Neuroinvasive potential of SARS‐CoV2 with neuroradiological and neuropathological findings: is the brain a target or a victim?

Abstract

Coronaviridae family includes pathogen viruses for humans, that lead to clinical conditions with main respiratory involvement; many of these viruses have notoriously a neuroinvasive potential, as demonstrated by published data on SARS‐CoV and MERS‐CoV epidemics, as well by results obtained in experimental models. During pandemic of coronavirus disease 2019 (COVID‐19), it is noticed that the central nervous system involvement represented a truly significant moment in the history of some COVID‐19 patients; indeed, clinical and radiological features published in literature regarding COVID‐19 disease are consistent with a neurological involvement. It is also known that histopathological data related to SARS‐CoV2 infection have been published with considerable delay, which was even greater for neuropathological information. Moreover, many published data are incomplete, and often the lesions described are not directly related to the action of the virus. In this review, we collected the available radiological and neuropathological information, in order to delineate a more complete picture of the relationship between SARS‐Cov2 and brain, focusing our attention on the two most important neuroinvasion routes for the virus. We also highlighted what we consider methodological mistakes both in the autopsy procedures and brain study in COVID‐19 deaths. We emphasize the need for a complete study of all the organs in case of autopsy. It is important that through this experience, we no longer do the mistake of neglecting the brain.

Neuropathologic findings of patients with COVID-19: a systematic review

“…In this sense, the virus could penetrate the CNS through the neuroepithelium of the olfactory mucosa to reach the olfactory bulb, gain access to the mitral cells and the olfactory nerve, and then spread to adjacent areas of the brain such as the hippocampus and other brain structures [53,54]. This route was demonstrated in mice with intracranially inoculated SARS-CoV-1 and was supported by anosmia as one of the early symptoms in COVID-19 infection [3,5,54]. As previously mentioned, ACE2 and TMPRSS2 have been detected in the nasal mucosa; however, reports demonstrated that they are rather localized to epithelial cells (sustentacular cells) and not in the olfactory neurons [55].…”

“…Coronavirus disease 2019 (COVID- 19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [2]. Although the involvement of the respiratory system is the most relevant clinical feature in COVID-19 patients, systematic reviews with meta-analysis demonstrate that the spectrum of clinical presentations is wider [3]. It has been reported that some severely affected patients experience neurological symptoms like headache, dizziness, and impaired sensorium while recent reports have noted that anosmia, ageusia, ataxia, and seizures may be early signs and symptoms in SARS-CoV-2-infected patients, suggesting that this virus may also be neurotropic [3][4][5][6].…”

“…Although the involvement of the respiratory system is the most relevant clinical feature in COVID-19 patients, systematic reviews with meta-analysis demonstrate that the spectrum of clinical presentations is wider [3]. It has been reported that some severely affected patients experience neurological symptoms like headache, dizziness, and impaired sensorium while recent reports have noted that anosmia, ageusia, ataxia, and seizures may be early signs and symptoms in SARS-CoV-2-infected patients, suggesting that this virus may also be neurotropic [3][4][5][6]. In a recent study, it was found that 36.4% COVID- 19 of patients presented with central nervous system (CNS) symptoms, 8.9% with peripheral nervous symptoms, and 10.7% with skeletal muscle symptoms [4].…”

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

“…Another relevant concern regards the sampling. It is often unclear if it has been sufficient and if standard protocols have been adopted; therefore, the microscopic results obtained may not be comparable [47]. Furthermore, data appear to be heterogeneous since only a few papers have identified the virus with the reverse transcription-quantitative polymerase chain reaction (RT-qPCR).…”

“…Furthermore, data appear to be heterogeneous since only a few papers have identified the virus with the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Even when the assay was executed, it is also uncertain whether the genome could be exclusively identified with that of SARS-CoV-2 [47].…”