COVID-19 Neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital
Autor: | Carla Y. Kim, Alexander M. Chong, Anna S. Nordvig, Kurenai Tanji, Peter Canoll, Phyllis L. Faust, Michael D. Glendinning, Jonathan B. Overdevest, Kiran T. Thakur, Yang Liu, Allison Soung, Anne Catrin Uhlemann, Richard A. Hickman, Gul Moonis, Gunnar Hargus, Chun Chieh Lin, Robyn S. Klein, Emily Happy Miller, Serge Przedborski, Alexandra Boubour, Morgan L. Prust, William Roth, Dritan Agalliu, Samuel L. Bruce, Matei A. Banu, Sachin Jambawalikar, Angela Lignelli-Dipple, Amelia K. Boehme, James E. Goldman, Alexander G. Khandji, Jan Claassen, Osama Al-Dalahmah, Andrew F. Teich, Michael L Miller |
---|---|
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Pathology T-Lymphocytes Bacteremia Autopsy 0302 clinical medicine microglial nodules Aged 80 and over Neurons Venous Thrombosis Reverse Transcriptase Polymerase Chain Reaction AcademicSubjects/SCI01870 Acute kidney injury Brain Acute Kidney Injury Middle Aged Thrombosis Pulmonary embolism Survival Rate Intensive Care Units Hypoxia-Ischemia Brain Spike Glycoprotein Coronavirus RNA Viral Female Original Article Microglia Vasculitis Intracranial Hemorrhages Adult Brain Infarction medicine.medical_specialty microglia activation Ischemia Arteriolosclerosis Neuropathology 03 medical and health sciences Phagocytosis Renal Dialysis medicine Coronavirus Nucleocapsid Proteins Humans Aged Inflammation neuropathology SARS-CoV-2 business.industry COVID-19 Phosphoproteins medicine.disease 030104 developmental biology AcademicSubjects/MED00310 Neurology (clinical) Pulmonary Embolism business 030217 neurology & neurosurgery |
Zdroj: | Brain |
Popis: | Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38–97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20–30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems. |
Databáze: | OpenAIRE |
Externí odkaz: |