Acute Endotheliitis (Type 3 Hypersensitivity Vasculitis) in Ten COVID-19 Autopsy Brains

Rhodes, Roy H.; Love, Gordon L.; Lameira, Fernanda Da Silve; Shahmirzadi, Maryam Sadough; Fox, Sharon; Heide, Richard S. Vander

doi:10.1101/2021.01.16.21249632

Cited by 15 publications

(11 citation statements)

References 37 publications

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“…Olfactory nerve and brain tissue tested positive for SARS‐CoV‐2 by qRT‐PCR in one case. Other neuropathological findings were reported by Rhodes et al ( 53 ) on a case series of ten patients. At the postmortem examination brain swelling, herniations, intraparenchymal hemorrhages, cerebral infarcts, and cerebral ventriculomegaly were observed.…”

Section: Resultssupporting

confidence: 76%

“…Another hypothesis could be that microgliosis and astrogliosis are secondary to other pathological mechanisms, like infarcts or hemorrhages ( 21 ). In fact, in most studies, ischemic ( 20 , 37 , 38 , 45 , 52 , 53 , 54 , 55 ) and/or hemorrhagic ( 20 , 37 , 38 , 49 , 53 lesions were described, in addition to micro‐ and perivascular hemorrhages ( 20 , 38 , 42 , 45 , 50 , 52 , 54 , 56 and microthrombi ( 38 , 40 , 45 , 49 , 54 . These alterations seem to be related to coagulation disequilibrium and the cytokine storm caused by COVID‐19 ( 8 , 10 , 68 , 69 , 70 ), and not to be a direct consequence of the infection.…”

Section: Discussionmentioning

confidence: 99%

“…The small number of studies so far conducted to investigate histopathological characteristics of COVID‐19 neuro‐involvement did not seem to have highlighted any specific damage of brain tissue directly caused by the virus itself. The described neuropathological findings seem to be more likely because of systemic inflammation and coagulopathy caused by SARS‐CoV‐2 infection, which may lead to a reactive response of CNS components and to the genesis of infarcts, hemorrhages, and microthrombi that are often described in a wide range of brain areas of infected subjects ( 20 , 37 , 38 , 40 , 42 , 45 , 49 , 50 , 52 , 53 , 54 , 55 , 56 ). Further studies are needed to confirm these hypotheses and to better clarify the role of SARS‐CoV‐2 in causing neural damage, to design effective strategies to prevent or at least to control the most fatal consequences of this pandemic disease.…”

Section: Discussionmentioning

confidence: 99%

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SARS‐CoV‐2 and the brain: A review of the current knowledge on neuropathology in COVID‐19

et al. 2021

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SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus responsible for the pandemic disease in the last year, is able to affect the central nervous system (CNS). Compared with its well‐known pulmonary tropism and respiratory complications, little has been studied about SARS‐CoV‐2 neurotropism and pathogenesis of its neurological manifestations, but also about postmortem histopathological findings in the CNS of patients who died from COVID‐19 (coronavirus disease 2019). We present a systematic review, carried out according to the Preferred Reporting Items for Systematic Review standards, of the neuropathological features of COVID‐19. We found 21 scientific papers, the majority of which refer to postmortem examinations; the total amount of cases is 197. Hypoxic changes are the most frequently reported alteration of brain tissue, followed by ischemic and hemorrhagic lesions and reactive astrogliosis and microgliosis. These findings do not seem to be specific to SARS‐CoV‐2 infection, they are more likely because of systemic inflammation and coagulopathy caused by COVID‐19. More studies are needed to confirm this hypothesis and to detect other possible alterations of neural tissue. Brain examination of patients dead from COVID‐19 should be included in a protocol of standardized criteria to perform autopsies on these subjects.

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Section: Resultssupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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SARS‐CoV‐2 and the brain: A review of the current knowledge on neuropathology in COVID‐19

et al. 2021

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“…Mild meningoencephalitis/encephalitis was found in~10% of the cases; this may explain the reported neurologic symptoms/mental status changes reported in a subset of critically ill patients [57]. Rhodes et al [58] reports of a neutrophilic microvascular endothelitis present in variable amounts and variably distributed in the examined brains, suggesting a vasculitis with autoimmune features in 10 patients. Long after recovery from the acute illness and when the virus is no longer present, patients may suffer disabling after-effects that may last for weeks or months.…”

Section: Effects Of Sars-cov-2 In Non-respiratory Organsmentioning

confidence: 92%

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

et al. 2021

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Background Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs. Methods and findings A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings. Conclusions The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

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“…2,27,51 We have also learned that other organs including the kidneys, liver, endocrine organs, the eye, skin, and the central nervous system can be affected by the virus, possibly as a result of direct viral binding to ACE2, or due to immunemediated effects of the disease. 52,53 The common symptoms associated with other organs are related to the respective underlying function and include acute kidney injury, diarrhea, vomiting, and anosmia and ageusia. The effects on the vascular system/endothelium are potentially lethal and include pulmonary embolism, acute myocardial infarction, and stroke.…”

Section: Potential Mechanisms Of Cardiac Injury In Covid-19mentioning

confidence: 99%

COVID-19: The Heart of the Matter—Pathological Changes and a Proposed Mechanism

Fox

Heide

2021

J Cardiovasc Pharmacol Ther

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The SARS-CoV-2 virus has resulted in over 88 million cases worldwide of COVID-19 as of January 2021. The heart is one of the most commonly affected organs in COVID-19, but the nature and extent of the cardiac pathology has remained controversial. It has been shown that patients infected with SARS-CoV-2 can sustain type 1 myocardial infarction in the absence of significant atherosclerotic coronary artery disease. However, many patients present with small elevations of troponin enzymes of unclear etiology which correlate with overall COVID-19 disease outcome. Early autopsy reports indicated variable levels of typical lymphocytic myocarditis, while radiology reports have indicated that myocarditis can be a persistent problem after recovery from acute illness, raising concern about participation in college athletics. In this communication, we review the literature to date regarding the gross and microscopic findings of COVID-19 cardiac involvement, present the findings from over 40 cases from our academic medical center, and propose mechanisms by which patients develop small elevations in troponin.

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Acute Endotheliitis (Type 3 Hypersensitivity Vasculitis) in Ten COVID-19 Autopsy Brains

Cited by 15 publications

References 37 publications

SARS‐CoV‐2 and the brain: A review of the current knowledge on neuropathology in COVID‐19

SARS‐CoV‐2 and the brain: A review of the current knowledge on neuropathology in COVID‐19

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

COVID-19: The Heart of the Matter—Pathological Changes and a Proposed Mechanism

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