ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) commonly results in a respiratory illness in symptomatic patients; however, those critically ill can develop a leukoencephalopathy. We describe two patients who had novel subacute MRI findings in the context of coronavirus disease 2019 (COVID-19) leukoencephalopathy, which we hypothesize could implicate a potent small-vessel vasculitis, ischemic demyelination and the presence of prolonged ischemia. Recent evidence of the direct neuroinvasiness of SARS-CoV-2 leading to ischemia and vascular damage supports this hypothesis.
Subject(s)
COVID-19/complications , Demyelinating Diseases/pathology , Leukoencephalopathies/pathology , Leukoencephalopathies/virology , Vasculitis, Central Nervous System/pathology , Demyelinating Diseases/virology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , SARS-CoV-2 , Vasculitis, Central Nervous System/virologySubject(s)
COVID-19/pathology , Cranial Nerves/pathology , Polyneuropathies/pathology , Polyneuropathies/therapy , Anemia, Sickle Cell/complications , Child , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/drug therapy , Febrile Neutropenia/complications , Febrile Neutropenia/drug therapy , Female , Hematopoietic Stem Cell Transplantation/methods , Herpes Simplex/complications , Herpes Simplex/drug therapy , Humans , Mucositis/complications , Mucositis/drug therapy , Polyneuropathies/virology , SARS-CoV-2 , Vasculitis, Central Nervous System/pathologyABSTRACT
Coronavirus disease 19 (COVID-19) is a rapidly evolving pandemic caused by the coronavirus Sars-CoV-2. Clinically manifest central nervous system symptoms have been described in COVID-19 patients and could be the consequence of commonly associated vascular pathology, but the detailed neuropathological sequelae remain largely unknown. A total of six cases, all positive for Sars-CoV-2, showed evidence of cerebral petechial hemorrhages and microthrombi at autopsy. Two out of six patients showed an elevated risk for disseminated intravascular coagulopathy according to current criteria and were excluded from further analysis. In the remaining four patients, the hemorrhages were most prominent at the grey and white matter junction of the neocortex, but were also found in the brainstem, deep grey matter structures and cerebellum. Two patients showed vascular intramural inflammatory infiltrates, consistent with Sars-CoV-2-associated endotheliitis, which was associated by elevated levels of the Sars-CoV-2 receptor ACE2 in the brain vasculature. Distribution and morphology of patchy brain microbleeds was clearly distinct from hypertension-related hemorrhage, critical illness-associated microbleeds and cerebral amyloid angiopathy, which was ruled out by immunohistochemistry. Cerebral microhemorrhages in COVID-19 patients could be a consequence of Sars- CoV-2-induced endotheliitis and more general vasculopathic changes and may correlate with an increased risk of vascular encephalopathy.