key: cord-0697782-vps02v8p authors: Lopez, Gianluca; Tonello, Cristina; Osipova, Ganna; Carsana, Luca; Biasin, Mara; Cappelletti, Gioia; Pellegrinelli, Alessandro; Lauri, Eleonora; Zerbi, Pietro; Rossi, Roberta Simona; Nebuloni, Manuela title: Olfactory bulb SARS‐CoV‐2 infection is not paralleled by the presence of virus in other central nervous system areas date: 2021-08-09 journal: Neuropathol Appl Neurobiol DOI: 10.1111/nan.12752 sha: 793dd02d14c544d28aa6fb854427b48d55759278 doc_id: 697782 cord_uid: vps02v8p nan The ongoing SARS-CoV-2 pandemic has proven to be challenging, in both clinical and pathological terms. The viral tropism for angiotensinconverting enzyme 2 (ACE-2) receptor-expressing cells is paralleled in the clinical setting by the development of a spectrum of manifestations, most notably acute respiratory distress syndrome (ARDS). [1] [2] [3] Neurological symptoms are frequent in COVID-19 patients; however, central nervous system (CNS) infection and subsequent neurological disease attributable to SARS-CoV-2 remains a still poorly defined topic. 4, 5 Both glial and neuronal cells have demonstrated ACE-2 expression and are therefore susceptible to SARS-CoV-2 infection. [6] [7] [8] Moreover, the possible spread of the virus through olfactory nerve fibres to the CNS remains an interesting although elusive issue. 9 A number of post-mortem neuropathological studies have reported vascular, thrombotic, and ischaemic alterations in COVID-19 cases. [10] [11] [12] [13] [14] [15] [16] Of note, the presence of SARS-CoV-2 within CNS specimens was reported to range between 0% and 53% of analysed cases across studies, including the olfactory bulbs and/or cerebral parenchyma. [12] [13] [14] [15] [16] Our group aimed to describe the neuropathological findings in SARS-CoV-2 infected patients who died during the COVID-19 pandemic and, by using real-time (RT) PCR and immunohistochemistry The entire brain was fixed in neutral-buffered formalin for a minimum of 21 days (range 21-42 days). Macroscopic examination and sampling were performed by cutting the brain in the coronal plane at level of the mammillary bodies and then sectioning at 1 cm intervals in order to comprehensively evaluate brain parenchyma and related structures. An extensive sampling of the brain was performed, which included areas from cervical spinal cord, brain stem (medulla oblongata, pons and midbrain), cerebellar hemispheres (cortex and dentate nuclei), cerebral hemispheres (frontal, parietal, temporal, and occipital cortex; hippocampus with entorhinal cortex, basal ganglia, thalamus, hypothalamus, amygdala, olfactory tubercles with medial and lateral olfactory tracts), and olfactory bulbs. Other organs, that is, lungs, heart, liver, kidneys, spleen, and bowel, were extensively sampled for diagnostic purposes and were routinely examined. Our results are summarised in Table 1 The natural history, pathobiology, and clinical manifestations of SARS-CoV-2 infections Acute respiratory failure in COVID-19: is it "typical Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain SARS-CoV-2 infects human neural progenitor cells and brain organoids Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and glial cells: Insights and perspectives Involvement of the nervous system in SARS-CoV-2 infection Neuroinvasion, neurotropic, and neuroinflammatory events of SARS-CoV-2: understanding the neurological manifestations in COVID-19 patients Potential neuroinvasive pathways of SARS-CoV-2: deciphering the spectrum of neurological deficit seen in coronavirus disease-2019 (COVID-19) Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19 Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19 Brain ischemic injury in COVID-19-infected patients: a series of 10 post-mortem cases Neuropathological features of Covid-19 Unspecific postmortem findings despite multiorgan viral spread in COVID-19 patients Neuropathology of patients with COVID-19 in Germany: a post-mortem case series Neuropathologic features of four autopsied COVID-19 patients Human astrocytes in the diseased brain Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19 The consequences of coronavirus-induced cytokine storm are associated with neurological diseases, which may be preventable Arterial supply of the upper cranial nerves: a comprehensive review Olfactory bulb SARS-CoV-2 infection is not paralleled by the presence of virus in other central nervous system areas The authors would like to thank all laboratory technicians and administrative staff of the Pathology Unit, L. Sacco Hospital, Milan, Italy, for their support. The authors declare no conflict of interests. The Ethics Committee of Luigi Sacco Hospital approved the use of patient data for scientific research related to the disease. This study followed the Italian general rules used for scientific research purposes (regulation no. 72-26/03/2012). GL was responsible for the original draft preparation, data collection and curation, and final draft preparation; CT, GO, EL, MB, and GC were responsible for the data collection and curation; LC, AP, and RSR performed autopsies; PZ performed autopsies and was responsible for the data collection and curation; MN performed autopsies and was responsible for the supervision, data collection and curation, and final draft preparation. All authors approved the final version of the manuscript. The data that support the findings of this study are available from the corresponding author upon reasonable request. https://orcid.org/0000-0002-9262-1212