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.  

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).         

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: