Dödligt virus från Kina orsakar panik (SARS-CoV-2, COVID-19)

SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer's-like neuropathology
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Abstract

Major cell entry factors of SARS-CoV-2 are present in neurons; however, the neurotropism of SARS-CoV-2 and the phenotypes of infected neurons are still unclear. Acute neurological disorders occur in many patients, and one-third of COVID-19 survivors suffer from brain diseases. Here, we show that SARS-CoV-2 invades the brains of five patients with COVID-19 and Alzheimers, autism, frontotemporal dementia or no underlying condition by infecting neurons and other cells in the cortex. SARS-CoV-2 induces or enhances Alzheimers-like neuropathology with manifestations of beta-amyloid aggregation and plaque formation, tauopathy, neuroinflammation and cell death. SARS-CoV-2 infects mature but not immature neurons derived from inducible pluripotent stem cells from healthy and Alzheimers individuals through its receptor ACE2 and facilitator neuropilin-1. ... Thus, SARS-CoV-2 invades the brain and activates an Alzheimers-like program.

Introduction

... SARS-CoV-2 not only causes respiratory syndromes but also leads to neurological abnormalities, with an 85% occurrence rate in patients with Alzheimer’s disease. In fact, neurological symptoms, including hypogeusia, headache and anosmia, precede the onset of respiratory symptoms in the majority of patients with COVID-19. The major chronic sequelae of COVID-19 are expected to be cognitive decline and dementia. A recent study has shown that one-third of COVID-19 survivors exhibit substantial neurological and psychiatric morbidity in the 6 months after SARS-CoV-2 infection. Furthermore, the “brain disease” risk is not limited to patients who have severe COVID-19. ...

It has been proposed that β-coronaviruses, including SARS-CoV-2, can invade the central nervous system. The two coronaviruses closely related to SARS-CoV-2, Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), can infect the central nervous system. A recent study showed the presence of SARS-CoV-2 in a patient’s olfactory mucosa and its neuronal projections. ... However, neurological disorders are not limited to severe COVID-19 cases, suggesting that multiple brain entries may account for SARS-CoV-2 neurotropism. Although SARS-CoV-2 can enter the brain, experimental evidence of its presence in key brain regions involved in cognitive functions is still lacking, and little is known about the functional impact of SARS-CoV-2 CNS invasion on neurons.

... This evidence implicates either the existence of other cell surface receptors in SARS-CoV-2 cell entry or the facilitation of cell entry by other factors. Indeed, neuropilin-1 (NRP1) has been identified as a facilitator of SARS-CoV-2 entry when ACE2 is expressed, leading to high rates of infection. ... NRP1 is abundantly expressed in cells of many tissues including neurons. The presence of ACE2 and NRP1 in neurons suggests the high possibility of neurotropism. ...

There is a profound link between SARS-CoV-2 infection and dementia/Alzheimer’s disease. The 2002 and 2012 SARS and MERS epidemics caused memory impairment in many recovered patients. Neurological syndromes related to Alzheimer’s disease, including neuroinflammatory syndromes, seizures, delirium, and alterations in personality, behavior, and cognitive deficits, frequently occur in patients with COVID-19 who recover from COVID-19. Thus, SARS-CoV-2 infection of the brain may increase the risk of Alzheimer’s disease. ...

In this study, we sought to test whether SARS-CoV-2 is neurotropic and infects neural cells in the cognitive center in five patients with Alzheimer’s disease, autism, frontotemporal dementia and no underlying condition, respectively. ... We found that SARS-CoV-2 invades the cognitive centers of all five COVID-19 patients, leading to Alzheimer’s-like neuropathology or Alzheimer’s neuropathology exacerbation. SARS-CoV-2 infects human inducible pluripotent stem cell (iPSC)-derived mature neurons from healthy individuals, leading to amyloid beta (Aβ) deposition, increased inflammation, neuronal death and increased expression of Alzheimer’s mediators. ...