Autopsy is an important quality assurance indicator and a tool to advance medical knowledge. This study aims to compare the premortem clinical and postmortem pathology findings in patients who died in the Intensive Care Unit (ICU), to analyze if there are any discrepancies between them, and to compare the results to two similar studies performed in our institution in 2004 and 2007. Between January 1, 2016, and December 31, 2018, 888 patients died in the ICU and 473 underwent post-mortem examination (PME) of whom 437 were included in the present study. Autopsies revealed discrepancies between clinical diagnosis and pathologic findings according to in 101 cases (23.1%) according to Goldman classification. Forty-eight major discrepancies (class I and class II) were identified in 44 cases and the most frequent identified discrepancies were pulmonary embolism (3/12) as class I and malignancies (13/35) as class II. They were more frequent in patients hospitalized for less than 10 days then in the group with more than 10 days of hospitalization (13.8% vs 4.5%; p = 0.002). No statistical difference has been noticed concerning age, gender, and ICU stay. We observed an increase of performed autopsies and a total discrepancy rate similar to the studies performed in the same institution in 2004 (22.5%) and 2007 (21%). In conclusion, discrepancies between clinical and PME diagnoses persist despite the medical progress. Secondly, the autopsy after a short hospital stay may reveal unexpected findings whose diagnosis is challenging even if it may be suspected by the intensivist.

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Introduction COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients who died from COVID-19. However, there is still sparse evidence of virus replication in the human brain, suggesting that neurologic symptoms could be related to mechanisms other than CNS infection by the virus. Our objective was to provide an extensive review of the literature on the neuropathological findings of postmortem brain samples from patients who died from COVID-19 and to report our own experience with 18 postmortem brain samples. Material and methods We used microscopic examination, immunohistochemistry (using two different antibodies) and PCR-based techniques to describe the neuropathological findings and the presence of SARS-CoV-2 virus in postmortem brain samples. For comparison, similar techniques (IHC and PCR) were applied to the lung tissue samples for each patient from our cohort. The systematic literature review was conducted from the beginning of the pandemic in 2019 until June 1st, 2022. Results In our cohort, the most common neuropathological findings were perivascular haemosiderin-laden macrophages and hypoxic-ischaemic changes in neurons, which were found in all cases (n = 18). Only one brain tissue sample harboured SARS-CoV-2 viral spike and nucleocapsid protein expression, while all brain cases harboured SARS-CoV-2 RNA positivity by PCR. A colocalization immunohistochemistry study revealed that SARS-CoV-2 antigens could be located in brain perivascular macrophages. The literature review highlighted that the most frequent neuropathological findings were ischaemic and haemorrhagic lesions, including hypoxic/ischaemic alterations. However, few studies have confirmed the presence of SARS-CoV-2 antigens in brain tissue samples. Conclusion This study highlighted the lack of specific neuropathological alterations in COVID-19-infected patients. There is still no evidence of neurotropism for SARS-CoV-2 in our cohort or in the literature.

Implementation of SARS-CoV-2 testing in the daily practice of pathology laboratories requires procedure adaptation to formalin-fixed and paraffin-embedded (FFPE) samples. So far, one study reported the feasibility of SARS-CoV-2 genome sequencing on FFPE tissues with only one contributory case out of two. The present study aimed to optimize SARS-CoV-2 genome sequencing using the Ion AmpliSeq SARS-CoV-2 Panel on 22 FFPE lung tissues from 16 deceased COVID-19 patients. SARS-CoV-2 was detected in all FFPE blocks using a real-time RT-qPCR targeting the E gene with Crossing Point (Cp) values ranging from 16.02 to 34.16. Sequencing was considered as contributory (i.e. with a uniformity >55%) for 17 FFPE blocks. Adapting the number of target amplification PCR cycles according to the RT-qPCR Cp values allowed to optimize the sequencing quality for the contributory blocks; i.e. 20 PCR cycles for blocks with a Cp value <28 and 25 PCR cycles for blocks with a Cp value between 28 and 30. The majority of blocks with a Cp value >30 were non-contributory. Comparison of matched frozen and FFPE tissues revealed discordance for only three FFPE blocks, all with a Cp value >28. Variant identification and clade classification was possible for 13 patients. The present study validates SARS-CoV-2 genome sequencing on FFPE blocks and opens the possibility to explore correlation between virus genotype and histopathological lesions.