ABSTRACT
Introduction: Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease which is accompanied by a broad spectrum of neurological manifestations in more than one-third of COVID-19 cases. For the latter, olfactory and gustatory disturbances such as anosmia and ageusia, are often leading symptoms of SARS-CoV-2 infection. Given the close proximity of neuronal and supporting cells the olfactory mucosa as a neural-mucosal interface may represent a potential port of CNS entry for SARS-CoV-2. Objectives: Identifying potential sites of SARS-COV-2 CNS entry and morphological changes associated with SARS-CoV-2 infection. Methods: We systematically investigated postmortem tissue of the CNS and nasopharynx from 75 individuals with COVID-19. Based on the correlation of clinical data and (neuro-) pathological examinations, SARSCoV- 2-specific morphological changes were determined. Using quantitative real-time PCR, RNAscope in situ hybridization, immunohistochemistry and electron microscopy, we characterized the CNS tropism of SARSCoV- 2 and the consequences thereof. Results: Acute thromboembolic ischemic infarcts (n = 10/64) and a strong innate immune response, mediated by HLA-DR+ microglia with a linked increase in proinflammatory mediators in the cerebrospinal fluid, are leading alterations in the CNS. Besides, a distinct immunoreactivity for SARSCoV Spike protein was found in the olfactory epithelium - here co-localizing with neural/neuronal cells - and cerebral endothelial cells. We were also able to illustrate intact coronavirus particles in the olfactory mucosa ultrastructurally. Conclusion: SARSCoV- 2 can enter the nervous system by crossing the neural-mucosal interface in the olfactory mucosa. SARSCoV- 2 infection results in an innate immune response with activation of HLA-DR+ microglia and increased levels of inflammatory mediators in the CNS.
ABSTRACT
The health effects of coronavirus disease 2019 (COVID-19) caused by the infection of SARS-CoV2 (severe acute respiratory syndrome coronavirus 2) are becoming increasingly clear as the pandemic spreads. In addition to the lungs, other organs are also affected, which can significantly influence morbidity and mortality. In particular, neurological symptoms involving the central nervous system can lead to acute or long-term consequences. The mechanisms of this neuropathogenesis of SARS-CoV2 infection and its relation to acute and chronic neurological symptoms are the subject of current studies investigating a potential direct and indirect viral infection of the nervous system. The following review summarizes the current status of neuropathological manifestations, molecular pathogenesis, possible infection pathways in the nervous system, and systemic effects. In addition, an overview of the Germany-wide CNS-COVID19 registry and collaborations is presented, which should contribute to a better understanding of the neurological symptoms of COVID-19.