Abstract Details Title Coronavirus 2019: Clinicopathological Update Topic Infectious Disease Presentation(s) S21 - Acute and Post-Acute Sequelae of COVID-19 (4:18 PM-4:30 PM) Poster/Presentation Number 005 Background 144 cases of COVID-19 revealed 5 salient findings: First, elevated serum cytokines and procoagulant levels due to the cytokine storm increases risk of thrombotic infarcts and a likelihood of leptomeningeal, cerebral or brainstem parenchymal inflammatory. Second, SARS-CoV-2 reactivity in olfactory bulb neurons and glial cells lends support to a route of viral CNS entry. Third, rare cases exhibit acute demyelinating features and indolent brainstem encephalitis, which may be a challenge in differentiating them in life from critical illness encephalopathy. Fourth, hypoxia-ischemia, so noted in 19% would not likely account for other neuropathological changes. Fifth, there were no pediatric cases despite known fatal childhood multisystem inflammatory syndrome (MIS-C). Objective To update the clinicopathological aspects in confirmed cases of COVID-19 due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in children and adults. Design/Methods Sixty-four cases including 5 pediatric and 59 adults, increases the present cohort to 208 postmortem COVID-19 cases. Results First, 9 cases of fatal pediatric cases (infancy to <18 years) alone (3 cases) or associated with MIS-C (4 cases), meningoencephalitis or small vessel primary CNS angiitis (in 1 each), coincided with elevated levels of cytokines and procoagulants. Notwithstanding the levels are increased compared to normal in a ratio of 4:1. Second, interstitial brainstem inflammation and focal perivascular parenchymal T-cell infiltrates are found in 15% and 12% of cases respectively in the combined cohort, increased from 7% and 5% in the earlier cohort. Third, both SARS-CoV-2 reactivity in brain sections noted in 20%, and hypoxia-ischemia in 23% did not change significantly compared to the earlier cohort that respectively found 17% and 19%. Fourth, the absence of fatal COVID-19 cases associated with vaccination and effective early intervention. Conclusions Postmortem brain findings together with the clinical disease will inform best neurological practice management and research priorities into prevention and cure of present and future COVID-19 neurological illness. Authors/Disclosures David S. Younger, MD, DrPH, MPH, MS PRESENTER Dr. Younger has nothing to disclose.