Schneider J, et al.
Postmortem investigation of fatalities following vaccination with COVID-19 vaccines
Int J Legal Med. , https://link.springer.com/article/10.1007%2Fs00414-021-02706-9
CONTENUTO E COMMENTO : Questo studio riporta i dati di indagini post mortem eseguite su 18 persone decedute in seguito a somministrazione di vaccinazione anti COVID-19 (9 con Vaxzevria, 5 con Comirnaty, 3 con Spikevax, e 1 con Janssen), al fine di identificare una possibile relazione causale tra vaccinazione e morte. Tutti i casi sono stati sottoposti ad autopsia completa, analisi istopatologiche e virologiche e ad eventuale diagnostica dell’anafilassi, della trombocitopenia trombotica immunitaria indotta da vaccino (VITT), del metabolismo del glucosio ed esami neuropatologici. In 13 casi la causa del decesso è stata attribuita a patologie pre-esistenti, concordemente con l’assenza di causalità alle indagini post mortem. In quattro casi c’era evidenza macromorfologica di VITT (3 post Vaxzevria e 1 post Janssen), che solo in 2 casi è stata causa probabile di morte; in un caso una miocardite post Cominarty è risultata essere la causa del decesso, con possibile relazione causale con la vaccinazione seppur non dimostrabile oltre ogni ragionevole dubbio. Tali risultati dimostrano la necessità di indagini post mortem sui decessi occorsi post vaccinazione anti COVID-19, non solo autoptiche e istopatologiche ma combinate con esami neuropatologici e diagnostica di laboratorio, al fine di identificare una possibile relazione causale tra vaccinazione e decesso.
Rossana Bussani et al.
Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19
The Journal of Pathology, January 2023; doi.org/10.1002/path.6035
Abstract
SARS-CoV-2 infection is clinically heterogeneous, ranging from asymptomatic to deadly. A few patients with COVID-19 appear to recover from acute viral infection but nevertheless progress in their disease and eventually die, despite persistent negativity at molecular tests for SARS-CoV-2 RNA. Here, we performed post-mortem analyses in 27 consecutive patients who had apparently recovered from COVID-19 but had progressively worsened in their clinical conditions despite repeated viral negativity in nasopharyngeal swabs or bronchioalveolar lavage for 11-300 consecutive days (average: 105.5 days). Three of these patients remained PCR-negative for over 9 months. Post-mortem analysis revealed evidence of diffuse or focal interstitial pneumonia in 23/27 (81%) patients, accompanied by extensive fibrotic substitution in 13 cases (47%). Despite apparent virological remission, lung pathology was similar to that observed in acute COVID-19 individuals, including micro- and macro-vascular thrombosis (67% of cases), vasculitis (24%), squamous metaplasia of the respiratory epithelium (30%), frequent cytological abnormalities and syncytia (67%), and the presence of dysmorphic features in the bronchial cartilage (44%). Consistent with molecular test negativity, SARS-CoV-2 antigens were not detected in the respiratory epithelium. In contrast, antibodies against both spike and nucleocapsid revealed the frequent (70%) infection of bronchial cartilage chondrocytes and para-bronchial gland epithelial cells. In a few patients (19%), we also detected positivity in vascular pericytes and endothelial cells. Quantitative RT-PCR amplification in tissue lysates confirmed the presence of viral RNA. Together, these findings indicate that SARS-CoV-2 infection can persist significantly longer than suggested by standard PCR-negative tests, with specific infection of specific cell types in the lung. Whether these persistently infected cells also play a pathogenic role in long COVID remains to be addressed. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Martínez-Colón G.J. et al.
SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages
Science, September 2022; doi/10.1126/scitranslmed.abm9151
Abstract
Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue–resident macrophages.
Khan M et al
Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients
CELL, November 2022; doi.org/10.1016/j.neuron.2022.11.007
Abstract
Summary Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1 or BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.
S. Krasemann et al.
Assessing and improving the validity of COVID-19 autopsy studies - A multicentreapproach to establishessential standards for immunohistochemical and ultrastructuralanalyses
EBioMedicine, September2022; doi: 10.1016/j.ebiom.2022.104193
Abstract
Autopsy studies haveprovidedvaluable insights into the pathophysiology of COVID-19.
Sincedetection of SARS-CoV-2 in human autopsytissues by IHC and EM isdifficult and frequentlyincorrect, the authors propose criteria for a re-evaluation of available data and guidance for furtherinvestigations of directorganeffects by SARS-CoV-2.
G. J. Martínez-Colón et al.
SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages.
Science Translational Medicine, September 2022; doi: 10.1126/scitranslmed.abm9151
Abstract
To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, the authors evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro.
M. Zacharias et al.
Host and microbiome features of secondary infections in lethal covid-19
iScience, September2022; doi: 10.1016/j.isci.2022.104926
Abstract
Secondary infections contribute significantly to covid-19 mortality but driving factors remain poorly understood. Autopsies of 20 covid-19 cases and 14 controls from the first pandemic wave complemented with microbial cultivation and RNA-seq from lung tissues enabled description of major organ pathologies and specification of secondary infections. Lethal covid-19 segregated into two main death causes with either dominant diffuse alveolar damage (DAD) or secondary pneumonias. The lung microbiome in covid-19 showed a reduced biodiversity and increased prototypical bacterial and fungal pathogens in cases of secondary pneumonias. RNA-seq distinctly mirrored death causes and stratified DAD cases into subgroups with differing cellular compositions identifying myeloid cells, macrophages and complement C1q as strong separating factors suggesting a pathophysiological link. Together with a prominent induction of inhibitory immune-checkpoints our study highlights profound alterations of the lung immunity in covid-19 wherein a reduced antimicrobial defense likely drives development of secondary infections on top of SARS-CoV-2 infection.
e di controllo durante il corso della pandemia.
