2023-10-27 14:36:17
The appearance of different variants of SARS-CoV-2 has brought out variability in clinical profiles and symptoms among patients. For the first time, researchers from the Pasteur Institute and Paris Cité University have demonstrated, in an animal model, a characteristic common to several variants of SARS-CoV-2: the ability to infect the nervous system central. The study also confirms that SARS-CoV-2 is capable of infecting human neurons in vitro, and to move inside the axons, the extensions of the nerve cell which conduct information. These results were published on July 26, 2023 in the journal Nature Communications.
The neurological symptoms associated with SARS-Cov-2 infection have changed during the evolution of the virus and the appearance of new variants. If at the start of the Covid-19 pandemic, anosmia was identified as one of the characteristic symptoms of an infection, this same symptom was found to be less frequent with infections with the Omicron/BA.1 variant. Is the variability of symptoms a sign of a more or less strong affinity of SARS-CoV-2 for the nervous system?
In this study, researchers from the Pasteur Institute and Paris Cité University showed in an animal model that a panel of variants of interest in SARS-CoV-2 (the original strain of the virus, detected for the first time in Wuhan and the Gamma, Delta and Omicron/BA.1) variants can access the central nervous system and are localized there during the acute phase of infection.
Scientists have observed that all these variants invade the central nervous system and infect the olfactory bulbs, a structure located in the cranium which processes olfactory information and transmits it to the cortex. “ In this study, we show that the infection of the olfactory bulbs is systematic and is not linked to a particular variant, nor to a particular clinical manifestation, such as loss of smell for example.. » explains Guilherme Dias de Melo, first author of the study and researcher in the Lyssavirus, epidemiology and neuropathology unit at the Pasteur Institute. Researchers have also identified in the ancestral virus (Wuhan), a genetic sequence linked to anosmia. When this genetic sequence, coding for the ORF7ab protein, is deleted or truncated as in certain variants in which anosmia is less present, the incidence of loss of olfaction in infected animals is reduced without modifying neuroinvasion via the olfactory bulbs. “ This tends to prove that anosmia and neuronal infection are two uncorrelated phenomena. » indicate Guilherme Dias de Melo. « It is entirely possible, if we follow this reasoning, that an infection, even asymptomatic – and therefore clinically benign – is characterized by diffusion of the virus in the nervous system.. »
The scientists then sought to understand how SARS-CoV-2 manages to reach the olfactory bulbs, with neurons appearing to be an ideal route. A microfluidic cell culture system in vitro allowed them to obtain human neurons organized in a particular way. The neurons are thus oriented so as to be able to closely observe the transport of molecules inside the axon.[1].
Using this method, scientists found that once inside the neuron, the virus is able to move in both directions of the axon [1] : in the anterograde direction, that is to say from the cell body towards the terminals of the axon, or in the retrograde direction, from the axons towards the cell body. “ The virus appears to effectively exploit the neuron’s physiological mechanisms to move in both directions. The SARS-CoV-2 variants that we studied, Wuhan ancestral variant, Gamma, Delta and Omicron/BA.1, infect neurons in vitro and are capable of moving along axons ».
« Through this study, we characterized the neurotropism of SARS-CoV-2. For all variants studied, brain infection via the olfactory bulbs appears to be a common characteristic of SARS-CoV-2 » concludes Hervé Bourhy, last author of the study and head of the Lyssavirus, epidemiology and neuropathology unit at the Institut Pasteur. “ The next step will be to understand, in the animal model, whether the virus is capable of persisting in the brain beyond the acute phase of infection and whether the presence of the virus can induce persistent inflammation and cause the persistent symptoms described. in cases of long Covid, such as anxiety, depression and brain fog. »
This work was funded by the organizations cited above, as well as the FRM, ANRS-MIE and Human Brain Project.
[1] Each neuron has an axon, a single, thin extension of the cell, which carries the electrical signal to the next cell (neuron or muscle).
Source :
Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants, Nature Communications, July 26, 2023
Guilherme Dias de Melo1Victoire Perraud1§Flavio Alvarez2,3§Alba Vieites-Prado4§Seonhee Kim1Lauriane Kergoat1Anthony Coleon1Bettina Salome Trüeb5Magali Tichit6Aurèle Piazza7Agnès Thierry7David Hardy6Nicolas Wolff2Sandie Munier8Romain Koszul7Etienne Simon-Lorière9Volker Thiel10Marc Lecuit11,12Pierre-Marie Lledo13Nicolas Renier4Florence Larrous1#Hervé Bourhy1#*
1 Pasteur Institute, Paris Cité University, Lyssavirus Epidemiology and Neuropathology Unit, F-75015 Paris, France
2 Pasteur Institute, Paris Cité University, Channel Receptors Unit, F-75015 Paris, France
3 Sorbonne University, Doctoral College, F-75005 Paris, France
4 Brain and Spinal Cord Institute, Structural Plasticity Laboratory, Sorbonne University, INSERM U1127, CNRS UMR7225, 75013 Paris, France
5 Institute of Virology and Immunology (IVI), Bern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
6 Pasteur Institute, Paris Cité University, Histopathology Platform, F-75015 Paris, France
7 Pasteur Institute, Paris Cité University, Spatial Regulation of Genomes Laboratory, F-75015 Paris, France
8 Institut Pasteur, Université Paris Cité, Molecular Genetics of RNA viruses Unit, F-75015 Paris, France
9 Institut Pasteur, Université Paris Cité, Evolutionary Genomics of RNA Viruses Group, F-75015 Paris, France
10 Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland
11 Pasteur Institute, Paris Cité University, Inserm U1117, Biology of Infection Unit, 75015 Paris, France
12 Necker-Enfants Malades University Hospital, Division of Infectious Diseases and Tropical Medicine, APHP, Institut Imagine, 75006, Paris, France
13 Pasteur Institute, Paris Cité University, Perception and Memory Unit, F-75015 Paris, France; CNRS UMR3571, 75015 Paris, France
§ These authors contributed equally
# These authors share senior authorship
* Corresponding author
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