-19 infection and were buried for a long period of time. A custom RNA extraction protocol was developed to enhance extraction of viral RNA from degraded samples and highly sensitive molecular methods, including RT-qPCR and droplet digital PCR (ddPCR), were used to detect the presence of SARS-CoV-2 RNA. The custom extraction protocol developed allowed us to extract total RNA effectively from all lung samples collected. SARS-CoV-2 viral RNA was effectively detected in all samples by both RT-qPCR and ddPCR, regardless of the length of burial. ddPCR results confirmed the persistence of the virus in this anatomical niche and revealed high viral loads in some lung samples, suggesting active infection at the time of death. To the best of our knowledge, this is the first study to demonstrate the persistence of SARS-CoV-2 viral RNA in the lung even after a long post-mortem interval (up to 78 days). The extraction protocol herein described, and the highly sensitive molecular analyses performed, could represent the standard procedures for SARS-CoV-2 detection in degraded lung specimens. Finally, the innovative results obtained encourage post-mortem confirmatory analyses even after a long post-mortem interval.
| S-EPMC8304625 | biostudies-literature
Project description:A majority of SARS-CoV-2 infections are transmitted from a minority of infected subjects, some of which may be symptomatic or pre-symptomatic. We aimed to quantify potential infectiousness among asymptomatic healthcare workers (HCWs) in relation to prior or later symptomatic disease. We previously (at the onset of the SARS-CoV-2 epidemic) performed a cohort study of SARS-CoV-2 infections among 27,000 healthcare workers (HCWs) at work in the capital region of Sweden. We performed both SARS-CoV-2 RT-PCR and serology. Furthermore, the cohort was comprehensively followed for sick leave, both before and after sampling. In the present report, we used the cohort database to quantify potential infectiousness among HCWs at work. Those who had sick leave either before or after sampling were classified as post-symptomatic or pre-symptomatic, whereas the virus-positive subjects with no sick leave were considered asymptomatic. About 0.2% (19/9449) of HCW at work were potentially infectious and pre-symptomatic (later had disease) and 0.17% (16/9449) were potentially infectious and asymptomatic (never had sick leave either before nor after sampling). Thus, 33% and 28% of all the 57 potentially infectious subjects were pre-symptomatic or asymptomatic, respectively. When a questionnaire was administered to HCWs with past infection, only 10,5% of HCWs had had no indication at all of having had SARS-CoV-2 infection ("truly asymptomatic"). Our findings provide a unique quantification of the different groups of asymptomatic, potentially infectious HCWs.
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Project description:High viral titers of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected in human corpses long after death. However, little is known about the kinetics of infectious SARS-CoV-2 in corpses. In this case series study, we investigated the postmortem kinetics of infectious SARS-CoV-2 in human corpses by collecting nasopharyngeal swab samples at multiple time points from six SARS-CoV-2-infected patients after their death. SARS-CoV-2 RNA was detected by quantitative reverse transcription-polymerase chain reaction from nasopharyngeal swab samples collected from all six deceased patients. A viral culture showed the presence of infectious virus in one deceased patient up to 12 days after death. Notably, this patient had a shorter time from symptom onset to death than the other patients, and autopsy samples showed pathological findings consistent with viral replication in the upper respiratory tract. Therefore, this patient died during the viral shedding phase, and the amount of infectious virus in the corpse did not decrease over time up to the date of autopsy (12 days after death). The findings of this study indicate that the persistence of SARS-CoV-2 in corpses can vary among individuals and may be associated with the stage of the disease at the time of death. These important results complement many previously reported findings on the infectivity of SARS-CoV-2 at postmortem.
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Project description:Post-mortem examination plays a pivotal role in understanding the pathobiology of the SARS-CoV-2; thus, the optimization of virus detection on the post-mortem formalin-fixed paraffin-embedded (FFPE) tissue is needed. Different techniques are available for the identification of the SARS-CoV-2, including reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy. The main goal of this study is to compare ISH versus RT-PCR to detect SARS-CoV-2 on post-mortem lung samples of positive deceased subjects. A total of 27 samples were analyzed by RT-PCR targeting different viral RNA sequences of SARS-CoV-2, including envelope (E), nucleocapsid (N), spike (S), and open reading frame (ORF1ab) genes and ISH targeting S and Orf1ab. All 27 cases showed the N gene amplification, 22 out of 27 the E gene amplification, 26 out of 27 the S gene amplification, and only 6 the ORF1ab gene amplification. The S ISH was positive only in 12 out of 26 cases positive by RT-PCR. The S ISH positive cases with strong and diffuse staining showed a correlation with low values of the number of the amplification cycles by S RT-PCR suggesting that ISH is a sensitive assay mainly in cases carrying high levels of S RNA. In conclusion, our findings demonstrated that ISH assay has lower sensitivity to detect SARS-CoV-2 in FFPE compared to RT-PCR; however, it is able to localize the virus in the cellular context since it preserves the morphology.
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Project description:In the present study, we evaluated post-mortem lateral cerebral ventricle (LCV) changes using computed tomography (CT). Subsequent periodical CT scans termed "sequential scans" were obtained for three cadavers. The first scan was performed immediately after the body was transferred from the emergency room to the institute of legal medicine. Sequential scans were obtained and evaluated for 24 h at maximum. The time of death had been determined in the emergency room. The sequential scans enabled us to observe periodical post-mortem changes in CT images. The series of continuous LCV images obtained up to 24 h (two cases)/16 h (1 case) after death was evaluated. The average Hounsfield units (HU) within the LCVs progressively increased, and LCV volume progressively decreased over time. The HU in the cerebrospinal fluid (CSF) increased at an individual rate proportional to the post-mortem interval (PMI). Thus, an early longitudinal radiodensity change in the CSF could be potential indicator of post-mortem interval (PMI). Sequential imaging scans reveal post-mortem changes in the CSF space which may reflect post-mortem brain alterations. Further studies are needed to evaluate the proposed CSF change markers in correlation with other validated PMI indicators.
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Project description:ObjectivesTo summarise the evidence on the duration of infectiousness of individuals in whom SARS-CoV-2 ribonucleic acid is detected.MethodsA rapid review was undertaken in PubMed, Europe PubMed Central and EMBASE from 1 January 2020 to 26 August 2020.ResultsWe identified 15 relevant studies, including 13 virus culture and 2 contact tracing studies. For 5 virus culture studies, the last day on which SARS-CoV-2 was isolated occurred within 10 days of symptom onset. For another 5 studies, SARS-CoV-2 was isolated beyond day 10 for approximately 3% of included patients. The remaining 3 virus culture studies included patients with severe or critical disease; SARS-CoV-2 was isolated up to day 32 in one study. Two studies identified immunocompromised patients from whom SARS-CoV-2 was isolated for up to 20 days. Both contact tracing studies, when close contacts were first exposed greater than 5 days after symptom onset in the index case, found no evidence of laboratory-confirmed onward transmission of SARS-CoV-2.ConclusionCOVID-19 patients with mild-to-moderate illness are highly unlikely to be infectious beyond 10 days of symptoms. However, evidence from a limited number of studies indicates that patients with severe-to-critical illness or who are immunocompromised, may shed infectious virus for longer.
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