key: cord-300923-5cyxr98s
authors: Younger, David S
title: Postmortem Neuropathology in Covid‐19
date: 2020-10-23
journal: Brain Pathol
DOI: 10.1111/bpa.12915
sha: 
doc_id: 300923
cord_uid: 5cyxr98s

This study concerns the clinicopathologic correlation of 50 decedents of 2019 coronavirus disease (Covid‐19) due to severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) from among 250 reported patients succumbing to Covid‐19 illness (1‐7) who underwent detailed postmortem neuropathological studies. This disease, which starts in the lungs, is a multisystem disorder affecting all major organs including the brain. These cases provide a more complete picture of Covid‐19 illness, and are important in the development of effective treatment strategies.

This study concerns the clinicopathologic correlation of 50 decedents of 2019 coronavirus disease (Covid-19) due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) from among 250 reported patients succumbing to Covid-19 illness (1-7) who underwent detailed postmortem neuropathological studies. This disease, which starts in the lungs, is a multisystem disorder affecting all major organs including the brain. These cases provide a more complete picture of Covid-19 illness, and are important in the development of effective treatment strategies.

As shown in Table 1 , older age, male gender, increased serum cytokine and pro-coagulation markers, and critical care hospitalization for ≤10 days prior to death characterized the cohort.

Immediate causes of death were ascribed to cardiopulmonary and multiple organ failure, intracranial hemorrhage and pulmonary embolus. SARS-CoV-2 staining in brain tissue by polymerase chain reaction was negative in all cases. Seventeen (36%) cases showed focal or diffuse cortical, brainstem, or leptomeningeal inflammation, characterized (in five) as T-cell-mediated based upon flow cytometry. A variety of comorbid pathology in 11 cases (22%) included chronic stroke, Alzheimer or Lewy body disease and primary brain tumor.

Eight patients had unsuspected encephalitis affecting predominant subcortical white matter 

This article is protected by copyright. All rights reserved indicative of a cytokine storm. Together with increased serum D-dimer and markers of hypercoagulability in 42% of cases (1, 2) , affected patients risk thrombotic and hemorrhagic parenchymal tissue infarction so noted in nine (18%) cases. Third, eight (16%) cases with ADEMlike features (2, 5) or frank histologic evidence of brainstem encephalitis suggest the need for an index of suspicion in clinically compatible cases.

There were several limitation to this study. First, there was missing data about age, gender and the cause of death in some cases. Second, case series were often small and unselected. Third, among the various studies included, there were often contradictory conclusions about the significance of inflammatory vascular changes in regards to active central nervous system involvement. In this regard, all patients were in a very critical condition necessitating intensive care due to cardiopulmonary and systemic organ failure. In the absence of comparison to controls, it is not possible to know with certainty whether the histopathological findings suggesting inflammatory vasculopathy, in up to a third of cases, were merely nonspecific.

Awaiting randomized, placebo-controlled trials of antiviral therapy to treat severe Covid-19, or a safe and effective vaccine, this small sample adds to the urgent call to identity neuroprotective therapy. Present research focuses on inhibitors of the cytokine storm using the IL-6 receptor antagonist tocilizumab (ClinicalTrials.gov Identifier: NCT04377659) and the anti-IL-6 monoclonal antibody clazakizumab (ClinicalTrials.gov Identifier: NCT04363502).

Pathophysiology of SARS-Cov-2: targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience

Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology

Early evidence of pronounced brain involvement in fatal COVID-19 outcomes

Neuropathological Features of Covid-19

Neuronophagia and microglial nodules in a SARS-CoV-2 patient with cerebellar hemorrhage

Neuropathologic features of four autopsied COVID-19 patients

The spectrum of pathological findings in coronavirus disease (COVID-19) and the pathogenesis of SARS-CoV-2

This article is protected by copyright. All rights reserved