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

Abstract

We document the neuropathologic findings of a 73-year old man who died from acute cerebellar hemorrhage in the context of relatively mild SARS-CoV2 infection. The patient developed sudden onset of headache, nausea, and vomiting, immediately followed by loss of consciousness on the day of admission. Emergency medical services found him severely hypoxemic at home, and the patient suffered a cardiac arrest during transport to the emergency department. The emergency team achieved return of spontaneous circulation after over 17 min of resuscitation. A chest radiograph revealed hazy bilateral opacities; and real-time-PCR for SARS-CoV-2 on the nasopharyngeal swab was positive. Computed tomography of the head showed a large right cerebellar hemorrhage, with tonsillar herniation and intraventricular hemorrhage. One day after presentation, he was transitioned to comfort care and died shortly after palliative extubation. Autopsy performed 3 h after death showed cerebellar hemorrhage and acute infarcts in the dorsal pons and medulla. Remarkably, there were microglial nodules and neuronophagia bilaterally in the inferior olives and multifocally in the cerebellar dentate nuclei. This constellation of findings has not been reported thus far in the context of SARS-CoV-2 infection.

Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS‐CoV‐2 infection

“…In the study reported by Solomon et al 46 and the study by Al‐Dalahmah et al, 48 the positive PCR results for SARS‐CoV‐2 in the CNS have not been confirmed in the same brain areas by immunostaining or in situ hybridization. In the study of Remmelink et al, 47 although SARS‐CoV‐2 RNA was found in 9 of 11 cerebral samples, autopsy examination did not found evidence of viral encephalitis or vasculitis.…”

“…Up to September 14, 2020, a total of 20 autopsy studies on neuropathology were retrieved, among which CNS detection of SARS‐CoV‐2 was negative in 12 (of 12) cases from three studies, 36,42,43 and positive in 58 (of 87) cases (66.7%) from nine studies, 46‐54 and unavailable for 109 cases in eight studies 35,37‐41,44,45 …”

“…On June 12, 2020, Solomon et al 46 In the study reported by Solomon et al 46 and the study by Al-Dalahmah et al, 48 Electron microscopic observations showed that the virus could utilize host cell machinery to replicate in the neurons. In addition, SARS-CoV-2 infection has been found in radial glia and neuronal progenitor cells.…”

Neurological Sequelae in Patients with COVID-19: A Histopathological Perspective

“…Based on the clinical studies and the limited neuropathological data, CNS histopathology encompasses hypoxic/ischemic encephalopathy, activated microglial cells with variable infiltration of perivascular T lymphocyte, cerebrovascular diseases, AHNE, encephalitis/meningitis, acute myelitis, demyelinating disorders, and PNS involvement [ 21 , 68 , 71 , 73 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 ], with histologically documented lesions in some studies [ 6 , 11 , 68 , 69 , 71 , 72 , 73 ].…”

“…Since demyelination is usually caused by the autoimmune reaction triggered by an excessive and widespread inflammation [ 72 ], there are also findings of demyelinating lesions induced by SARS-CoV and associated with MS earlier in the pandemic. However, one case only histologically documented neuronal damage with perivascular lymphocytes and microglial reaction, associated with the CD68+ histiocytic population more represented than lymphocytes [ 71 ]. Moreover, pathological correlates are not strong, thus requiring more and systematic investigations in this “cutting-edge” topic.…”