Higher Frequency of Acute and Subacute Postmortem Neuropathologic Findings in Patients with COVID-19 Infection

ABSTRACT

Background: Increasing numbers of COVID-19 patients experience acute and chronic neurologic symptoms and complications. Despite ample clinical evidence of CNS involvement by COVID-19, reported neuropathological findings in the postmortem brain tissues of COVID19 patents include variety of hypoxic/ischemic changes, thrombosis, intracerebral and subarachnoid hemorrhage, nonspecific microglial activation and/or lymphocytic infiltration. But, there is no clear evidence whether these findings are specific to COVID19 infection or not. Design: Autopsy brains specimens from 94 COVID19 patients and 61 controls (COVID 19 negative PCR test at time of autopsy) were examined. Clinical data on the presence of comorbid conditions, such as hypertension, diabetes, hyperlipidemia, chronic cardiac, and renal disorders were collected for both groups. Using routine neuropathology approaches, the extents of vascular pathology;acute, subacute, and remote ischemic hemorrhagic lesions;microvascular thrombosis, cerebral edema, and intraparenchymal and subarachnoid hemorrhage were examined. For histopathologic examination hippocampus, frontal and parietal neocortices and white matter, basal ganglia, midbrain, pons, medulla, and cerebellum were selected. Results: Mean age in the COVID19 group was 63 years and 60 years in the control group. There were more males in both group than females (COVID19 - 2.81, Control - 1.51). There was no statistically significant difference between groups in the frequencies of systemic comorbid conditions. 93% of COVID19 cases and 87% of control cases had at least one gross and/or microscopic neuropathologic finding. COVID19 cases showed higher rate of combined acute findings, including brain edema, acute and subacute hypoxic/ischemic lesions, thrombosis, and hemorrhage (61% vs 39%, P value - 0.002). When compared these features separately, none of them reached statistical significance. Arteriolosclerosis (66% vs 66%), atherosclerosis (17% vs 26%), and remote infarcts (19% vs 18%) where quite common findings with similar frequencies in both groups. Conclusions: Our data shows higher tendency of acute and subacute events in the patients with COVID19 infection. These finding do not quite explain the clinical symptoms seen in patients with neurologic complications, and likely represent the sequela of COVID19 systemic complications. More comprehensive neuropathologic and molecular approaches are necessary to better understand the mechanisms of neurologic complications of COVID19 infection.