What can we learn from brain autopsies in COVID-19?

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) for which there have been over 50 million confirmed cases and 1.2 million deaths globally. While many SARS-CoV-2 infected individuals are asymptomatic or experience respiratory symptoms, extrapulmonary manifestations, including neurological symptoms and conditions, are increasingly recognized. There remains no clear understanding of the mechanisms that underlie neurological symptoms in COVID-19 and whether SARS-CoV-2 has the potential for neuroinvasion in humans. In this minireview, we discuss what is known from human autopsies in fatal COVID-19, including highlighting studies that investigate for the presence of SARS-CoV-2 in brain and olfactory tissue, and summarize the neuropathological consequences of infection. Incorporating microscopic and molecular findings from brain tissue into what we know about clinical disease will inform best practice management guidance and direct research priorities as it relates to neurological morbidity from COVID-19.

Keywords: Brain autopsies; COVID-19; Immunohistochemistry; Neuropathogenesis; Neuropathology; Reverse transcriptase polymerase chain reaction; SARS-CoV-2.

Fig. 1

Neuropathological findings of COVID-19. (A) Coronal brain slice from a 55 year old man who died from COVID-19 contains a calcified nodule (arrow) in the right globus pallidus, but is otherwise unremarkable. (B) Hematoxylin and eosin stained section of hippocampus shows scattered hypereosinophilic neurons indicative of acute hypoxic injury. (C) Hematoxylin and eosin stained section shows extravasated red blood cells suggestive of microhemorrhage (deep pink). (D) CD45 immunostaining (brown) highlights a small collection of perivascular immune cells. (E) CD45 immunostaining (brown) also highlights numerous resident immune cells of the brain parenchyma (microglia). (F) In comparison to panel E, a patient without COVID-19 shows minimal CD45 immunostaining (brown). (G) SARS-CoV-2 nucleocapsid immunohistochemistry (brown) shows a cytoplasmic staining pattern in respiratory epithelial cells of the trachea. (H) Transmission electron micrograph of SARS-CoV-2 from cultured cells shows spherical extracellular viral particles (arrows). Images B-F taken at 200x magnification, G at 400x magnification, and are each from a different patient. Image H is from the Centers for Disease Control and Prevents Public Health Image Library, courtesy of Courtesy Cynthia S. Goldsmith and A. Tamin.