Many patients with
SARS-CoV-2 infection MESHD develop neurological signs and symptoms, though, 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 MESHD who died and underwent autopsy in our medical center. 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 (ICU). Hospital-associated complications were common, including 8 (20%) with
deep vein thrombosis MESHD/
pulmonary embolism MESHD (DVT/PE), 7 (17%) patients with
acute kidney injury MESHD requiring dialysis, and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 hours 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/ischemic MESHD changes in all brains, both global and focal; large and
small infarcts MESHD, many of which appeared hemorrhagic; 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 MESHD of large arteries and
arteriolosclerosis MESHD, though none had evidence of
vasculitis MESHD. Eighteen (44%) contained pathologies of
neurodegenerative diseases MESHD, 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 (qRT- PCR), RNAscope, and immunocytochemistry with primers, probes, and antibodies directed against the spike and nucleocapsid regions. qRT-PCR revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in nasal epithelia. RNAscope and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in
COVID-19 MESHD 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 rather likely from
systemic inflammation MESHD, perhaps with synergistic contribution from
hypoxia/ischemia MESHD. Further studies are needed to define whether these pathologies, if present in patients who survive
COVID-19 MESHD, might contribute to chronic
neurological problems MESHD.
