The olfactory nerve is not a likely route to brain infection in COVID-19: a critical review of data from humans and animal models

Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier?

(2021) Susan M. Burks et al.   BRAIN BEHAVIOR AND IMMUNITY

Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb

(2021) Moritz Klingenstein et al.   CELLS TISSUES ORGANS

Neuroinvasion of SARS-CoV-2 in human and mouse brain

(2021) Eric Song et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Neurological infection with SARS-CoV-2 — the story so far

(2021) Tom Solomon   Nature Reviews Neurology

Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice

(2021) Pratima Kumari et al.   Viruses-Basel

Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection

(2021) Helen E. Everett et al.   Viruses-Basel

K18-hACE2 mice develop respiratory disease resembling severe COVID-19

(2021) Claude Kwe Yinda et al.   PLoS Pathogens

Regeneration Profiles of Olfactory Epithelium after SARS-CoV-2 Infection in Golden Syrian Hamsters

(2021) Shinji Urata et al.   ACS Chemical Neuroscience

Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity

(2021) Daisy A. Hoagland et al.   IMMUNITY

Potential differences in cleavage of the S protein and type-1 interferon together control human coronavirus infection, propagation, and neuropathology within the central nervous system

(2021) Alain Le Coupanec et al.   JOURNAL OF VIROLOGY

Infection Mechanism of SARS-COV-2 and Its Implication on the Nervous System

(2021) Edwin Estefan Reza-Zaldívar et al.   Frontiers in Immunology

The neuroinvasive potential of SARS‐CoV2 may be at least partially responsible for the respiratory failure of COVID‐19 patients

(2020) Yan‐Chao Li et al.   JOURNAL OF MEDICAL VIROLOGY

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

(2020) Lirong Zou et al.   NEW ENGLAND JOURNAL OF MEDICINE

Is the Collapse of the Respiratory Center in the Brain Responsible for Respiratory Breakdown in COVID-19 Patients?

(2020) Sonu Gandhi et al.   ACS Chemical Neuroscience

Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in Cells of the Olfactory Epithelium: Identification of Cell Types and Trends with Age

(2020) Katarzyna Bilinska et al.   ACS Chemical Neuroscience

SARS-CoV-2: Olfaction, Brain Infection, and the Urgent Need for Clinical Samples Allowing Earlier Virus Detection

(2020) Rafal Butowt et al.   ACS Chemical Neuroscience

Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2

(2020) Ren-Di Jiang et al.   CELL

SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

(2020) Yixuan J. Hou et al.   CELL

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues

(2020) Carly G.K. Ziegler et al.   CELL

A Mouse Model of SARS-CoV-2 Infection and Pathogenesis

(2020) Shi-Hui Sun et al.   Cell Host & Microbe

Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility

(2020) Jasper Fuk-Woo Chan et al.   CLINICAL INFECTIOUS DISEASES

Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models

(2020) S. Natoli et al.   EUROPEAN JOURNAL OF NEUROLOGY

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

(2020) Wenling Wang et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Pathogenesis and transmission of SARS-CoV-2 in golden hamsters

(2020) Sin Fun Sia et al.   NATURE

Respiratory disease in rhesus macaques inoculated with SARS-CoV-2

(2020) Vincent J. Munster et al.   NATURE

The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice

(2020) Linlin Bao et al.   NATURE

Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model

(2020) Barry Rockx et al.   SCIENCE

Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019

(2020) Adeel S. Zubair et al.   JAMA Neurology

Sustentacular Cell Enwrapment of Olfactory Receptor Neuronal Dendrites: An Update

(2020) Fengyi Liang   Genes

Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain

(2020) Zhengqian Li et al.   Frontiers of Medicine

Anosmia in COVID-19: A Bumpy Road to Establishing a Cellular Mechanism

(2020) Katarzyna Bilinska et al.   ACS Chemical Neuroscience

Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

(2020) Bertrand Bryche et al.   BRAIN BEHAVIOR AND IMMUNITY

A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies

(2020) Ahmed O. Hassan et al.   CELL

SARS-CoV-2 infects and damages the mature and immature olfactory sensory neurons of hamsters

(2020) Anna Jinxia Zhang et al.   CLINICAL INFECTIOUS DISEASES

Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms

(2020) Bernhard Neumann et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

Neurological associations of COVID-19

(2020) Mark A Ellul et al.   LANCET NEUROLOGY

COVID-19 and the Chemical Senses: Supporting Players Take Center Stage

(2020) Keiland W. Cooper et al.   NEURON

Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development

(2020) Masaki Imai et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes

(2020) Matteo Briguglio et al.   Frontiers in Physiology

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

(2020) David H. Brann et al.   Science Advances

Central Nervous System Targets and Routes for SARS-CoV-2: Current Views and New Hypotheses

(2020) Francisco J. Barrantes   ACS Chemical Neuroscience

Prevalence of Chemosensory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis Reveals Significant Ethnic Differences

(2020) Christopher S. von Bartheld et al.   ACS Chemical Neuroscience

The Cellular basis of loss of smell in 2019-nCoV-infected individuals

(2020) Krishan Gupta et al.   BRIEFINGS IN BIOINFORMATICS

A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice

(2020) Sarah R. Leist et al.   CELL

SARS-CoV-2 infects the brain choroid plexus and disrupts the blood-CSF-barrier in human brain organoids

(2020) Laura Pellegrini et al.   Cell Stem Cell

Elevated ACE-2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication

(2020) Mengfei Chen et al.   EUROPEAN RESPIRATORY JOURNAL

Hunting coronavirus by transmission electron microscopy – a guide to SARS‐CoV‐2‐associated ultrastructural pathology in COVID‐19 tissues

(2020) Helmut Hopfer et al.   HISTOPATHOLOGY

Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS‐CoV‐2 infection

(2020) Jia‐Mei Liu et al.   JOURNAL OF MEDICAL VIROLOGY

Neuroinvasion of SARS‐CoV‐2 may play a role in the breakdown of the respiratory center of the brain

(2020) Jhilik Dey et al.   JOURNAL OF MEDICAL VIROLOGY

Multiple Neuroinvasive Pathways in COVID-19

(2020) Dmitri Bougakov et al.   MOLECULAR NEUROBIOLOGY

Animal models for COVID-19

(2020) César Muñoz-Fontela et al.   NATURE

SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function

(2020) Emma S. Winkler et al.   NATURE IMMUNOLOGY

Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection

(2020) Rafal Butowt et al.   NEUROSCIENTIST

Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates

(2020) Joana Damas et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

(2020) Ludovico Cantuti-Castelvetri et al.   SCIENCE

Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques

(2020) Wei Deng et al.   Nature Communications

Histological Evidence for the Enteric Nervous System and the Choroid Plexus as Alternative Routes of Neuroinvasion by SARS-CoV2

(2020) Felix Deffner et al.   Frontiers in Neuroanatomy

SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and shedding of infectious virus from both respiratory and gastrointestinal tracts

(2020) Amy L. Hartman et al.   PLoS Pathogens

Comparison of Transgenic and Adenovirus hACE2 Mouse Models for SARS-CoV-2 Infection

(2020) Raveen Rathnasinghe et al.   Emerging Microbes & Infections

Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease

(2020) Joseph W. Golden et al.   JCI Insight

Rapidly Deployable Mouse Models of SARS-CoV-2 Infection Add Flexibility to the COVID-19 Toolbox

(2020) James A. Harker et al.   AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

(2020) Jenny Meinhardt et al.   NATURE NEUROSCIENCE

The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice

(2020) Elizabeth M. Rhea et al.   NATURE NEUROSCIENCE

What can we learn from brain autopsies in COVID-19?

(2020) Shibani S. Mukerji et al.   NEUROSCIENCE LETTERS

Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice

(2020) Fatai S. Oladunni et al.   Nature Communications

SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication

(2020) Soren Alexandersen et al.   Nature Communications

SARS-CoV-2 Is Not Detected in the Cerebrospinal Fluid of Encephalopathic COVID-19 Patients

(2020) Dimitris G. Placantonakis et al.   Frontiers in Neurology

SARS-CoV-2 Receptors and Entry Genes Are Expressed in the Human Olfactory Neuroepithelium and Brain

(2020) Leon Fodoulian et al.   iScience

Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein

(2020) Gerard J. Nuovo et al.   Annals of Diagnostic Pathology

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

(2019) Marc Desforges et al.   Viruses-Basel

Olfactory receptor neuronal dendrites become mostly intra-sustentacularly enwrapped upon maturity

(2018) Fengyi Liang   JOURNAL OF ANATOMY

Axonal Transport Enables Neuron-to-Neuron propagation of HCoV-OC43

(2018) Mathieu Dubé et al.   JOURNAL OF VIROLOGY

CNS infection and immune privilege

(2018) John V. Forrester et al.   NATURE REVIEWS NEUROSCIENCE

5HTR3A-driven GFP labels immature olfactory sensory neurons

(2017) Thomas E. Finger et al.   JOURNAL OF COMPARATIVE NEUROLOGY

Axonal spread of neuroinvasive viral infections

(2015) Matthew P. Taylor et al.   TRENDS IN MICROBIOLOGY

Specialized Cilia in Mammalian Sensory Systems

(2015) Nathalie Falk et al.   Cells

The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system

(2014) Debby van Riel et al.   JOURNAL OF PATHOLOGY

Age-related changes in cell dynamics of the postnatal mouse olfactory neuroepithelium: Cell proliferation, neuronal differentiation, and cell death

(2010) Kenji Kondo et al.   JOURNAL OF COMPARATIVE NEUROLOGY

The olfactory vector hypothesis of neurodegenerative disease: Is it viable?

(2008) Richard L. Doty   ANNALS OF NEUROLOGY