Acute Brain Ischemia, Infarction and Hemorrhage in Subjects Dying with or Without Autopsy-Proven Acute Pneumonia

Beach, Thomas G.; Sue, Lucia I.; Intorcia, Anthony; Glass, Michael J.; Walker, Jessica E; Arce, Richard; Nelson, Courtney M.; Serrano, Geidy E.

doi:10.1101/2021.03.22.21254139

Cited by 5 publications

(4 citation statements)

References 99 publications

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“…An important issue is whether or not COVID-19 lower respiratory disease elicits more intense systemic repercussions than typical acute pneumonia. Our investigations ( 112 , 156 , 162 ) indicate that acute or subacute ischemic changes, infarctions or hemorrhages are probably not more common in COVID-19 than they are in subjects dying without COVID-19 or with or without non-COVID-19 acute pneumonia. Early adoption of low molecular weight heparin therapy may have reduced thromboembolism in our study subjects, in comparison with COVID-19 decedents in the first few months of the pandemic.…”

Section: Discussionmentioning

confidence: 58%

“…Microvascular, acute and subacute ischemic, and/or hemorrhagic lesions ( 4 , 11 , 13 , 20 , 26 , 30 , 33 , 35 , 36 , 38 , 39 , 45–50 , 53–62 ) have frequently been reported in COVID-19 but these are also common in unselected autopsy series. We found that acute and subacute ischemia, infarction, and hemorrhage were present in the brains of up to 14% of 691 consecutive pre-COVID-19 autopsies with or without concurrent autopsy-proven pneumonia ( 162 ). In comparison, in reviews of COVID-19 publications, reported clinically determined rates of acute brain infarction or hemorrhage range from 0.5% to 20% ( 1 , 4 , 5 , 13 , 25 , 26 , 28 , 29 , 32 , 34–36 , 38 , 39 , 45–48 , 53–55 , 156 , 163–175 ).…”

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19

Serrano¹,

Walker²,

Tremblay³

et al. 2022

Journal of Neuropathology &Amp; Experimental Neurology

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Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19

Serrano¹,

Walker²,

Tremblay³

et al. 2022

Journal of Neuropathology &Amp; Experimental Neurology

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“…Respiratory failure in COVID-19 certainly worsens the initial status of the patient but may be associated with other pulmonary diseases. The study by Beach et al aimed at comparing the incidence of ischemic and hemorrhagic stroke in patients with pneumonia and COVID-19 with that of ACVA in other pneumonias not associated with COVID-19 showed a similar risk of ACVA in patients of both groups [33]. The role of associated coagulopathies cannot be excluded.…”

Section: Ischemic Stroke In Covid-19mentioning

confidence: 99%

Morphologic Findings in the Cerebral Cortex in COVID-19: Association of Microglial Changes with Clinical and Demographic Variables

et al. 2023

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Despite the enormous interest in COVID-19, there is no clear understanding of the mechanisms underlying the neurological symptoms in COVID-19. Microglia have been hypothesized to be a potential mediator of the neurological manifestations associated with COVID-19. In most existing studies to date, morphological changes in internal organs, including the brain, are considered in isolation from clinical data and defined as a consequence of COVID-19. We performed histological immunohistochemical (IHC) studies of brain autopsy materials of 18 patients who had died from COVID-19. We evaluated the relationship of microglial changes with the clinical and demographic characteristics of the patients. The results revealed neuronal alterations and circulatory disturbances. We found an inverse correlation between the integral density Iba-1 (microglia/macrophage-specific marker) IHC staining and the duration of the disease (R = −0.81, p = 0.001), which may indicate a reduced activity of microglia and do not exclude their damage in the long-term course of COVID-19. The integral density of Iba-1 IHC staining was not associated with other clinical and demographic factors. We observed a significantly higher number of microglial cells in close contact with neurons in female patients, which confirms gender differences in the course of the disease, indicating the need to study the disease from the standpoint of personalized medicine.

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“…Одною з локацій взаємодії вірусу SARS-CoV-2 з ACE2 є нюховий епітелій в носовій порожнині з наступним проникненням вірусу через ґратчасту пластинку біля нюхової цибулини, що спостерігається при ізольованій аносмії чи агевзії з респіраторними симптомами або без них [27,28]. На думку науковців з Національного інституту США з проблем старіння пряме інфікування нейронів головного мозку вірусом SARS-CoV-2 є вкрай рідкісним явищем, тоді як більшість неврологічних наслідків може бути наслідком сепсису, коагулопатії, гіперімунної реакції або поліорганної недостатності [29].…”

Section: вступunclassified

Retrospective Analysis of Coronavirus Disease Lethal Cases

Kindrativ¹,

Vasylyk²,

Matskevych³

et al. 2021

Fiziol Zh

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There was performed a statistical analysis of 164 records of pathological examination of persons who died of coronavirus disease during April-November, 2020. It is determined that the share of males was 62.20%, and females – 37.80%; the average age of the deceased persons was 64.40 ± 13.79 years. The largest number of lethal cases (57.32%) falls on the age category of 60-79 years, and the smallest (6.71%) – on the age category of 20-39 years. It is important that men predominate in all age groups. The most common direct causes of death were: respiratory failure – 78.05%, multiorgan failure – 17.07%. At the same time, respiratory insufficiency was dominant in all age categories, while the share of multiorgan failure was the largest in the group of persons aged 20-39 years. As a result of the analysis of thromboembolic complications found in 10.37% of cases, there were 3.05% of cases of acute coronary syndrome and acute cerebrovascular disorder, 1.83% of cases – acute thrombosis of the arteries of the lower extremities, 1.22% of cases – acute thrombosis of the mesenteric vessels, and 0.61% – disseminated intravascular coagulation of blood and acute pulmonary thromboembolism. Morphological examination of the lung tissue of the deceased persons revealed signs of diffuse alveolar damage involving the microcirculatory bed vessels in the pathological process. According to the results of bacteriological examination of the lungs there were revealed some signs of bacterial infection in 51.83% of cases, and signs of fungal infection – in 15.85% of cases. The most common (23.78%) was the growth of Klebsiella pneumoniae. The most common comorbidities were: coronary heart disease – 62.20%, hypertension – 29.27%, non-insulin dependent diabetes mellitus – 11.59%, obesity – 10.37%, anemia – 6.71% and chronic obstructive pulmonary disease – 2.44%. In 10.98% of cases diabetes was the main underlying disease. The data obtained may indicate an adverse effect of these diseases on the course of coronavirus disease.

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Acute Brain Ischemia, Infarction and Hemorrhage in Subjects Dying with or Without Autopsy-Proven Acute Pneumonia

Cited by 5 publications

References 99 publications

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19

Morphologic Findings in the Cerebral Cortex in COVID-19: Association of Microglial Changes with Clinical and Demographic Variables

Retrospective Analysis of Coronavirus Disease Lethal Cases

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